Débat sur les perspectives économiques à court terme du 10 octobre 2002

Les prévisions occupent une place particulière dans le débat public en économie. Elles sont généralement considérées comme des prédictions, qualifiées fréquemment d’optimistes ou de pessimistes, comme si elles dépendaient de l’humeur des équipes qui les réalisent. Certes, en un sens, la prévision est un art tant elle dépend des signes précurseurs que nous livre le présent, de l’interprétation des évolutions en cours, de la capacité des économistes de sélectionner les informations pertinentes parmi celles, multiples, dont l’intérêt n’est qu’anecdotique. Mais elle est surtout une science puisqu’elle consiste à déduire des informations dont on dispose sur le présent une vision de l’avenir. Elle ne peut être formulée en dehors d’un cadre général d’interprétation, c’est-à-dire d’une théorie qui met en relation les informations que l’on privilégie et les variables que l’on cherche à prévoir. [Premier paragraphe

Not lesser but Greater fractional anisotropy in adolescents with alcohol use disorders

AbstractObjectiveThe objective of this study is to examine white matter microstructure using diffusion tensor imaging (DTI) in a sample of adolescents with alcohol use disorders (AUD) and no psychiatric or substance co-morbidity.MethodsFifty adolescents with AUD and fifty non-alcohol abusing controls matched on gender and age were studied with DTI, neurocognitive testing, and a clinical assessment that included measures of alcohol use and childhood trauma. Maps of fractional anisotropy (FA) and mean diffusivity (MD) were computed, registered to a common template, and voxel-wise statistical analysis used to assess group differences. Associations between regions of altered WM microstructure and clinical or neurocognitive measures were also assessed.ResultsCompared with controls, adolescent drinkers without co-morbid substance abuse or externalizing disorder, showed 1) no regions of significantly lower FA, 2) increased FA in WM tracts of the limbic system; 3) no MD differences; and 4) within the region of higher FA in AUD, there were no associations between FA and alcohol use, cognition, or trauma.DiscussionThe most important observation of this study is our failure to observe significantly smaller FA in this relatively large alcohol abuse/dependent adolescent sample. Greater FA in the limbic regions observed in this study may index a risk for adolescent AUD instead of a consequence of drinking. Drinking behavior may be reinforced in those with higher FA and perhaps greater myelination in these brain regions involved in reward and reinforcement

Débat sur les perspectives économiques à court terme du 16 octobre 2003

Les prévisions occupent une place particulière dans le débat public en économie. Elles sont généralement considérées comme des prédictions, qualifiées fréquemment d’optimistes ou de pessimistes, comme si elles dépendaient de l’humeur des équipes qui les réalisent. Certes, en un sens, la prévision est un art tant elle dépend des signes précurseurs que nous livre le présent, de l’interprétation des évolutions en cours, de la capacité des économistes de sélectionner les informations pertinentes parmi celles, multiples, dont l’intérêt n’est qu’anecdotique. Mais elle est surtout une science puisqu’elle consiste à déduire des informations dont on dispose sur le présent une vision de l’avenir. Elle ne peut être formulée en dehors d’un cadre général d’interprétation, c’est-à-dire d’une théorie qui met en relation les informations que l’on privilégie et les variables que l’on cherche à prévoir. [Premier paragraphe

How intramolecular hydrogen bonding (IHB) controls the C-ON bond homolysis in alkoxyamines

International audienceRecent amazing results (Nkolo et al., Org. Biomol. Chem., 2017, 6167) on the effect of solvents and polarity on the C-ON bond homolysis rate constants kd of alkoxyamine R1R2NOR3 led us to re-investigate the antagonistic effect of intramolecular hydrogen-bonding (IHB) on kd. Here, IHB is investigated both in the nitroxyl fragment R1R2NO and in the alkyl fragment R-3, as well as between fragments, that is, the donating group on the alkyl fragment and the accepting group on the nitroxyl fragment, and conversely. It appears that IHB between fragments (inter IHB) strikingly decreases the homolysis rate constant kd, whereas IHB within the fragment (intra IHB) moderately increases kd. For one alkoxyamine, the simultaneous occurrence of IHB within the nitroxyl fragment and between fragments is reported. The protonation effect is weaker in the presence than in the absence of IHB. A moderate solvent effect is also observed

Art-175 is a highly efficient antibacterial against multidrug-resistant strains and persisters of Pseudomonas aeruginosa

Artilysins constitute a novel class of efficient enzyme-based antibacterials. Specifically, they covalently combine a bacteriophage-encoded endolysin, which degrades the peptidoglycan, with a targeting peptide that transports the endolysin through the outer membrane of Gram-negative bacteria. Art-085, as well as Art-175, its optimized homolog with increased thermostability, are each composed of the sheep myeloid 29-amino acid (SMAP-29) peptide fused to the KZ144 endolysin. In contrast to KZ144, Art-085 and Art-175 pass the outer membrane and kill Pseudomonas aeruginosa, including multidrug-resistant strains, in a rapid and efficient (similar to 5 log units) manner. Time-lapse microscopy confirms that Art-175 punctures the peptidoglycan layer within 1 min, inducing a bulging membrane and complete lysis. Art-175 is highly refractory to resistance development by naturally occurring mutations. In addition, the resistance mechanisms against 21 therapeutically used antibiotics do not show cross-resistance to Art-175. Since Art-175 does not require an active metabolism for its activity, it has a superior bactericidal effect against P. aeruginosa persisters (up to > 4 log units compared to that of the untreated controls). In summary, Art-175 is a novel antibacterial that is well suited for a broad range of applications in hygiene and veterinary and human medicine, with a unique potential to target persister-driven chronic infections

Interpretation of health-related quality of life outcomes in Parkinson's disease from the EARLYSTIM Study.

The EARLYSTIM Study compared deep brain stimulation (DBS) with best medical treatment (BMT) over 2-years, showing a between-group difference of 8.0 from baseline in favor of DBS in health-related quality of life (HRQoL), measured with the PDQ-39 SI (summary index). This study obtained complementary information about the importance of the change in HRQoL as measured by the PDQ-39, using anchor-based (Patient Global Impression of Change, PGIC) and distribution-based techniques (magnitude of change, effect size, thresholds, distribution of benefit) applied to the EARLYSTIM study data. Anchor-based techniques showed a difference follow-up-baseline for patients who reported "minimal improvement" of -5.8 [-9.9, -1.6] (mean [95%CI]) in the DBS group vs -2.9 [-9.0, 3.1] in the BMT group. As the vast majority (80.8%) of DBS patients reported "much or very much improvement", this difference was explored for the latter group and amounted to -8.7 for the DBS group and -6.5 in the BMT group. Distribution-based techniques that analyzed the relative change and treatment effect size showed a moderate benefit of the DBS on the HRQoL, whereas a slight worsening was observed in the BMT group. The change in the DBS group (-7.8) was higher than the MIC (Minimally Important Change) estimated value (-5.8 by the anchor; -6.3 by triangulation of thresholds), but not in the BMT (0.2 vs. -3.0 to -5.4, respectively). Almost 90% of the patients in the DBS group declared some improvement (58.3% and 56.7% beyond the estimated MIC), which was significantly different from the BMT group whose proportions were 32.0% and 30.3%, respectively. The number needed to treat to improve ≥1 MIC by DBS vs BMT was 3.8. Change in depression, disability and pain influenced the improvement of the DBS group. DBS improved HRQoL in a high proportion of patients to a significant and moderate degree, at 2 years follow-up

Modulation of the ATM/autophagy pathway by a G-quadruplex ligand tips the balance between senescence and apoptosis in cancer cells

G-quadruplex ligands exert their antiproliferative effects through telomere-dependent and telomere-independent mechanisms, but the inter-relationships among autophagy, cell growth arrest and cell death induced by these ligands remain largely unexplored. Here, we demonstrate that the G-quadruplex ligand 20A causes growth arrest of cancer cells in culture and in a HeLa cell xenografted mouse model. This response is associated with the induction of senescence and apoptosis. Transcriptomic analysis of 20A treated cells reveals a significant functional enrichment of biological pathways related to growth arrest, DNA damage response and the lysosomal pathway. 20A elicits global DNA damage but not telomeric damage and activates the ATM and autophagy pathways. Loss of ATM following 20A treatment inhibits both autophagy and senescence and sensitizes cells to death. Moreover, disruption of autophagy by deletion of two essential autophagy genes ATG5 and ATG7 leads to failure of CHK1 activation by 20A and subsequently increased cell death. Our results, therefore, identify the activation of ATM by 20A as a critical player in the balance between senescence and apoptosis and autophagy as one of the key mediators of such regulation. Thus, targeting the ATM/autophagy pathway might be a promising strategy to achieve the maximal anticancer effect of this compound

Landscape design for soil conservation under land use and climate change

International audienceSoils and landscapes evolve simultaneously. Soil evolution is controlled by redistribution and transformation processes influenced by topographic and climatic parameters, with also a major contribution of management strategies. The perennial landscape features have a strong influence on soil spatial distribution (geometry) and soil genesis. Building landscapes which enhance soil resilience to degradation processes and increase soil services appears as a promising way to adapt to forthcoming climatic and land use evolutions. The presentation aims to synthetize major results from a research program nicknamed Landsoil which focused on the evolution of agricultural soils over medium time scales (decades to centuries) in relation to changing conditions of land use and climate. Precise study of the soil 3D organization in three contrasted landscapes (Brittany, Touraine, Languedoc-Roussillon) enabled to link soil redistribution in space to landscape components (field geometry, hedges or ditches network) and their past evolution. A dynamic and high resolution spatial modeling approach was developed coupling erosion processes and soil organic matter evolution and was calibrated over past evolution using dating techniques (Cs137, C14, OSL). The resulting Landsoil model was afterwards applied in a prospective manner under different scenarios of land use and climate change over the 21th century. Indicators of soil vulnerability and soil resilience were defined and tested by the comparison of several prospective scenarios applied on a same landscape and by comparison of the contrasted landscapes