A Pronounced Inflammatory Activity Characterizes the Early Fracture Healing Phase in Immunologically Restricted Patients

Immunologically restricted patients such as those with autoimmune diseases or malignancies often suffer from delayed or insufficient fracture healing. In human fracture hematomas and the surrounding bone marrow obtained from immunologically restricted patients, we analyzed the initial inflammatory phase on cellular and humoral level via flow cytometry and multiplex suspension array. Compared with controls, we demonstrated higher numbers of immune cells like monocytes/macrophages, natural killer T (NKT) cells, and activated T helper cells within the fracture hematomas and/or the surrounding bone marrow. Also, several pro-inflammatory cytokines such as Interleukin (IL)-6 and Tumor necrosis factor α (TNFα), chemokines (e.g., Eotaxin and RANTES), pro-angiogenic factors (e.g., IL-8 and Macrophage migration inhibitory factor: MIF), and regulatory cytokines (e.g., IL-10) were found at higher levels within the fracture hematomas and/or the surrounding bone marrow of immunologically restricted patients when compared to controls. We conclude here that the inflammatory activity on cellular and humoral levels at fracture sites of immunologically restricted patients considerably exceeds that of control patients. The initial inflammatory phase profoundly differs between these patient groups and is probably one of the reasons for prolonged or insufficient fracture healing often occurring within immunologically restricted patients. View Full-Tex

From Planetary Boundaries to national fair shares of the global safe operating space — How can the scales be bridged?

The planetary boundaries framework proposes quantitative global limits to the anthropogenic perturbation of crucial Earth system processes, and thus marks out a planetary safe operating space for human activities. Yet, decisions regarding resource use and emissions are mostly made at less aggregated scales, by national and sub-national governments, businesses, and other local actors. To operationalize the planetary boundaries concept, the boundaries need to be translated into and aligned with targets that are relevant at these decision-making scales. In this paper, we develop a framework that addresses the biophysical, socio-economic, and ethical dimensions of bridging across scales, to provide a consistently applicable approach for translating the planetary boundaries into national-level fair shares of Earth’s safe operating space. We discuss our findings in the context of previous studies and their implications for future analyses and policymaking. In this way, we link the planetary boundaries framework to widely-applied operational and policy concepts for more robust strong sustainability decision-making

CTLA-4 mediates inhibitory function of mesenchymal stem/stromal cells

Mesenchymal stem/stromal cells (MSCs) are stem cells of the connective tissue, possess a plastic phenotype, and are able to differentiate into various tissues. Besides their role in tissue regeneration, MSCs perform additional functions as a modulator or inhibitor of immune responses. Due to their pleiotropic function, MSCs have also gained therapeutic importance for the treatment of autoimmune diseases and for improving fracture healing and cartilage regeneration. However, the therapeutic/immunomodulatory mode of action of MSCs is largely unknown. Here, we describe that MSCs express the inhibitory receptor CTLA-4 (cytotoxic T lymphocyte antigen 4). We show that depending on the environmental conditions, MSCs express different isoforms of CTLA-4 with the secreted isoform (sCTLA-4) being the most abundant under hypoxic conditions. Furthermore, we demonstrate that the immunosuppressive function of MSCs is mediated mainly by the secretion of CTLA-4. These findings open new ways for treatment when tissue regeneration/fracture healing is difficult

Water Use in Global Livestock Production—Opportunities and Constraints for Increasing Water Productivity

Increasing population, change in consumption habits, and climate change will likely increase the competition for freshwater resources in the future. Exploring ways to improve water productivity especially in food and livestock systems is important for tackling the future water challenge. Here we combine detailed data on feed use and livestock production with Food and Agriculture Organization of the United Nations (FAO) statistics and process-based crop-water model simulations to comprehensively assess water use and water productivity in the global livestock sector. We estimate that, annually, 4,387 km3 of blue and green water is used for the production of livestock feed, equaling about 41% of total agricultural water use. Livestock water productivity (LWP; protein produced per m3 of water) differs by several orders of magnitude between livestock types, regions, and production systems, indicating a large potential for improvements. For pigs and broilers, we identify large opportunities to increase LWP by increasing both feed water productivity (FWP; feed produced per m3 of water) and feed use efficiency (FUE; protein produced per kg of feed) through better crop and livestock management. Even larger opportunities to increase FUE exist for ruminants, while the overall potential to increase their FWP is low. Substantial improvements of FUE can be achieved for ruminants by supplementation with feed crops, but the lower FWP of these feed crops compared to grazed biomass limits possible overall improvements of LWP. Therefore, LWP of ruminants, unlike for pigs and poultry, does not always benefit from a trend toward intensification, as this is often accompanied by increasing crop supplementation

A Nexus Approach for the MENA Region—From Concept to Knowledge to Action

There is wide agreement that a nexus or integrated approach to managing and governing natural resources such as land, water, and energy can improve environmental, climate, human, and political security. However, few if any countries in the MENA region have made progress in implementing such an approach. There appear to be several constraints inhibiting the development and adoption of nexus approaches. These constraints include strong sectoral silos, insufficient incentives for integrated planning and policy making at all levels, and limited vision, knowledge, and practical experience to guide successful implementation. In turn, the limited implementation and hence lack of empirical evidence of a nexus approach, which could demonstrate its benefits, does little to strengthen political will for the development of adequate incentives, structures, and procedures. Against this backdrop, this paper presents five case studies which take an integrated approach, in three MENA countries, namely Jordan, Lebanon, and Morocco. Based on an analytical framework developed here, the paper analyses and compares the success factors for nexus implementation, and also for transfer and upscaling. The analysis emphasizes the need for appropriate framework conditions, targeted investments and pioneering actors, to make integrated approaches across sectors and levels work. With the evidence presented, the paper aims to set in motion a positive or virtuous cycle of generating more nexus evidence, improved framework conditions, further nexus implementation on the ground, and from that even more nexus evidence. Finally, the paper contributes to overcoming the repeated requests for better definition and conceptualization of the nexus, which often has slowed down adoption of the concept

Volkswirtschaftliche Bedeutung Olympische Winterspiele Graubünden 2022

Der Verein Graubünden 2022 beabsichtigte, sich als offizielle Kandidatur der Schweiz für die Olympischen Winterspiele 2022 zu bewerben. Im Hinblick auf die politische Diskussion und das Kandidaturdossier zur Bewerbung wurde das Forschungsnetzwerk Rütter Soceco, Eidgenössische Hochschule für Sport Magglingen EHSM und Institut für Tourismuswirtschaft ITW Hochschule Luzern beauftragt, die potenziellen wirtschaftlichen Wirkungen der Olympischen Winterspiele auf die Austragungsregion und die gesamte Schweiz zu analysieren. Die Studie gliedert sich in zwei Hauptteile und eine Zusammenfassung der Erkenntnisse. Der erste Teil des Berichts, der am 30. Oktober 2012 publiziert wurde, fokussiert auf den wirtschaftlichen Primärimpuls (Budgets und touristische Ausgaben) und die damit verbundenen volkswirtschaftlichen Wirkungen von Graubünden 2022. Er weist die direkten und indirekten Wertschöpfungs- und Beschäftigungswirkungen sowie die Steuerwirkungen im Kanton Graubünden und in der übrigen Schweiz aus, unter besonderer Berücksichtigung der Wirkungen auf den Tourismus. Für den Gesamtbericht wurden die Wirkungen für die drei Regionen Davos/Kloster, Oberengadin und „“übrige Region““ regionalisiert. Der zweite Teil der Studie zeigt die potenziellen langfristigen Wirkungen (Legacy) von Graubünden 2022 qualitativ auf. Dabei werden acht Themen unterschieden und die wichtigsten mit der Durchführung verbundenen Risiken dargestellt. Wie die Potenziale ausgeschöpft werden, wird wesentlich davon abhängen, dass die Legacyaspekte frühzeitig in die Planung der OWS Graubünden 22 einbezogen werden

Integrative medicine during the intensive phase of chemotherapy in pediatric oncology in Germany: a randomized controlled trial with 5-year follow up

Background: Integrative medicine is used frequently alongside chemotherapy treatment in pediatric oncology, but little is known about the influence on toxicity. This German, multi-center, open-label, randomized controlled trial assessed the effects of complementary treatments on toxicity related to intensive-phase chemotherapy treatment in children aged 1-18 with the primary outcome of the toxicity sum score. Secondary outcomes were chemotherapy-related toxicity, overall and event-free survival after 5 years in study patients. Methods: Intervention and control were given standard chemotherapy according to malignancy & tumor type. The intervention arm was provided with anthroposophic supportive treatment (AST); given as anthroposophic base medication (AMP), as a base medication for all patients and additional on-demand treatment tailored to the intervention malignancy groups. The control was given no AMP. The toxicity sum score (TSS) was assessed using NCI-CTC scales. Results: Data of 288 patients could be analyzed. Analysis did not reveal any statistically significant differences between the AST and the control group for the primary endpoint or the toxicity measures (secondary endpoints). Furthermore, groups did not differ significantly in the five-year overall and event-free survival follow up. Discussion: In this trial findings showed that AST was able to be safely administered in a clinical setting, although no beneficial effects of AST between group toxicity scores, overall or event-free survival were shown

Our future in the Anthropocene biosphere

The COVID-19 pandemic has exposed an interconnected and tightly coupled globalized world in rapid change. This article sets the scientific stage for understanding and responding to such change for global sustainability and resilient societies. We provide a systemic overview of the current situation where people and nature are dynamically intertwined and embedded in the biosphere, placing shocks and extreme events as part of this dynamic; humanity has become the major force in shaping the future of the Earth system as a whole; and the scale and pace of the human dimension have caused climate change, rapid loss of biodiversity, growing inequalities, and loss of resilience to deal with uncertainty and surprise. Taken together, human actions are challenging the biosphere foundation for a prosperous development of civilizations. The Anthropocene reality—of rising system-wide turbulence—calls for transformative change towards sustainable futures. Emerging technologies, social innovations, broader shifts in cultural repertoires, as well as a diverse portfolio of active stewardship of human actions in support of a resilient biosphere are highlighted as essential parts of such transformations. © 2021, The Author(s)