CoreSOAR Core Degradation State-of-the Art Report Update: Conclusions [in press]

In 1991 the CSNI published the first State-of-the-Art Report on In-Vessel Core Degradation, which was updated to 1995 under the EC 3rd Framework programme. These covered phenomena, experimental programmes, material data, main modelling codes, code assessments, identification of modelling needs, and conclusions including the needs for further research. This knowledge was fundamental to such safety issues as in-vessel melt retention of the core, recovery of the core by water reflood, hydrogen generation and fission product release. In the last 20 years, there has been much progress in understanding, with major experimental series finished, e.g. the integral in-reactor Phébus FP tests, while others have many tests completed, e.g. the electrically-heated QUENCH series on reflooding degraded rod bundles, and one test using a debris bed. The small-scale PRELUDE/PEARL experiments study debris bed quench, while LIVE examines melt pool behaviour in the lower head using simulant materials. The integral severe accident modelling codes, such as MELCOR and MAAP (USA) and ASTEC (Europe), encapsulate current knowledge in a quantitative way. After two EC-funded projects on the SARNET network of excellence, continued in NUGENIA, it is timely to take stock of the vast range of knowledge and technical improvements gained in the experimental and modelling areas. The CoreSOAR project, in NUGENIA/SARNET, drew together the experience of 11 European partners to update the state of the art in core degradation, finishing at the end of 2018. The review covered knowledge of phenomena, available integral experiments, separate-effects data, modelling codes and code validation, then drawing overall conclusions and identifying needs for further research. The final report serves as a reference for current and future research programmes concerning core degradation in NUGENIA, in other EC research projects such as in Horizon2020 and for projects under the auspices of OECD/NEA/CSNI

Widespread white matter microstructural abnormalities in bipolar disorder: Evidence from mega- and meta-analyses across 3,033 individuals

Fronto-limbic white matter (WM) abnormalities are assumed to lie at the heart of the pathophysiology of bipolar disorder (BD); however, diffusion tensor imaging (DTI) studies have reported heterogeneous results and it is not clear how the clinical heterogeneity is related to the observed differences. This study aimed to identify WM abnormalities that differentiate patients with BD from healthy controls (HC) in the largest DTI dataset of patients with BD to date, collected via the ENIGMA network. We gathered individual tensor-derived regional metrics from 26 cohorts leading to a sample size of N = 3033 (1482 BD and 1551 HC). Mean fractional anisotropy (FA) from 43 regions of interest (ROI) and average whole-brain FA were entered into univariate mega- and meta-analyses to differentiate patients with BD from HC. Mega-analysis revealed significantly lower FA in patients with BD compared with HC in 29 regions, with the highest effect sizes observed within the corpus callosum (R2 = 0.041, Pcorr < 0.001) and cingulum (right: R2 = 0.041, left: R2 = 0.040, Pcorr < 0.001). Lithium medication, later onset and short disease duration were related to higher FA along multiple ROIs. Results of the meta-analysis showed similar effects. We demonstrated widespread WM abnormalities in BD and highlighted that altered WM connectivity within the corpus callosum and the cingulum are strongly associated with BD. These brain abnormalities could represent a biomarker for use in the diagnosis of BD. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org

Widespread white matter microstructural abnormalities in bipolar disorder: evidence from mega- and meta-analyses across 3033 individuals

Fronto-limbic white matter (WM) abnormalities are assumed to lie at the heart of the pathophysiology of bipolar disorder (BD); however, diffusion tensor imaging (DTI) studies have reported heterogeneous results and it is not clear how the clinical heterogeneity is related to the observed differences. This study aimed to identify WM abnormalities that differentiate patients with BD from healthy controls (HC) in the largest DTI dataset of patients with BD to date, collected via the ENIGMA network. We gathered individual tensor-derived regional metrics from 26 cohorts leading to a sample size of N = 3033 (1482 BD and 1551 HC). Mean fractional anisotropy (FA) from 43 regions of interest (ROI) and average whole-brain FA were entered into univariate mega- and meta-analyses to differentiate patients with BD from HC. Mega-analysis revealed significantly lower FA in patients with BD compared with HC in 29 regions, with the highest effect sizes observed within the corpus callosum (R2 = 0.041, Pcorr < 0.001) and cingulum (right: R2 = 0.041, left: R2 = 0.040, Pcorr < 0.001). Lithium medication, later onset and short disease duration were related to higher FA along multiple ROIs. Results of the meta-analysis showed similar effects. We demonstrated widespread WM abnormalities in BD and highlighted that altered WM connectivity within the corpus callosum and the cingulum are strongly associated with BD. These brain abnormalities could represent a biomarker for use in the diagnosis of BD. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org

Pioglitazone could induce remission in major depression: a meta-analysis

Romain Colle,1,* Delphine de Larminat,1,* Samuel Rotenberg,1 Franz Hozer,1 Patrick Hardy,1 C&eacute;line Verstuyft,2 Bruno F&egrave;ve,3,* Emmanuelle Corruble1,* 1Psychiatry Department, H&ocirc;pital Bic&ecirc;tre, INSERM, UMR S1178, University Paris-Sud, Assistance Publique-H&ocirc;pitaux de Paris, Le Kremlin Bic&ecirc;tre, France; 2Molecular Genetic, Pharmacogenetics and Hormonology Department, H&ocirc;pital Bic&ecirc;tre, INSERM UMR_S1184, Centre IMVA, University Paris-Sud, Assistance Publique-H&ocirc;pitaux de Paris, Le Kremlin Bic&ecirc;tre, France; 3Endocrinology Department, INSERM UMR_S938, H&ocirc;pital Saint-Antoine, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire ICAN, Sorbonne Universit&eacute;s, Universit&eacute; Pierre et Marie Curie, Assistance Publique des H&ocirc;pitaux de Paris, Paris, France *These authors contributed equally to this work Background: Pioglitazone, a selective agonist of the nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-&gamma;), prescribed for the treatment of type 2 diabetes, could have antidepressant properties. However, its potential to induce remission of major depressive episodes, the optimal clinical target for an antidepressant drug, is a matter of concern. Indeed, only one out of four double-blind randomized controlled trials show higher remission rates with pioglitazone than with control treatments. Hence, the main aim of this study was to perform a meta-analysis of the efficacy of pioglitazone for the treatment of MDE, focusing on remission rates.Methods: Four double-blind randomized controlled trials, comprising 161 patients with an MDE, were included in this meta-analysis. Pioglitazone was studied either alone (one study) or as add-on therapy to conventional treatments (antidepressant drugs or lithium salts). It was compared either to placebo (three studies) or to metformin (one study). Remission was defined by a Hamilton Depression Rating Scale score &lt;8 after treatment.Results: Pioglitazone could induce higher remission rates than control treatments (27% versus 10%, I2=17.3%, fixed-effect model: odds ratio [OR]&nbsp;=3.3, 95% confidence interval [95% CI; 1.4; 7.8], P=0.008). The OR was even higher in the subgroup of patients with major depressive disorder (n=80; 23% versus 8%, I2=0.0%; fixed-effect model: OR&nbsp;=5.9, 95% CI [1.6; 22.4], P=0.009) and in the subgroup of patients without metabolic comorbidities (n=84; 33% versus 10%, I2=0.0%; fixed-effect model: OR&nbsp;=5.1, 95% CI [1.5; 17.9], P=0.01). As compared to control treatments, results suggest six patients would need to be treated with pioglitazone in order to achieve the possibility of one more remission.Conclusion: Pioglitazone, either alone or as add-on therapy to conventional treatments, could induce remission of MDE, suggesting that drugs with PPAR-&gamma; agonist properties may be true and clinically relevant antidepressants, even in patients without metabolic comorbidities. Keywords: pioglitazone, major depressive episode, major depressive disorder, bipolar disorder, remission, meta-analysi

Generalizability of pharmacologic and psychotherapy trial results for late-life unipolar depression.

Despite evidence of low representativeness of clinical trial results for depression in adults, the generalizability of clinical trial results for late-life depression is unknown. This study sought to quantify the representativeness of pharmacologic and psychotherapy clinical trial results for late-life unipolar depression. Data were derived from the 2004-2005 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a nationally representative sample of 34,653 adults from the United States population. To assess the generalizability of clinical trial results for late-life depression, we applied a standard set of eligibility criteria representative of pharmacologic and psychotherapy clinical trials to all individuals aged 65 years and older in NESARC with a DSM-IV diagnosis of MDE and no lifetime history of mania/hypomania (n = 273) and in a subsample of individuals seeking help for depression (n = 78). More than four of ten respondents and about two of ten respondents would have been excluded by at least one exclusion criterion in a typical pharmacologic and psychotherapy efficacy trial, respectively. Similar results (i.e.41.1% and 25.9%, respectively) were found in the subsample of individuals seeking help for depression. Excess percentage of exclusion in typical pharmacologic studies was accounted for by the criterion "significant medical condition". We also found that populations typically included in pharmacologic and psychotherapy clinical trials for late-life unipolar depression may substantially differ. Psychotherapy trial results may be representative of most patients with late-life unipolar depression in routine clinical practice. By contrast, pharmacologic clinical trials may not be readily generalizable to community samples

The SAFEST project towards pan-European Lab on Corium Behavior in Severe Accidents. Main Objectives and RetD priorities.

International audienceNo individual country has sufficient resources to address all severe accident important phenomena within the framework of a national research programme, therefore optimised use of resources and the collaboration at European and international level are very important. Integrating European severe accident research facilities into a pan-European laboratory for severe accident and corium studies and providing resources to other European partners for better understanding of possible accident scenarios and phenomena is necessary in order to improve safety of existing and, in the long-term, of future reactors.SAFEST (Severe Accident Facilities for European Safety Targets) is a European project networking the European corium experimental laboratories with the objective to establish coordination activities, enabling the development of a common vision and of research roadmaps for the next years, and of the management structure to achieve these goals. One of the main objectives is to address and resolve the variety of the remaining severe accident issues related to accident analysis and corium behaviour. The project is a valuable asset for the fulfilment of the severe accident RetD programmes that are being set up after the Fukushima Daiichi accidents and the subsequent European stress tests, addressing both national and European objectives.Roadmaps on European severe accident experimental research for water reactors and for GenIV technologies will be drafted. Joint RetD is conducted to improve the excellence of the SAFEST facilities this includes measurement of corium physical properties, improvement of instrumentation, consensus on scaling law rationales and cross comparison of material analyses.Joint experimental research is a clear objective in the SAFEST project to provide solutions for stabilisation of severe accident and termination of consequences for the current Gen II and III plants. Consequently, the knowledge obtained in SAFEST shall lead to improved severe accident management measures, which are essential for reactor safety. In addition, it will offer competitive advantages for the nuclear industry and contribute to the long-term sustainability of nuclear energy

European Nuclear Thermodynamic Database Validated and Applicable in Severe Accident Codes: ENTHALPY Project

International audienc