Endothelin-3 like immunoreactivity in plasma of patients with cirrhosis of the liver

A highly specific and sensitive radioimmunoassay (RIA) has been established for determination of endothelin-3 like immunoreactivity in human plasma to investigate its possible role in hemodynamic alterations due to liver disease. Crossreactivity with other endothelin isoforms was always below 4 %, the lower detection limit following extraction on Sep-Pak C18 cartridges was 0.5 pg/ml. The concentration of endothelin-3 (mean ± SEM) was 4.16 ± 0.56 pg/ml (n = 13) in plasma of patients with cirrhosis of the liver, three fold higher than in age matched controls (1.35 ± 0.27 pg/ml, n = 12, p < 0.01). Plasma immunoreactivity was confirmed to be endothelin-3 related by reverse-phase HPLC. These data could suggest a role of plasma endothelin-3 in circulatory changes, as they occur in cirrhosis of the liver

Transferring climate change knowledge

Accurate climate projections are required for climate adaptation and mitigation. Earth system model simulations, used to project climate change, inherently make approximations in their representation of small-scale physical processes, such as clouds, that are at the root of the uncertainties in global mean temperature's response to increased greenhouse gas concentrations. Several approaches have been developed to use historical observations to constrain future projections and reduce uncertainties in climate projections and climate feedbacks. Yet those methods cannot capture the non-linear complexity inherent in the climate system. Using a Transfer Learning approach, we show that Machine Learning, in particular Deep Neural Networks, can be used to optimally leverage and merge the knowledge gained from Earth system model simulations and historical observations to more accurately project global surface temperature fields in the 21st century. For the Shared Socioeconomic Pathways (SSPs) 2-4.5, 3-7.0 and 5-8.5, we refine regional estimates and the global projection of the average global temperature in 2081-2098 (with respect to the period 1850-1900) to 2.73{\deg}C (2.44-3.11{\deg}C), 3.92{\deg}C (3.5-4.47{\deg}C) and 4.53{\deg}C (3.69-5.5{\deg}C), respectively, compared to the unconstrained 2.7{\deg}C (1.65-3.8{\deg}C), 3.71{\deg}C (2.56-4.97{\deg}C) and 4.47{\deg}C (2.95-6.02{\deg}C). Our findings show that the 1.5{\deg}C threshold of the Paris' agreement will be crossed in 2031 (2028-2034) for SSP2-4.5, in 2029 (2027-2031) for SSP3-7.0 and in 2028 (2025-2031) for SSP5-8.5. Similarly, the 2{\deg}C threshold will be exceeded in 2051 (2045-2059), 2044 (2040-2047) and 2042 (2038-2047) respectively. Our new method provides more accurate climate projections urgently required for climate adaptation

Predicting In Vivo Anti-Hepatofibrotic Drug Efficacy Based on In Vitro High-Content Analysis

Background/Aims Many anti-fibrotic drugs with high in vitro efficacies fail to produce significant effects in vivo. The aim of this work is to use a statistical approach to design a numerical predictor that correlates better with in vivo outcomes. Methods High-content analysis (HCA) was performed with 49 drugs on hepatic stellate cells (HSCs) LX-2 stained with 10 fibrotic markers. ~0.3 billion feature values from all cells in >150,000 images were quantified to reflect the drug effects. A systematic literature search on the in vivo effects of all 49 drugs on hepatofibrotic rats yields 28 papers with histological scores. The in vivo and in vitro datasets were used to compute a single efficacy predictor (Epredict). Results We used in vivo data from one context (CCl4 rats with drug treatments) to optimize the computation of Epredict. This optimized relationship was independently validated using in vivo data from two different contexts (treatment of DMN rats and prevention of CCl4 induction). A linear in vitro-in vivo correlation was consistently observed in all the three contexts. We used Epredict values to cluster drugs according to efficacy; and found that high-efficacy drugs tended to target proliferation, apoptosis and contractility of HSCs. Conclusions The Epredict statistic, based on a prioritized combination of in vitro features, provides a better correlation between in vitro and in vivo drug response than any of the traditional in vitro markers considered.Institute of Bioengineering and Nanotechnology (Singapore)Singapore. Biomedical Research CouncilSingapore. Agency for Science, Technology and ResearchSingapore-MIT Alliance for Research and Technology Center (C-185-000-033-531)Janssen Cilag (R-185-000-182-592)Singapore-MIT Alliance Computational and Systems Biology Flagship Project (C-382-641-001-091)Mechanobiology Institute, Singapore (R-714-001-003-271

La mutation du juge des libertés et de la détention

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Lire, voir, entendre - Grégoire Korganow - Prisons 67065

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Justice en situation - Le juge des libertés et de la détention entre présent et avenir

International audienc

Apport de la musicothérapie dans la prise en charge de l'anxiété

Music therapy, historical and descriptive. Music therapy, which can be active or receptive, is a therapeutic modality that fits into the field of art therapy according to the teaching of AFRATAPEM. Anxiety, a cardinal symptom in medicine. Anxiety is a symptom very often encountered as much in psychiatry as in somatic medicine. The development of non-drug treatments can bring a real benefit in terms of public health. State of scientific research in 2018. Research on this topic is still in its infancy, with many pilot studies or small samples studies. In psychiatry, it seems necessary to offer at least 10 biweekly sessions of active music therapy to achieve efficacy on anxiety. In somatic medicine, there is a particular interest in receptive music therapy used in peri-interventional, with encouraging results. Conclusion: in 2018, the presumption of effectiveness of music-dominant art therapy for the management of anxiety, both in psychiatric and somatic medicine, seems consistent. The bulk of the research work remains to be done, with large-scale studies whose results will allow conclusions to be drawn with a high level of scientific proof, and perhaps to introduce this therapeutic modality into daily clinical practice.La musicothérapie, historique et descriptif. La musicothérapie, qui peut être active ou réceptive, est une modalité thérapeutique qui s’inscrit dans le champ de l’art-thérapie selon l’enseignement de l’AFRATAPEM. L’anxiété, un symptôme cardinal en médecine. L’anxiété est un symptôme très fréquemment rencontré, autant en psychiatrie qu’en médecine somatique. Le développement de traitements non médicamenteux pourra apporter un réel bénéfice en termes de santé publique. État de la recherche scientifique en 2018. La recherche sur ce sujet en est encore à ses débuts, avec beaucoup d’études pilotes ou basées sur de petits échantillons. En psychiatrie, il semble nécessaire de proposer au moins 10 séances bihebdomadaires de musicothérapie active pour obtenir une efficacité sur l’anxiété. En médecine somatique, on note un intérêt particulier pour la musicothérapie réceptive utilisée en péri-interventionnel, avec des résultats encourageants. Conclusion : en 2018, la présomption d'efficacité de l’art-thérapie à dominante musicale pour la prise en charge de l'anxiété, tant en milieu psychiatrique qu'en médecine somatique, semble consistante. L'essentiel du travail de recherche reste maintenant à accomplir, avec des études de grande envergure dont les résultats permettront de tirer des conclusions avec un haut niveau de preuve scientifique, et peut-être d’introduire cette modalité thérapeutique en pratique clinique quotidienne