IRGC Guidelines for the Governance of Systemic Risks

IRGC’s guidelines for the governance of systemic risks addresses the question of how to deal with systemic risks in the context of system transitions, i.e., in situations that require adaptation to new context conditions or transformation of an organisation or ecosystem. The guidelines comprise seven interlinked steps. The guidelines successful implementation depends on strong leadership and the willingness to adapt or revise processes, focus on mid- and long-term issues, and accept and resolve trade-offs

Workshop Report: The Economics of Precision Medicine

This report from a multi-stakeholder workshop on the ‘Economics of precision medicine’ addresses the issues of cost-effectiveness, as well as the need to revise how economic and social value can be valorised and financed, and to develop new business models for fundamentally personalised gene therapies with high up-front costs

Demand-Side Flexibility for Energy Transitions: Policy Recommendations for Developing Demand Response

As a follow-up to IRGC's report on demand-side flexibility for energy transitions, this Policy Brief highlights that increasing flexibility in power systems is needed to accommodate higher shares of non-controllable and intermittent renewable generation, and that this requires changes to the market design and regulatory framework, to facilitate the development and deployment of appropriate technologies and market-based instruments (e.g. taxes and subsidies). The Policy Brief focuses on demand response (DR), since it is emerging as a powerful demand-side energy management option to deliver flexibility. Specifically, DR can contribute to reducing overall electricity consumption or shifting demand in such a way that consumption better follows generation, particularly intermittent wind and solar

Demand-Side Flexibility for Energy Transitions: Ensuring the Competitive Development of Demand Response Options

This report provides an overview of the current debates about demand response development, focusing primarily on Europe, with some comparisons to the United States. ‘Demand response’ includes strategies that involve end-use customers adapting or altering their electricity demand in response to grid conditions or market prices. It is viewed as a multi-purpose power-system resource that enhances the energy system’s capacity to cope with increasing demand, rising costs of conventional transmission and distribution grids, and increasing share of intermittent renewable energy. The report reviews risks, opportunities, potential, consumer engagement market design, and policy and regulation

Systems-Based Analysis of the \u3cem\u3eSarcocystis neurona\u3c/em\u3e Genome Identifies Pathways That Contribute to a Heteroxenous Life Cycle

Sarcocystis neurona is a member of the coccidia, a clade of single-celled parasites of medical and veterinary importance including Eimeria, Sarcocystis, Neospora, and Toxoplasma. Unlike Eimeria, a single-host enteric pathogen, Sarcocystis, Neospora, and Toxoplasma are two-host parasites that infect and produce infectious tissue cysts in a wide range of intermediate hosts. As a genus, Sarcocystis is one of the most successful protozoan parasites; all vertebrates, including birds, reptiles, fish, and mammals are hosts to at least one Sarcocystis species. Here we sequenced Sarcocystis neurona, the causal agent of fatal equine protozoal myeloencephalitis. The S. neurona genome is 127 Mbp, more than twice the size of other sequenced coccidian genomes. Comparative analyses identified conservation of the invasion machinery among the coccidia. However, many dense-granule and rhoptry kinase genes, responsible for altering host effector pathways in Toxoplasma and Neospora, are absent from S. neurona. Further, S. neurona has a divergent repertoire of SRS proteins, previously implicated in tissue cyst formation in Toxoplasma. Systems-based analyses identified a series of metabolic innovations, including the ability to exploit alternative sources of energy. Finally, we present an S. neurona model detailing conserved molecular innovations that promote the transition from a purely enteric lifestyle (Eimeria) to a heteroxenous parasite capable of infecting a wide range of intermediate hosts. IMPORTANCE Sarcocystis neurona is a member of the coccidia, a clade of single-celled apicomplexan parasites responsible for major economic and health care burdens worldwide. A cousin of Plasmodium, Cryptosporidium, Theileria, and Eimeria, Sarcocystis is one of the most successful parasite genera; it is capable of infecting all vertebrates (fish, reptiles, birds, and mammals—including humans). The past decade has witnessed an increasing number of human outbreaks of clinical significance associated with acute sarcocystosis. Among Sarcocystis species, S. neurona has a wide host range and causes fatal encephalitis in horses, marine mammals, and several other mammals. To provide insights into the transition from a purely enteric parasite (e.g., Eimeria) to one that forms tissue cysts (Toxoplasma), we present the first genome sequence of S. neurona. Comparisons with other coccidian genomes highlight the molecular innovations that drive its distinct life cycle strategies

The genome of Onchocerca volvulus, agent of river blindness

Human onchocerciasis is a serious neglected tropical disease caused by the filarial nematode Onchocerca volvulus that can lead to blindness and chronic disability. Control of the disease relies largely on mass administration of a single drug, and the development of new drugs and vaccines depends on a better knowledge of parasite biology. Here, we describe the chromosomes of O. volvulus and its Wolbachia endosymbiont. We provide the highest-quality sequence assembly for any parasitic nematode to date, giving a glimpse into the evolution of filarial parasite chromosomes and proteomes. This resource was used to investigate gene families with key functions that could be potentially exploited as targets for future drugs. Using metabolic reconstruction of the nematode and its endosymbiont, we identified enzymes that are likely to be essential for O. volvulus viability. In addition, we have generated a list of proteins that could be targeted by Federal-Drug-Agency-approved but repurposed drugs, providing starting points for anti-onchocerciasis drug development