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Risk governance of nanomaterials and nanotechnologies has been traditionally mainly limited to risk assessment, risk management and life cycle assessment. Recent approaches have experimented with widening the scope and including economic, social, and ethical aspects. This paper reports on tests and stakeholder feedback on fine-tuning the use of ethical impact assessment guidelines (RiskGONE D3.6) and online tools adapting the CEN Workshop Agreement part 2 CWA 17145-2:2017 (E)) to support risk governance of nanomaterials, in the RiskGONE project. The EIA guidelines and tools are intended to be used as one module in a multicriteria decision support framework for risk governance of nanomaterials, but may also be used for a stand-alone ethical impact assessment.

Summary: Targeted inhibition of aberrant signaling is an important treatment strategy in cancer, but responses are often short-lived. Multi-drug combinations have the potential to mitigate this, but to avoid toxicity such combinations must be selective and given at low dosages. Here, we present a pipeline to identify promising multi-drug combinations. We perturbed an isogenic PI3K mutant and wild-type cell line pair with a limited set of drugs and recorded their signaling state and cell viability. We then reconstructed their signaling networks and mapped the signaling response to changes in cell viability. The resulting models, which allowed us to predict the effect of unseen combinations, indicated that no combination selectively reduces the viability of the PI3K mutant cells. However, we were able to validate 25 of the 30 combinations that we predicted to be anti-selective. Our pipeline enables efficient prioritization of multi-drug combinations from the enormous search space of possible combinations.

A drug used at the maximum tolerated dose can exert a strong selective pressure on cancer cells leading to resistance. In this study, the authors demonstrate the efficacy of using low dose of multiple drugs for preventing and treating resistance to EGFR tyrosine kinase inhibitors in NSCLC cells.

Decision-making balances the benefits of additional information with the cost of time, but it is unclear whether humans adjust this balance within individual decisions. Here, authors show that we do make such adjustments to suit contextual demands and suggest that these are driven by modulation of neural gain.

Nature Communications 7: Article number: 13526 (2016); Published: 24 November 2016; Updated: 18 January 2017 In Fig. 4c of this Article, the colour bars were inadvertently changed from graded to solid during the production process. The correct version of Fig. 4c appears below as Fig. 1.