Dynameta: a dynamic platform for ecological meta-analyses in R Shiny

Meta-analyses have brought a significant improvement in our understanding of global biodiversity change. However, in ecology the static nature of current approaches, both in terms of the data included and the predictions presented, make meta-analyses difficult for policymakers to fully interrogate and adopt. Here we introduce Dynameta, a living-review (i.e. continually updateable) R Shiny platform for interactive ecological meta-analyses, oriented around testing the effect of anthropogenic threats on biodiversity. This platform is written as an R package and can be applied in the context of any meta-analytic PICO (Population, Intervention, Comparator, and Outcome) question concerning the effect of any threat on any taxonomic group, for any biodiversity metric and with relevance to all geographic regions. Our hope is that, alongside other existing tools, Dynameta can help encourage the broader adoption of dynamic meta-analyses in ecology

A mixed-methods feasibility study of a new digital health support package for people after stroke : The Recovery-focused Community support to Avoid readmissions and improve Participation after Stroke (ReCAPS) intervention

Background Evidence for digital health programmes to support people living with stroke is growing. We assessed the feasibility of a protocol and procedures for the Recovery-focused Community support to Avoid readmissions and improve Participation after Stroke (ReCAPS) trial. Methods We conducted a mixed-method feasibility study. Participants with acute stroke were recruited from three hospitals (Melbourne, Australia). Eligibility: Adults with stroke discharged from hospital to home within 10 days, modified Rankin Score 0–4 and prior use of Short Message System (SMS)/email. While in hospital, recruited participants contributed to structured person-centred goal setting and completed baseline surveys including self-management skills and health-related quality of life. Participants were randomised 7–14 days after discharge via REDCap® (1:1 allocation). Following randomisation, the intervention group received a 12-week programme of personalised electronic support messages (average 66 messages sent by SMS or email) aligned with their goals. The control group received six electronic administrative messages. Feasibility outcomes included the following: number of patients screened and recruited, study retainment, completion of outcome measures and acceptability of the ReCAPS intervention and trial procedures (e.g. participant satisfaction survey, clinician interviews). Protocol fidelity outcomes included number of goals developed (and quality), electronic messages delivered, stop messages received and engagement with messages. We undertook inductive thematic analysis of interview/open-text survey data and descriptive analysis of closed survey questions. Results Between November 2018 and October 2019, 312 patients were screened; 37/105 (35%) eligible patients provided consent (mean age 61 years; 32% female); 33 were randomised (17 to intervention). Overall, 29 (88%) participants completed the12-week outcome assessments with 12 (41%) completed assessments in the allocated timeframe and 16 also completing the satisfaction survey (intervention=10). Overall, trial participants felt that the study was worthwhile and most would recommend it to others. Six clinicians participated in one of three focus group interviews; while they reported that the trial and the process of goal setting were acceptable, they raised concerns regarding the additional time required to personalise goals. Conclusion The study protocol and procedures were feasible with acceptable retention of participants. Consent and goal personalisation procedures should be centralised for the phase III trial to reduce the burden on hospital clinicians. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12618001468213 (date 31/08/2018); Universal Trial Number: U1111-1206-723

Real communities of virtual plants explain biodiversity on just three assumptions

To illuminate mechanisms supporting diversity in plant communities, we construct 2D cellular automata and 'grow' virtual plants in real experiments. The plants are 19 different, fully validated functional types drawn from universal adaptive strategy theory. The scale of approach is far beyond that of even the most ambitious investigations in the physical world. By simulating 496 billion plant-environment interactions, we succeed in creating conditions that sustain high diversity realistically and indefinitely. Our simulations manipulate the levels of, and degree of heterogeneity in the supply of, resources, external disturbances and invading propagules. We fail to reproduce this outcome when we adopt the assumptions of unified neutral theory. The 19 functional types in our experiments respond in complete accordance with universal adaptive strategy theory. We find that spatial heterogeneity is a strong contributor to long-term diversity, but temporal heterogeneity is less so. The strongest support of all comes when an incursion of propagules is simulated. We enter caveats and suggest further directions for working with cellular automata in plant science. We conclude that although (i) the differentiation of plant life into distinct functional types, (ii) the presence of environmental heterogeneity and (iii) the opportunity for invasion by propagules can all individually promote plant biodiversity, all three appear to be necessary simultaneously for its long-term maintenance. Though further, and possibly more complex, sets of processes could additionally be involved, we consider it unlikely that any set of conditions more minimal than those described here would be sufficient to deliver the same outcome

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Global Governance or Global Government? An Examination of Anarchy vs. Hierarchy, Global Civil Society and International Governmental Organizations

The goal of this paper is to argue that we currently have a system of global government rather than global governance. To prove this, It examines two main areas, international hierarchy and global society. In terms of hierarchy, it considers the existence of hierarchy among nations as well as a practical hierarchy in global decision making and functioning. This is shown via an examination of American Empire, Power Transition Theory, the Washington Consensus, the United Nations and the North Atlantic Treaty Organization. The second major focus, global society, considers how nations utilize international organizations and technology to allow for the free exchange of ideas, culture, trade and currency. This is shown via an examination of Bretton Woods, International Monetary Fund, World Bank, General Agreement on Tariffs and Trade, international infrastructure, and the United Nations. This paper contends that since both an international hierarchy and a global society exist, the term global government most accurately describes the current world order

Development of Novel Murine BRAF^V600E-Driven Papillary Thyroid Cancer Cell Lines for Modeling of Disease Progression and Preclinical Evaluation of Therapeutics

The Cancer Genome Atlas study in thyroid cancer exposed the genomic landscape of ~500 PTCs and revealed BRAFV600E-mutant tumors as having different prognosis, contrasting indolent cases and those with more invasive disease. Here, we describe the generation and characterization of six novel BRAFV600E-driven papillary thyroid cancer (PTC) cell lines established from a BrafV600E+/−/Pten+/−/TPO-Cre mouse model that spontaneously develop thyroid tumors. The novel cell lines were obtained from animals representing a range of developmental stages and both sexes, with the goal of establishing a heterogeneous panel of PTC cell lines sharing a common driver mutation. These cell lines recapitulate the genetics and diverse histopathological features of BRAFV600E-driven PTC, exhibiting differing degrees of growth, differentiation, and invasive potential that may help define mechanisms of pathogenesis underlying the heterogeneity present in the patient population. We demonstrate that these cell lines can be used for a variety of in vitro applications and can maintain the potential for in vivo transplantation into immunocompetent hosts. We believe that these novel cell lines will provide powerful tools for investigating the molecular basis of thyroid cancer progression and will lead to the development of more personalized diagnostic and treatment strategies for BRAFV600E-driven PTC

Development of Novel Murine BRAFV600E-Driven Papillary Thyroid Cancer Cell Lines for Modeling of Disease Progression and Preclinical Evaluation of Therapeutics

The Cancer Genome Atlas study in thyroid cancer exposed the genomic landscape of ~500 PTCs and revealed BRAFV600E-mutant tumors as having different prognosis, contrasting indolent cases and those with more invasive disease. Here, we describe the generation and characterization of six novel BRAFV600E-driven papillary thyroid cancer (PTC) cell lines established from a BrafV600E+/−/Pten+/−/TPO-Cre mouse model that spontaneously develop thyroid tumors. The novel cell lines were obtained from animals representing a range of developmental stages and both sexes, with the goal of establishing a heterogeneous panel of PTC cell lines sharing a common driver mutation. These cell lines recapitulate the genetics and diverse histopathological features of BRAFV600E-driven PTC, exhibiting differing degrees of growth, differentiation, and invasive potential that may help define mechanisms of pathogenesis underlying the heterogeneity present in the patient population. We demonstrate that these cell lines can be used for a variety of in vitro applications and can maintain the potential for in vivo transplantation into immunocompetent hosts. We believe that these novel cell lines will provide powerful tools for investigating the molecular basis of thyroid cancer progression and will lead to the development of more personalized diagnostic and treatment strategies for BRAFV600E-driven PTC