Clean and efficient energies for Europe : socio-economic impact of energy research

Report of the independent expert panelLaunched in 1994, the Fourth Framework Programme (FP4) covering research and demonstration aimed to improve the security of energy supply and to reduce the impact of the production and use of energy on the environment, in particular CO2 and the other greenhouse gases. Other important EU objectives were also addressed including strengthening the technological basis of the energy industry (e.g. employment and export potential), improving European social and economic cohesion and contributing to co-operation with third countries. It also supported research on overall energy RTD strategy in the inter-disciplinary area of energy-environment-economy. Six years after the Programme’s launch, at a stage when most of the projects have been completed, and the Sixth Framework Programme is being planned, it was considered appropriate to assess not only the scientific and technical quality of the completed projects, but also their impact on society, the economy and the environment. The present analysis was organised to allow quick feedback for the preparation of the new Framework Programme. This was achieved by convening a panel of ten experts from different Member States. Using questionnaires, project final reports and direct contacts where necessary, the Panel investigated the expected overall impact by examining the scientific and technical results as well as the social and economic impact of a sample of about 90 already finished Non-Nuclear Energy projects, most of them three years ago (time necessary to expect some concrete results), representing in total a e84 million investment by the Commission. The contribution to Community policies, particularly emphasised in the present Framework Programme, as well as the Programmes’s addition to European Added Value were both explored. The results of this impact assessment of about one-fifth of the projects funded under the Non-Nuclear Energy Programme of the Fourth Framework Programme for the period 1994-1998 (better known as JOULE), were analysed and critically reviewed and are presented in this report. Among the main conclusions of the report, it is worth noting that the vast majority of the examined projects have developed new technical advances. Furthermore, the commercial leverage of funded research projects is positive and its major non-commercial impact is on the improvement of the environment and particularly on CO2 emissions. The social and economic impact remains, in general, limited, but could be improved through better understanding and application of the European Added Value principles. The Fifth Framework Programme made a further step towards refocusing European energy research and aiming to provide effective responses to the major challenges facing European society. It is important to fully exploit the experience and the results from the research undertaken under the FP4 since the knowledge generated relates directly to the objectives of the next Energy Research Programme. It also provides the groundwork for launching effective and innovative approaches to implementing the “European Research Area”. Based on the present pilot exercise, the remaining projects of the Non-Nuclear Energy Programme of the FP4 will be assessed to provide a full picture of the impact of the Programme. Finally, the present pilot exercise should help to provide a methodological base for other research programmes to develop quick-response, feedback to decision-makers to allow for the development of better informed research policies and actions. It should also help to bring more quickly the results and socio-economic implications of European research to European citizens, companies and institutions

Burden of disease from inadequate water, sanitation and hygiene for selected adverse health outcomes: An updated analysis with a focus on low- and middle-income countries

Background To develop updated estimates in response to new exposure and exposure-response data of the burden of diarrhoea, respiratory infections, malnutrition, schistosomiasis, malaria, soil-transmitted helminth infections and trachoma from exposure to inadequate drinking-water, sanitation and hygiene behaviours (WASH) with a focus on low- and middle-income countries. Methods For each of the analysed diseases, exposure levels with both sufficient global exposure data for 2016 and a matching exposure-response relationship were combined into population-attributable fractions. Attributable deaths and disability-adjusted life years (DALYs) were estimated for each disease and, for most of the diseases, by country, age and sex group separately for inadequate water, sanitation and hygiene behaviours and for the cluster of risk factors. Uncertainty estimates were computed on the basis of uncertainty surrounding exposure estimates and relative risks. Findings An estimated 829,000 WASH-attributable deaths and 49.8 million DALYs occurred from diarrhoeal diseases in 2016, equivalent to 60% of all diarrhoeal deaths. In children under 5 years, 297,000 WASH-attributable diarrhoea deaths occurred, representing 5.3% of all deaths in this age group. If the global disease burden from different diseases and several counterfactual exposure distributions was combined it would amount to 1.6 million deaths, representing 2.8% of all deaths, and 104.6 million DALYs in 2016. Conclusions Despite recent declines in attributable mortality, inadequate WASH remains an important determinant of global disease burden, especially among young children. These estimates contribute to global monitoring such as for the Sustainable Development Goal indicator on mortality from inadequate WASH

The Targeting of Plasmalemmal Ceramide to Mitochondria during Apoptosis

Ceramide is a key lipid mediator of cellular processes such as differentiation, proliferation, growth arrest and apoptosis. During apoptosis, ceramide is produced within the plasma membrane. Although recent data suggest that the generation of intracellular ceramide increases mitochondrial permeability, the source of mitochondrial ceramide remains unknown. Here, we determine whether a stress-mediated plasmalemmal pool of ceramide might become available to the mitochondria of apoptotic cells. We have previously established annexin A1—a member of a family of Ca2+ and membrane-binding proteins—to be a marker of ceramide platforms. Using fluorescently tagged annexin A1, we show that, upon its generation within the plasma membrane, ceramide self-associates into platforms that subsequently invaginate and fuse with mitochondria. An accumulation of ceramide within the mitochondria of apoptotic cells was also confirmed using a ceramide-specific antibody. Electron microscopic tomography confirmed that upon the formation of ceramide platforms, the invaginated regions of the plasma membrane extend deep into the cytoplasm forming direct physical contacts with mitochondrial outer membranes. Ceramide might thus be directly transferred from the plasma membrane to the mitochondrial outer membrane. It is conceivable that this “kiss-of-death” increases the permeability of the mitochondrial outer membrane thereby triggering apoptosis

The implications of three major new trials for the effect of water, sanitation and hygiene on childhood diarrhea and stunting: a consensus statement

BACKGROUND: Three large new trials of unprecedented scale and cost, which included novel factorial designs, have found no effect of basic water, sanitation and hygiene (WASH) interventions on childhood stunting, and only mixed effects on childhood diarrhea. Arriving at the inception of the United Nations' Sustainable Development Goals, and the bold new target of safely managed water, sanitation and hygiene for all by 2030, these results warrant the attention of researchers, policy-makers and practitioners. MAIN BODY: Here we report the conclusions of an expert meeting convened by the World Health Organization and the Bill and Melinda Gates Foundation to discuss these findings, and present five key consensus messages as a basis for wider discussion and debate in the WASH and nutrition sectors. We judge these trials to have high internal validity, constituting good evidence that these specific interventions had no effect on childhood linear growth, and mixed effects on childhood diarrhea. These results suggest that, in settings such as these, more comprehensive or ambitious WASH interventions may be needed to achieve a major impact on child health. CONCLUSION: These results are important because such basic interventions are often deployed in low-income rural settings with the expectation of improving child health, although this is rarely the sole justification. Our view is that these three new trials do not show that WASH in general cannot influence child linear growth, but they do demonstrate that these specific interventions had no influence in settings where stunting remains an important public health challenge. We support a call for transformative WASH, in so much as it encapsulates the guiding principle that - in any context - a comprehensive package of WASH interventions is needed that is tailored to address the local exposure landscape and enteric disease burden

Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization

Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.Peer reviewe