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\"In her humorous and emotionally resonant debut, Emma Smith-Stevens follows the exploits and evolution of a young man - known only as \"the Australian\" - over the course of a dozen years, from his time posing for tourist photos as Superman to his life in New York, chasing fame and fortune. Married to a woman he barely knows and struggling to forge a relationship with his son, the Australian travels between the U.S. and Melbourne, seeking to reconnect with his deceased parents through his father's Australian Outdoor Geographic magazines and the Dreaming Tracks, sacred landmarks his mother longed to explore. Through this quest for self-discovery, the Australian becomes both more and less enigma: \"the idea of this guy you could find in any city, a hostel anywhere in the world, smiling, suntanned, hauling a backpack.\" A poignant and at times satirical meditation on masculinity, fatherhood, isolation, New York City, fame, and loss, The Australian examines the human tendency to fall in love with the idea of another person and the importance of knowing one's essential nature\" -- Provided by publisher.

Monitoring alien species is critical to their management. However, early detection of invading alien freshwater fish can be challenging due to the difficulty of observing fish in low abundance. Environmental DNA (eDNA) has emerged as a new and potentially more sensitive method for sampling invasive species as compared to conventional methods, but the comparative financial cost is not often assessed. Adoption of eDNA by managers requires studies that showcase its cost‐effectiveness relative to conventional approaches. Here we use eDNA to assist in the management of an aggressive alien fish, the pearl cichlid (Geophagus brasiliensis), that is invading an urban river in south‐western Australia. We applied an occupancy model to survey data collected 6 years apart (2015, 2021) to assess how the species' distribution had changed and to evaluate whether an instream barrier had the potential to limit upstream invasion. To understand the effectiveness of eDNA, we used our model to quantify the relative efficiency (capture probability) of two eDNA sampling methods (active eDNA and passive eDNA) and fyke netting, as well as the number of replicate samples required per site to deliver >95% detection. We coupled the number of replicates needed with the cost per replicate to determine the cost‐efficiency of each method. We found that G. brasiliensis abundance was higher in downstream reaches in both survey years, and there was no evidence that its distribution had changed through time. However, G. brasiliensis was present above the instream barrier. Active eDNA sampling was considerably better at detecting G. brasiliensis than the other methods, making it the most cost‐effective method. Fyke nets came in a close second, and passive eDNA was a very distant third. Our results directly inform management in the study river and broadly highlight the cost‐effectiveness of active eDNA as a freshwater biosecurity tool. Early detection of invading alien freshwater fish can be challenging due to the difficulty observing fish in low abundance. To understand the effectiveness of eDNA sampling, we used our model to quantify the relative efficiency of two eDNA sampling methods (active eDNA, passive eDNA) and fyke netting as well as the number of replicate samples required per site to deliver >95% detection. Active eDNA sampling was considerably better at detecting an invading fish than the other methods making it the most cost‐effective method.

Objective Patients with rheumatoid arthritis (RA) and other systemic rheumatic diseases (SRDs) are at increased risk of developing herpes zoster (HZ). Zoster recombinant adjuvanted (ZRA) is a recombinant vaccine approved by the Food and Drug Administration in 2018. Concern has been raised that the ZRA may trigger disease flares in rheumatology patients who are immunocompromised. We investigated the impact of the ZRA vaccine in patients with RA and SRD and measured the incidence of flares and side effects. Methods A flare was defined as occurring within 12 weeks of vaccine administration by either 1) documentation of RA flare in office notes, telephone encounter, or patient portal communication or 2) new or increased dose of corticosteroids. Results We identified 403 patients (239 patients with RA and 164 patients with SRD) who received the ZRA vaccine from February 1, 2018, to February 1, 2019. We measured a 6.7% (n = 27) incidence of flare. Side effects occurred in 12.7% (n = 51) of patients. All flares and side effects were regarded as mild. Three cases of HZ were reported as occurring 2, 10, and 11 months after the vaccination. Conclusion In 403 patients who received the ZRA vaccine, the incidence of disease flares was 7% or less and that of side effects was 13% or less, both of which are less than the incidence rates observed in the pivotal trials.

The quest for a universal influenza vaccine holds great promise for mitigating the global burden of influenza-related morbidity and mortality. However, challenges persist in identifying conserved epitopes capable of eliciting robust and durable immune responses. In this study, we explore the influence of glycan evolution on H3 hemagglutinin from 1968 to present day and its impacts on protein structure, antigenicity and immunogenicity by using computational, biochemical and biophysical techniques. Structural characterization of HK/68 and Sing/16 by cryo-electron microscopy shows that while HK/68 is resistant to enzymatic deglycosylation, removal of glycans destabilizes the hyperglycosylated head and membrane-proximal region in Sing/16. Furthermore, the appearance of glycans in Sing/16 hemagglutinin head domain shifts the polyclonal immune response upon vaccination to target the esterase and stem. These insights expand our understanding of glycans beyond their role in protein folding and highlight the interplay among glycan integration and immune recognition to design a universal influenza vaccine. Structurally resolving glycans remains a challenge. Here, the authors analyse influenza H3 hemagglutinin glycan evolution to show that over five decades of glycan incorporation highly impact structural stability and epitope accessibility, particularly in the head domain, providing key insights for vaccine design.

Worldwide, freshwater vertebrate populations are declining with increasing pressure on rivers due to numerous environmental and climatic threats. Environmental DNA (eDNA) could potentially provide a more efficient and non‐invasive mechanism to monitor freshwater systems, either as a complement or in replacement to traditional methods to accurately assess species' distributions. Here, we utilize a hierarchical multispecies N‐mixture model to compare three fish sampling methods: traditional fyke netting and active and passive environmental DNA sampling along a 30 km stretch of the Canning River in Western Australia. We used the fitted model to compare capture probabilities among sampling methods and reveal the sampling effort required to describe the species assemblage. Results indicated that while all methods could detect fish, combined eDNA methodologies detected one more fish species than those caught by fyke netting. In addition, active eDNA sampling produced the highest capture probabilities and more consistently described the entire fish assemblage at any given site. Fyke netting and passive eDNA did not show significant differences in their average capture probabilities, and both methods had lower abilities to capture individual species than active eDNA. Active eDNA also required fewer replicate samples to detect the expected observed richness, and fyke netting required the most replicates. Additionally, a hierarchical multispecies abundance model showed that active environmental DNA (eDNA) sampling is the most effective method for monitoring freshwater fish populations. This study contributes to our understanding of eDNA in aquatic systems and demonstrates that, at least under current conditions, active sampling is still the preferred method in freshwater systems with low flow compared to both passive sampling and fyke netting. This study compared three fish sampling methods: traditional fyke netting, and active and passive environmental DNA sampling along a 30 km stretch of the Canning River in Western Australia. The effectiveness of the three different methods of detecting fish was tested with a hierarchical multispecies abundance model fit, with the model used to estimate both detection probability and replication effort required. This study contributes to our understanding of eDNA in aquatic systems and demonstrates that, at least under current conditions, active sampling is still the preferred method in freshwater systems with low flow compared to both passive sampling and fyke netting.

Purpose – The purpose of this paper is to identify aspects of leadership and evaluate their contribution to safeguarding vulnerable adults in healthcare organisations through conducting a critical review of literature. To identify or adapt a leadership framework to contribute to safeguarding vulnerable adults in healthcare organisations through analysis of the literature. Design/methodology/approach – The methodology was qualitative and inductive. It was based on constructivism and an interpretive theoretical perspective, beginning without hypothesis. Themes emerged during the process. A critical review of literature was undertaken to answer the research question. Literature was sourced from a variety of health and social care databases and grey literature. All inclusions underwent rigorous critical appraisal and a total of 18 papers were explored. Findings – The importance of clear leadership and direction was a common theme across the majority of sources. Aspects of leadership that can safeguard vulnerable adults in health care organisations include organisational culture, implementation of policies, procedures and frameworks, and reinforcing strong values and ethics around empowering individuals and delivering person-centred care. Through the meta-synthesis of findings, a model of leadership emerged. Research limitations/implications – The critical review utilised only one reviewer and the proposed leadership framework has not been empirically tested. Practical implications – The paper proposes a leadership framework that can be applied within healthcare organisations to safeguard vulnerable adults. Originality/value – This paper fulfils the need for evidence that supports the belief that strong leadership can safeguard vulnerable adults. It provides a comprehensive review of existing literature in this area.

ObjectiveThe risk of cardiovascular disease (CVD), including myocardial infarction (MI) and stroke, is increased in SLE patients and is underestimated by current prediction algorithms designed for the general population including the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score. The American College of Cardiology/American Heart Association now considers systemic inflammatory diseases such as SLE as risk enhancers for CVD. The purpose of this study was to develop an SLE-specific prediction tool to provide a more accurate estimate of CVD risk by including both traditional and SLE-related CVD risk factors.MethodsWe included SLE patients enrolled in the Brigham and Women’s Hospital SLE Cohort and collected one-year baseline data on traditional CVD risk factors, demographic and clinical features from the electronic medical record at cohort enrollment. Disease activity was rated using a modified physician global assessment (PGA) tool and SLE-related variables including autoantibodies, complement levels, and SLE manifestations were also collected. All subjects were required to have one or more visits for SLE during the baseline period. A up to ten-year follow-up period for CVD events began day +1 at end of baseline period (index date). The primary outcome was first major adverse cardiovascular events (MACE) defined as composite of first myocardial infarction (MI), stroke, or cardiac death, in the follow-up period. These were identified by ICD-9/10 codes and adjudicated by medical record review by board-certified cardiologists as either definite or probable events (not meeting all the criteria for MI or stroke definition). The secondary outcome was boarded to include first event of: carotid artery occlusion or stenosis, transient ischaemic attack, atrial fibrillation/flutter, heart failure, peripheral vascular disease, or angina pectoris. We excluded subjects with CVD events prior to the index date. Three Cox regression risk prediction models that categorized patients into low risk <7.5% risk, moderate risk 7.5-20%, and >20% risk over 10 years were derived: 1) primary outcome with definite/probable events, 2) combined model 1 and secondary outcomes, and 3) primary outcome with definite events only. We performed least absolute shrinkage and selection operator (LASSO) regression for variable selection and required one of the candidate predictors to be the 10-year ASCVD risk score. We assessed model performance using integrated time-dependent area under the curve, Harrell’s C statistic, optimism corrected C- statistic, integrated discrimination (IDI), and net reclassification index (NRI) using bootstrap resampling.ResultsWe included 1243 patients; 93.0% female and mean age of 41.6 (SD 13.3) years. There were 90 definite and probable MACEs (46 MIs, 36 strokes, and 19 cardiac deaths) and 211 secondary events over the follow-up period. The variables selected included: ASCVD risk score, disease activity (PGA at most recent baseline visit), disease duration, creatinine level, presence of anti-dsDNA, anti-RNP, lupus anticoagulant, anti-Ro60/SSA, and low C4 (table 1). Models 1 (primary outcomes with definite and probable events) and 3 (primary outcomes with definite events only) performed similarly and outperformed model 2 (combination of model 1 and secondary events) (table 2). Model performance improved in comparing risk predicted by ASCVD risk score alone vs. ASCVD risk score combined with selected SLE variables by LASSO regression for models 1 and 2, particularly at year 1. For these models, the number of SLE patients who were classified as high risk (>20%) more than doubled when selected SLE variables were added to the ASCVD model compared to the ASCVD model alone (table 3). The ten-year IDI and NRI were significant in the improvement direction.ConclusionOur novel SLE-specific cardiovascular risk prediction scores enhanced the performance of the traditional ASCVD risk algorithm and identified a greater number of SLE patients (at least two-fold) at high-risk for CVD events over 10 years. These models will need to be validated in a larger and more diverse population of SLE patients.Abstract 504 Table 1Beta Coefficients of ASCVD risk score and SLE Variables Selected by LASSO regression Variable Model 1 (Primary Outcome, Definite + Probable Events) Model 2 (Combined Model 1 and Secondary Events) Model 3 (Primary Outcome, Definite Events Only) Model with ASCVD risk score only ASCVD 6.42 5.09 6.51 Model with ASCVD risk score and SLE-Selected Variables ASCVD 5.44 4.58 5.40 Disease activity 0.31 0.33 0.34 Disease Duration 0.04 0.02 0.04 Creatinine Level 0.17 0.23 0.17 Anti-dsDNA Positive 0.35 0.03 0.33 Anti-RNP Positive 0.22 0.12 0.41 Lupus Anticoagulant 0.47 0.30 0.40 Anti-Ro60/SSA Positive 0.31 0.23 0.15 Low C4 0.49 0.40 0.51 Abbreviations: ASCVD, atherosclerotic cardiovascular diseaseAbstract 504 Table 2Performance of three cardiovascular risk prediction models Model Integrated Time- Dependent AUC Harrell’s C- statistic Optimism Optimism- Corrected Harrel’s C-statistic Year 1 AUC Year 10 AUC ASCVD only ASCVD and selected SLE variables ASCVD only ASCVD and selected SLE variables ASCVD only ASCVD and selected SLE variables 1 0.71 0.77 0.76 0.02 0.73 0.60 0.68 0.65 0.69 2 0.65 0.67 0.67 0.01 0.66 0.60 0.60 0.64 0.64 3 0.69 0.76 0.76 0.03 0.73 0.60 0.68 0.65 0.70 Abbreviations: ASCVD, atherosclerotic cardiovascular disease; AUC, area under the curveAbstract 504 Table 3Risk classification according to ASCVD risk score alone and ASCVD risk score + selected SLE variables* Model ASCVD Only n (%) ASCVD + Selected SLE Variables n (%) Low Risk (<7.5%) Moderate Risk (7.5%-20%) High Risk (>20%) Low Risk (<7.5%) Moderate Risk (7.5%-20%) High Risk (>20%) 1 746 (60.02) 480 (38.62) 17 (1.37) 885 (71.2) 316 (25.42) 42 (3.38) 2 281 (23.59) 281 (23.59) 629 (52.81) 290 (24.35) 549 (46.1) 352 (29.55) 3 1076 (86.56) 154 (12.39) 13 (1.05) 973 (78.28) 241 (19.39) 29 (2.33) Abbreviations: ASCVD, atherosclerotic cardiovascular disease* The SLE variables selected by LASSO included ASCVD model, disease activity (PGA at most recent visit), disease duration, creatinine level, presence of anti-dsDNA, anti-RNP, lupus anticoagulant, anti-Ro60/SSA, and low C4.

BackgroundMass cytometry (CyTOF) previously revealed that T follicular helper (Tfh) cells, T peripheral helper (Tph) cells, and age-associated B cells (ABCs) are robustly expanded in patients with newly diagnosed SLE. However, how these and other immune cell populations change over time in SLE remains unclear.MethodsWe employed CyTOF with two 39 marker panels (T and B cell) in cryopreserved PBMCs from 9 newly diagnosed SLE, 15 established SLE, and 14 non-inflammatory controls. FlowSOM and marker analysis by tSNE used to identify and quantify clusters based on their 39-parameter characterization. For the newly diagnosed cohort, PBMCs were analyzed at 3 time points (A=at diagnosis, B=6 months after the diagnosis, C=12 months after the diagnosis). Serum samples were also analyzed to quantify 65 cytokines by Luminex multiplex assay, and associations between cell types and cytokines assessed by Spearman correlation.ResultsWe first confirmed that among CD4 T cells, Tfh cells (PD-1hi CXCR5+ CD4 T cells) and Tph cells (PD-1hi CXCR5- CD4 T cells) were significantly increased in SLE patients. A broad analysis of B cells identified CD11c+ CD21- ABCs and CD19int Ki67hi B cell population significantly increased in the patients with SLE. This CD19int Ki67hi cluster was also CD21lo, CD11clow, CD27hi, and CD38hi, consistent with a Ki67hi plasmablast population (figure 1A). Among CD8 T cells, we identified one highly expanded cluster in SLE patients compared to controls, which expressed Ki67hi, ICOShi, PD-1int, CD57low, and granzyme Bint (figure 1A). In longitudinal analyses, the frequency of Tfh cells decreased over the first year of SLE, while Tph cells, ABCs, CD19int Ki67hi plasmablasts, and Ki67+ ICOS+ CD8 T cells remained elevated at 12 months (figure 1B). Correlation analyses including both immune cell frequencies and cytokines revealed an association of Tph cells, Ki67+ ICOS+ CD8 T cells, ABCs, and CD19int Ki67hi plasmablasts. These associated populations, but not Tfh cells, were also significantly correlated with CXCL13 and TSLP (figure 1C).Abstract 602 Figure 1Longitudinal CyTOF and cytokine analyses of newly diagnosed SLE. (A) Expanded two Ki67+ populations in PBMCs of SLE patients. (B) Longitudinal CyTOF analysis of PBMCs in SLE patients. (C) A hierarchical clustering heatmap with immune cell frequencies and cytokines in SLE.ConclusionsThis longitudinal immunophenotyping and cytokine profiling approach highlights persistent activation of a Tph-CXCL13-ABC-plasmablasts axis in both early and established phases of SLE.AcknowledgmentsWe thank the patients who donated samples and medical staffs at the Hospital.

Purpose – The purpose of this paper was to identify safeguarding concerns for vulnerable adults, including exploring the implementation of safeguarding policy and procedures into practice. This was achieved by reviewing the content of reflective assignments written by pre-registration student nurses, identifying areas of concerns and proposing action plans. Design/methodology/approach – A qualitative approach was initially utilised to scrutinise a random 10 per cent sample of work, which was thematically analysed. From this, an audit tool was devised and then applied to evaluate a 35 per cent sample of work from the following cohort of students. Approval and consent was gained. Findings – From the initial 10 per cent sample, themes emerged around: practice issues; areas for student's development and marking or assessment issues. The standardised audit tool was devised and applied to a 35 per cent random sample of work. This determined that students identified local safeguarding policies and procedures were being followed in the majority of placement areas, although application of the Mental Capacity Act remained inconsistent. Research limitations/implications – The assessor feedback from the reflective assignments was not available to the reviewers, limiting the reviewers ability to identify if assessors had recognised and corrected any policy or practice issues that the student raised. Only assignments from the adult field of nursing were considered within the scope of this study. The authors recommend further empirical investigation into this area. Practical implications – This paper offers knowledge that can be applied in practice within both academic and health care provider services that deliver and facilitate nursing education. It has generated an audit tool that can be utilised to evaluate the knowledge of pre-registration students and has resulted in the implementation of safeguarding adults policies within an academic institution. Originality/value – Safeguarding adults concerns may be identified through studying pre-registration student assignments and promptly acting upon any concerns raised. Aspects of good practice can be acknowledged within health care provider services.

The concept of adaptation is becoming part of mainstream public discourse on climate change. Yet the diversity, complexity, and novelty of the adaptation concept itself leads to interpretive flexibility, differing public understanding of (and engagement with) adaptation strategies, and hence differentiated policy responses. The boundary work of communicative practices and public understanding of the adaptation concept therefore requires empirical analysis in different cases and contexts. This study employs Q-methodology (a combined quantitative–qualitative social research method) to reveal the typologies of perspectives that emerge around the adaptation concept among a diverse group of citizen-stakeholders in the United Kingdom. Four such typologies are identified under the labels 1) top-down climate action, 2) collective action on climate change, 3) optimistic, values-focused adaptation, and 4) adaptation skepticism. The division between these perspectives reveals a perceived “responsibility gap” between the governmental–institutional and/or individual–community levels. Across the emergent discourses we find a consensual call for a multisector, multiscalar, and multistakeholder-led approach that posits adaptation as a contemporary, intragenerational problem, with a strong emphasis upon managing extreme weather events, and not as an abstract future problem. By attending to these public discourses in climate policy, this presents a potential means to lessen such a responsibility gap.