Current Directions in the Auricular

Electrical stimulation of the auricular vagus nerve (aVNS) is an emerging electroceutical technology in the field of bioelectronic medicine with applications in therapy. Artificial modulation of the afferent vagus nerve – a powerful entrance to the brain – affects a large number of physiological processes implicating interactions between the brain and body. Engineering aspects of aVNS determine its efficiency in application. The relevant safety and regulatory issues need to be appropriately addressed. In particular, in silico modeling acts as a tool for aVNS optimization. The evolution of personalized electroceuticals using novel architectures of the closed-loop aVNS paradigms with biofeedback can be expected to optimally meet therapy needs. For the first time, two international workshops on aVNS have been held in Warsaw and Vienna in 2017 within the scope of EU COST Action “European network for innovative uses of EMFs in biomedical applications (BM1309).” Both workshops focused critically on the driving physiological mechanisms of aVNS, its experimental and clinical studies in animals and humans, in silico aVNS studies, technological advancements, and regulatory barriers. The results of the workshops are covered in two reviews, covering physiological and engineering aspects. The present review summarizes on engineering aspects – a discussion of physiological aspects is provided by our accompanying article (Kaniusas et al., 2019). Both reviews build a reasonable bridge from the rationale of aVNS as a therapeutic tool to current research lines, all of them being highly relevant for the promising aVNS technology to reach the patient.European Cooperation in Science and TechnologyThe Austrian Research Promotion Agenc

Microbiota-dependent activation of the myeloid calcineurin-NFAT pathway inhibits B7H3- and B7H4-dependent anti-tumor immunity in colorectal cancer

Bacterial sensing by intestinal tumor cells contributes to tumor growth through cell-intrinsic activation of the calcineurin-NFAT axis, but the role of this pathway in other intestinal cells remains unclear Here, we found that myeloid-specific deletion of calcineurin in mice activated protective CD8(+) T cell responses and inhibited colorectal cancer (CRC) growth. Microbial sensing by myeloid cells promoted calcineurin- and NFAT-dependent interleukin 6 (IL-6) release, expression of the co-inhibitory molecules B7H3 and B7H4 by tumor cells, and inhibition of CD8(+) T cell-dependent anti-tumor immunity. Accordingly, targeting members of this pathway activated protective CD8(+) T cell responses and inhibited primary and metastatic CRC growth. B7H3 and B7H4 were expressed by the majority of human primary CRCs and metastases, which was associated with low numbers of tumor-infiltrating CD8(+) T cells and poor survival. Therefore, a microbiota-, calcineurin-, and B7H3/B7H4-dependent pathway controls anti-tumor immunity, revealing additional targets for immune checkpoint inhibition in microsatellite-stable CRC

STRENGTHENING THE EUROPEAN RARE EARTHS SUPPLY-CHAIN Challenges and policy options A REPORT BY THE EUROPEAN RARE EARTHS COMPETENCY NETWORK (ERECON)

ERECON (2014) Strengthening the European rare earths supply chain: Challengesand policy options. Kooroshy, J., G. Tiess, A. Tukker, and A. Walton (eds.).Policy recommendations:1.Maintaining and strengthening the European Rare Earth Elements (REE) skills and knowledge base through research funding, science and technology education and international cooperation.Without cutting-edge research and technical expertise, a European high-tech REE industry cannot flourish. The EC and Member States should support funding for research grants, scholarships, and training networks, and enhance European and international cooperation through coordinated calls, researcher exchanges, and joint high-level conferences.2.Creating the basis for informed decision-making on REEs through a European Critical Materials Observatory.Mapping and monitoring of REE supply chains is necessary for informed decision-making. Expertise in Europe could be pooled in a virtual Critical Materials Observatory that provides the public with consistent and authoritative knowledge on REEs (e.g., information on advanced exploration projects, prices, key demand and supply trends, and the urban mine potential).3.Support promising technologies through funding industry-led pilot plants for innovative HREE processing.The EC, industry and Member States should accelerate the commercialization and scaling up of key technologies through co-financing industry-led pilot plants. This should include pilots for REE recovery from heavy rare earths-rich minerals, direct-alloy recycling routes, process and sensor equipment for REE recycling, and REE recovery from industrial residues.4.Levelling the playing field for European HREE exploration through co-funding for prefeasibility and bankable feasibility studies.Support from federal and state governments in the U.S., Australia and Canada has played a critical role in advancing project exploration. The EC and Member States should evaluate possibilities for supporting the extensive R&D necessary for pre-feasibility and bankable feasibility studies, to avoid high quality deposits in Europe simply going unexplored.5.Making waste management REE-friendly through eco-design, incentive schemes for collecting priority waste products, and streamlining policy and waste regulation.The EC and Member States should promote recycling-friendly design to help identify and recover REE components in waste more easily. Potential incentives for stimulating REE waste collection should be evaluated and the shipment of REE wastes should be facilitated. More consistency should also be created in implementing and applying existing waste regulations.6.Boost supply security and de-risk strategic REE investment cases through enhanced cooperation among European end-users and other stakeholders.Leading end-users should engage in strategic cooperation across industry and with governments. This could include setting up a voluntary European ‘critical raw materials fund’, establishing a ‘European Resource Alliance’ similar to the German Rohstoffallianz, and convening a high-level taskforce to examine ways in which public funding could support resilient REE supply chains for Europe