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The frequency and intensity of extreme climatic events such as heatwaves are predicted to increase under continued climate change and rising atmospheric CO2. Degraded and fragmented ecosystems are at particular risk of being greatly impacted by such extreme events. The longleaf pine (LLP) savanna ecosystem, once the dominant ecosystem throughout the Southeast Coastal Plains of the United States, has been reduced to a small percentage of its pre‐colonization range. While the effect of heatwaves on grassland systems has been well explored, less focus has been given to the legacy effects of previous climatic events. Through a greenhouse experiment using Schizachyrium scoparium (little bluestem), a dominant understory grass species in LLP savanna ecosystems, we aimed to study the legacy effects of heatwaves (i.e., higher temperatures and lower precipitation and humidity) across multiple plant performance metrics and stress responses. S. scoparium had a negative response to an early heatwave, showing increased mortality, smaller maximum leaf length, fewer leaves, decreased specific leaf area (SLA), decreased leaf thickness, and reduced belowground net primary productivity (NPP) when compared to plants that did not experience a heatwave. S. scoparium individuals exposed to a late heatwave had fewer leaves, reduced SLA, and thinner leaves when compared to plants that did not experience a heatwave. While plants exposed to both an early and late heatwave experienced an increase in some stress responses as observed by increased catalase activity and plant mortality, they exhibited no change in other stress responses studied (e.g., maximum leaf length, relative growth rate, productivity, leaf thickness, peroxidase levels, or fuel load). Overall, our study revealed that S. scoparium may show neutral‐to‐positive legacy effects in response to multiple heatwaves. This indicates that LLP savanna ecosystems dominated by S. scoparium may display resistance to the predicted increased frequency of heatwaves in the southeastern United States, an important outcome for the heavily degraded and endangered ecosystem.

In our changing world, understanding plant community responses to global change drivers is critical for predicting future ecosystem composition and function. Plant functional traits promise to be a key predictive tool for many ecosystems, including grasslands; however, their use requires both complete plant community and functional trait data. Yet, representation of these data in global databases is sparse, particularly beyond a handful of most used traits and common species. Here we present the CoRRE Trait Data, spanning 17 traits (9 categorical, 8 continuous) anticipated to predict species’ responses to global change for 4,079 vascular plant species across 173 plant families present in 390 grassland experiments from around the world. The dataset contains complete categorical trait records for all 4,079 plant species obtained from a comprehensive literature search, as well as nearly complete coverage (99.97%) of imputed continuous trait values for a subset of 2,927 plant species. These data will shed light on mechanisms underlying population, community, and ecosystem responses to global change in grasslands worldwide.

Pancreatic ductal adenocarcinomas (PDAC) are among the most fatal cancers, in part due to frequent detection at advanced stages. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), the most sensitive diagnostic method of PDAC in current standard clinical practice, is invasive, costly, with access limited to major healthcare settings. Here, we present a non-invasive evaluation of plasma cell-free RNA (cfRNA) for PDAC detection in pre-diagnostic high-risk and de novo symptomatic patients presenting for EUS-FNA. We develop a cfRNA normalization method to account for preanalytical variation and handling effects and derive 29 potential cfRNA biomarkers for PDAC diagnosis using 153 samples collected prior to the EUS procedure. Biomarkers related to liver function are elevated in PDAC samples, including early-stage patients without liver metastasis. Classification of PDAC using these biomarkers is validated using an independent cohort of 95 samples. Our findings could help to improve diagnostic utility in high-risk and symptomatic individuals. Here, the authors developed a plasma cell-free RNA test for early PDAC detection in high-risk and symptomatic patients.

The vast developmental opportunities offered by the world’s coasts and oceans have attracted the attention of governments, private enterprises, philanthropic organizations, and international conservation organizations. High-profile dialogue and policy decisions on the future of the ocean are informed largely by economic and ecological research. Key insights from the social sciences raise concerns for food and nutrition security, livelihoods and social justice, but these have yet to gain traction with investors and the policy discourse on transforming ocean governance. The largest group of ocean-users – women and men who service, fish and trade from small-scale fisheries (SSF) – argue that they have been marginalized from the dialogue between international environmental and economic actors that is determining strategies for the future of the ocean. Blue Economy or Blue Growth initiatives see the ocean as the new economic frontier and imply an alignment with social objectives and SSF concerns. Deeper analysis reveals fundamental differences in ideologies, priorities and approaches. We argue that SSF are being subtly and overtly squeezed for geographic, political and economic space by larger scale economic and environmental conservation interests, jeopardizing the substantial benefits SSF provide through the livelihoods of millions of women and men, for the food security of around four billion consumers globally, and in the developing world, as a key source of micro-nutrients and protein for over a billion low-income consumers. Here, we bring insights from social science and SSF to explore how ocean governance might better account for social dimensions of fisheries.

Background Reliable evaluations of state-level policies are essential for identifying effective policies and informing policymakers’ decisions. State-level policy evaluations commonly use a difference-in-differences (DID) study design; yet within this framework, statistical model specification varies notably across studies. More guidance is needed about which set of statistical models perform best when estimating how state-level policies affect outcomes. Methods Motivated by applied state-level opioid policy evaluations, we implemented an extensive simulation study to compare the statistical performance of multiple variations of the two-way fixed effect models traditionally used for DID under a range of simulation conditions. We also explored the performance of autoregressive (AR) and GEE models. We simulated policy effects on annual state-level opioid mortality rates and assessed statistical performance using various metrics, including directional bias, magnitude bias, and root mean squared error. We also reported Type I error rates and the rate of correctly rejecting the null hypothesis (e.g., power), given the prevalence of frequentist null hypothesis significance testing in the applied literature. Results Most linear models resulted in minimal bias. However, non-linear models and population-weighted versions of classic linear two-way fixed effect and linear GEE models yielded considerable bias (60 to 160%). Further, root mean square error was minimized by linear AR models when we examined crude mortality rates and by negative binomial models when we examined raw death counts. In the context of frequentist hypothesis testing, many models yielded high Type I error rates and very low rates of correctly rejecting the null hypothesis (< 10%), raising concerns of spurious conclusions about policy effectiveness in the opioid literature. When considering performance across models, the linear AR models were optimal in terms of directional bias, root mean squared error, Type I error, and correct rejection rates. Conclusions The findings highlight notable limitations of commonly used statistical models for DID designs, which are widely used in opioid policy studies and in state policy evaluations more broadly. In contrast, the optimal model we identified--the AR model--is rarely used in state policy evaluation. We urge applied researchers to move beyond the classic DID paradigm and adopt use of AR models.

BackgroundWorldwide, emergency department (ED) attendances and admissions to acute care have increased significantly. Many EDs are adding physiotherapists to their team thereby allowing doctors to see more cases that are ‘urgent’. This is a move away from the ‘traditional’ physiotherapy service whereby the ED team refers patients to an outpatient physiotherapy service sometimes resulting in significant delays. Internationally, there is no agreed consensus on the role or value of ED-based physiotherapists.AimThe objective of this review was to retrieve, critically appraise and synthesise the evidence from studies relating to patients’ and healthcare professionals’ experiences and/or perceptions of physiotherapy services in the ED.MethodThis is a systematic review (SR) synthesising qualitative studies, which have considered patients’ (population 1) and healthcare professionals’ (population 2) experiences and/or perceptions (outcomes) of ED physiotherapy services (exposure). A comprehensive systematic search, limited to English language articles, was undertaken on seven electronic medical databases (Medline, EMBASE, CINAHL, AMED, BNI, PubMed and PEDro) for the period January 2006 to October 2016. Grey literature was identified using Google Scholar, reference lists and website searching. The Critical Appraisal Skills Programme (CASP) qualitative checklist was used to appraise all included studies. All studies were data extracted and quality appraised by two reviewers to enhance rigour and reduce bias.ResultsA total of 2163 studies were screened, 10 received full-text review and 7 studies were included in the final review. Six of the studies originated in Australia and one from the USA. The themes that emerged were as follows:Patients and healthcare professionals view ED-based physiotherapists as having (1) expert clinical skills and (2) an educational role.There is role confusion and lack of integration of the ED-based physiotherapist within the ED team.ConclusionThis review adds an in-depth human perspective to the current ED physiotherapy literature, which provides insight into how ED healthcare services and physiotherapy services specifically should be developed and delivered in the future. The knowledge from this review has implications for future education programmes, as well as development of both new care pathways and physiotherapy clinical roles.Research into ED-based physiotherapy services is predominantly quantitative. Despite the newness of the ED physiotherapy role, this review reveals that the provision of physiotherapists within EDs contributes value to both patients and staff. However, the dominance of Australian research means it is uncertain how it translates to the UK or elsewhere. There needs to be further UK-based research.

IntroductionVisual impairment is reported to affect 40%–50% of children with cerebral palsy (CP). Vision difficulties in the context of rehabilitation are often under-recognised, under-treated and therefore under-studied, pointing to an urgent need for the development of evidence-based vision interventions for infants and toddlers with cerebral vision impairment (CVI). We present the protocol of a multisite pragmatic pilot randomised controlled trial (RCT) of feasibility, acceptability and preliminary efficacy of an early vision-awareness and parent-directed environmental enrichment programme for infants with or at risk of CP under 7 months corrected age (CA) with vision impairment.The main objective is to determine the feasibility and acceptability of the Vision Intervention for Seeing Impaired Babies: Learning through Enrichment (VISIBLE) intervention. We will estimate the preliminary effects of the programme on infants’ visual functions and early development, as compared with standard community-based care (SCC).Methods and analysisA two-group RCT will be conducted. Infants at 3–6 months at entry, with severe visual impairment and at high risk of CP, will be enrolled and randomised (n=16 per group) to receive the VISIBLE intervention compared to SCC. Randomisation will be completed through an independent automated process (Research Electronic Data Capture). VISIBLE intervention will be delivered by a therapist through home visits (90–120 min) once every 2 weeks. Completion of 10 visits (80% of the intervention target dose) within 6 months is required for adherence to the VISIBLE trial. Outcome will be assessed at 12 months CA. Visual function will be evaluated with the Infant Battery for Vision, motor outcomes with the Peabody Developmental Motor Scales, Second Edition. Developmental quotients, infant quality of life, parent well-being and parent-infant relationship will be also monitored through standardised tools.Ethics and disseminationThe enrolling sites have historically demonstrated rapid and effective translation of successful evidence-based interventions into routine clinical practice, as well as the dissemination of the findings through local, national and international scientific meetings.Trial registration numberACTRN12618000932268.

Patients with metastatic pancreatic ductal adenocarcinoma survive longer if disease spreads to the lung but not the liver. Here we generated overlapping, multi-omic datasets to identify molecular and cellular features that distinguish patients whose disease develops liver metastasis (liver cohort) from those whose disease develops lung metastasis without liver metastases (lung cohort). Lung cohort patients survived longer than liver cohort patients, despite sharing the same tumor subtype. We developed a primary organotropism (pORG) gene set enriched in liver cohort versus lung cohort primary tumors. We identified ongoing replication stress response pathways in high pORG/liver cohort tumors, whereas low pORG/lung cohort tumors had greater densities of lymphocytes and shared T cell clonal responses. Our study demonstrates that liver-avid pancreatic ductal adenocarcinoma is associated with tolerance to ongoing replication stress, limited tumor immunity and less-favorable outcomes, whereas low replication stress, lung-avid/liver-averse tumors are associated with active tumor immunity that may account for favorable outcomes. Sears and colleagues found that ongoing replication stress pathways and T cell clonal responses differentiate liver and lung recurrence and are associated with different clinical outcomes in the context of pancreatic ductal adenocarcinoma.

IntroductionAccess to high-quality primary healthcare is limited for remote residents in Australia. Increasingly, remote health services are reliant on short-term or ‘fly-in, fly-out/drive-in, drive-out’ health workforce to deliver primary healthcare. A key strategy to achieving health service access equity, particularly evident in remote Australia, has been the development of Aboriginal Community Controlled Health Services (ACCHSs). This study aims to generate new knowledge about (1) the impact of short-term staffing in remote and rural ACCHSs on Aboriginal and Torres Strait Islander communities; (2) the potential mitigating effect of community control; and (3) effective, context-specific evidence-based retention strategies.Methods and analysisThis paper describes a 3-year, mixed methods study involving 12 ACCHSs across three states. The methods are situated within an evidence-based programme logic framework for rural and remote primary healthcare services. Quantitative data will be used to describe staffing stability and turnover, with multiple regression analyses to determine associations between independent variables (population size, geographical remoteness, resident staff turnover and socioeconomic status) and dependent variables related to patient care, service cost, quality and effectiveness. Qualitative assessment will include interviews and focus groups with clinical staff, clinic users, regionally-based retrieval staff and representatives of jurisdictional peak bodies for the ACCHS sector, to understand the impact of short-term staff on quality and continuity of patient care, as well as satisfaction and acceptability of services.Ethics and disseminationThe study has ethics approval from the Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research (project number DR03171), Central Australian Human Research Ethics Committee (CA-19-3493), Western Australian Aboriginal Health Ethics Committee (WAAHEC-938) and Far North Queensland Human Research Ethics Committee (HREC/2019/QCH/56393). Results will be disseminated through peer-reviewed journals, the project steering committee and community/stakeholder engagement activities to be determined by each ACCHS.