Responses to environmental and societal challenges for our unstable earth (RESCUE) foresight initiative

Humankind is currently facing unprecedented changes in the Earth system, that have arisen at a rapidly growing rate because of human activities: among others, unsustainable exploitation and consumption of natural resources and accelerating perturbations of the environment. The systemic understanding of global environmental change has expanded markedly, but societal and policy- relevant drivers and consequences are still to be fully explored. In particular, the complex Earth system requires interdisciplinary studies at scales compatible to political and societal agendas, and some stronger common, integrated foundations between natural, social and human sciences to be established. In this context, the “Responses to Environmental and Societal Challenges for our Unstable Earth” (RESCUE, www.esf.org) foresight initiative will help the European science community and the related science policy actors address the societal and scientific challenges related to global environmental change, including its human dimensions, and help stimulate an integrated response from natural, social and human sciences. This will be achieved through the following key objectives: * To propose a strategic process for natural, social and human sciences to improve their interdisciplinary synergy, to respond efficiently to societal and policy-relevant needs; * To articulate new scientific issues related to global change, especially those of transdisciplinary nature or of major society-driven relevance; * To explore new approaches towards interdisciplinary science, and to facilitate the ‘revolution’ in education and capacity building it requires. Through its analyses and recommendations, RESCUE will help enable the scientific community, together with other actors and key stakeholders, to develop medium to long-term strategies for future research activities and applications. It is anticipated that RESCUE will impact society by favouring common strategic understanding and coordination, and transformative education delivery, to help ensure global sustainable governance. The presentation will give insights about the latest progress of the RESCUE foresight initiative run under the auspices of ESF (www.esf.org) and COST (www.cost.esf.org)

IMBER – Research for marine sustainability: Synthesis and the way forward

The Integrated Marine Biogeochemistry and Ecosystem Research (IMBER) project aims at developing a comprehensive understanding of and accurate predictive capacity of ocean responses to accelerating global change and the consequent effects on the Earth system and human society. Understanding the changing ecology and biogeochemistry of marine ecosystems and their sensitivity and resilience to multiple drivers, pressures and stressors is critical to developing responses that will help reduce the vulnerability of marine-dependent human communities. This overview of the IMBER project provides a synthesis of project achievements and highlights the value of collaborative, interdisciplinary, integrated research approaches as developed and implemented through IMBER regional programs, working groups, project-wide activities, national contributions, and external partnerships. A perspective is provided on the way forward for the next 10 years of the IMBER project as the global environmental change research landscape evolves and as new areas of marine research emerge. IMBER science aims to foster collaborative, interdisciplinary and integrated research that addresses key ocean and social science issues and provides the understanding needed to propose innovative societal responses to changing marine systems

IMBER- Research for Marine Sustainability: Synthesis and the Way Forward

The Integrated Marine Biogeochemistry and Ecosystem Research (IMBER) project aims at developing a comprehensive understanding of and accurate predictive capacity of ocean responses to accelerating global change and the consequent effects on the Earth system and human society. Understanding the changing ecology and biogeochemistry of marine ecosystems and their sensitivity and resilience to multiple drivers, pressures and stressors is critical to developing responses that will help reduce the vulnerability of marine-dependent human communities. This overview of the IMBER project provides a synthesis of project achievements and highlights the value of collaborative, interdisciplinary, integrated research approaches as developed and implemented through IMBER regional programs, working groups, project-wide activities, national contributions, and external partnerships. A perspective is provided on the way forward for the next 10 years of the IMBER project as the global environmental change research landscape evolves and as new areas of marine research emerge. IMBER science aims to foster collaborative, interdisciplinary and integrated research that addresses key ocean and social science issues and provides the understanding needed to propose innovative societal responses to changing marine systems

Tumor-Infiltrating CD3- NK Cells Are More Effective than CD3+ T Cells in Killing Autologous Melanoma Cells

We have studied the phenotype and functional activity of tumor-infiltrating lymphocytes (TIL) derived from eight human melanomas cultured for up to 60 d in the presence of recombinant IL-2. In the early period of the cultures, TIL were predominantly T cells of CD8+ phenotype and contained 10–30% of CD3- cells. Four of the five early TIL cultures tested in a cytotoxicity assay displayed a degree of MHC-unrestricted lysis on a series of autologous and allogenic melanoma cell lines as well as the K562 natural killer-sensitive target. With longer periods of time in culture, all TIL lines showed a decrease in lytic activity that was associated with the loss of CD3- cells. Thus, most of the killing of short-term TIL cultures appeared to be mediated by CD3- natural killer cells, whereas CD3+ T cells were found to be weak anti-tumor effectors. Even though the CD3+ T cells were not cytotoxic on K562 targets, their lytic activity (even weak) against melanoma cells appeared to be non-MHC restricted and was blocked by anti-CD3 antibodies. In addition, cytotoxicity of the CD3+ TIL cultures was compared to that of a CD3-/NKH1+ cell line purified from peripheral blood. It was found that natural killer cells were much more potent than CD3+ TIL on the melanoma cell lines tested

IMBeR into the future Science Plan and Implementation Strategy 2016-2025

The Integrated Marine Biosphere Research (IMBeR) project, formerly the Integrated Marine Biogeochemistry and Ecosystem Research (IMBER1) project, is a global environmental change research initiative. Since its start in 2005, IMBeR has advanced understanding about potential marine environmental effects of global change, and the impacts and linkages to human systems at multiple scales. It is apparent that complex environmental issues and associated societal/sustainability choices operate at and across the interfaces of natural and social sciences and the humanities, and require both basic, curiosity-driven research and problem-driven, policy-relevant research. Collaborative, disciplinary, interdisciplinary, transdisciplinary and integrated research that addresses key ocean science issues generated by and/or impacting society is required to provide evidence-based knowledge and guidance, along with options for policy-makers, managers and marine-related communities, to help achieve sustainability of the marine realm under global change. This recognition underlies a new vision, “Ocean sustainability under global change for the benefit of society”, to guide IMBeR research for the next decade (2016-2025). This vision recognises that the evolution of marine ecosystems (including biogeochemical cycles and human systems) is linked to natural and anthropogenic drivers and stressors, as articulated in the new IMBeR research goal to, “Understand, quantify and compare historic and present structure and functioning of linked ocean and human systems to predict and project changes including developing scenarios and options for securing or transitioning towards ocean sustainability”. To implement its new vision and goal in the next decade, IMBeR’s mission is to, “Promote integrated marine research and enable capabilities for developing and implementing ocean sustainability options within and across the natural and social sciences, and communicate relevant information and knowledge needed by society to secure sustainable, productive and healthy oceans”. This Science Plan and Implementation Strategy provides a 10-year (2016-2025) marine research agenda for IMBeR. It is developed around three Grand Challenges (GC, see Graphical Executive Summary) focusing on climate variability, global change and drivers and stressors. The qualitative and quantitative understanding of historic and present ocean variability and change (Grand Challenge I) are the basis for scenarios, projections and predictions of the future (Grand Challenge II). These are linked in Grand Challenge III to understand how humans are causing the variability and changes, and how they, in turn, are impacted by these changes, including feedbacks between the human and ocean systems. Priority research areas with overarching and specific research questions are identified for each Grand Challenge. The Grand Challenges are supplemented with Innovation Challenges (IC, see graphical executive summary) that focus on new topics for IMBeR where research is needed and where it is believed that major achievements can be made within three to five years. The Innovation Challenges also provide a means for IMBeR to adjust its focus as major science discoveries are made and new priorities arise, especially regarding scientific innovations

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Artificial intelligence extension of the OSCAR-IB criteria

Artificial intelligence (AI)-based diagnostic algorithms have achieved ambitious aims through automated image pattern recognition. For neurological disorders, this includes neurodegeneration and inflammation. Scalable imaging technology for big data in neurology is optical coherence tomography (OCT). We highlight that OCT changes observed in the retina, as a window to the brain, are small, requiring rigorous quality control pipelines. There are existing tools for this purpose. Firstly, there are human-led validated consensus quality control criteria (OSCAR-IB) for OCT. Secondly, these criteria are embedded into OCT reporting guidelines (APOSTEL). The use of the described annotation of failed OCT scans advances machine learning. This is illustrated through the present review of the advantages and disadvantages of AI-based applications to OCT data. The neurological conditions reviewed here for the use of big data include Alzheimer disease, stroke, multiple sclerosis (MS), Parkinson disease, and epilepsy. It is noted that while big data is relevant for AI, ownership is complex. For this reason, we also reached out to involve representatives from patient organizations and the public domain in addition to clinical and research centers. The evidence reviewed can be grouped in a five-point expansion of the OSCAR-IB criteria to embrace AI (OSCAR-AI). The review concludes by specific recommendations on how this can be achieved practically and in compliance with existing guidelines

DOC dynamics in the northwestern Mediterranean Sea (DYFAMED site)

International audienceDissolved organic carbon (DOC) distribution and dynamics are investigated at the DYFAMED site (central Ligurian Sea, NW Mediterranean) in relation to hydrological and biological contexts, using a 4-year time-series dataset (1991-1994). The DYFAMED site is regarded as a one-dimensional station where simple hydrological mechanisms prevail and where the ecosystem is quite well understood. An average vertical profile of DOC concentration ([DOC]) indicates that maximal concentrations and variability are concentrated in the surface layers. For depths >800 m, the annual variations are on average similar to the analytical standard deviation (∼2 μM). The "composite" [DOC] distribution (average distribution over a typical year, integrating about 40 monthly profiles) for surface waters (0-200 m) is closely related to hydrological and phytoplanktonic forcings. It exhibits summer DOC accumulation in surface waters, due to spring-summer stratification and successive phytoplanktonic events such as spring and summer blooms, and winter DOC removal to deeper waters, due to intense vertical mixing. The analysis of vertical [DOC] gradient at 100-m depth as a function of the integrated DOC content in the 0-100-m layer makes it possible to objectively distinguish three specific periods: the winter vertical mixing period, the period of stratification and spring phytoplankton bloom, and the period of stratification re-inforcement and summer-fall phytoplankton bloom. We recalculate the vertical DOC fluxes to deep waters using a larger original dataset, after the first direct calculation (Deep-Sea Res. 40 (10) (1993) 1963, 1972) that was reproduced for other oceanic areas. The seasonal variations of the "composite" [DOC] distribution in surface waters are significantly correlated to the apparent oxygen utilization distribution, but the biogeochemical significance of such a correlation is still under examination. The global significance of our local findings is presented and the role of the oceanic DOC in the global carbon cycle is emphasized, especially with respect to several current issues, such as the oceanic "missing sink" and the equivalence between new production and exported production