LE NANNOPLANCTON CALCAIRE ET LA FORMATION DES ALTERNANCES CALCAIRES-MARNES DANS LE LIAS DES BASSINS DE MARCHES-OMBRIE (ITALIE)

In the classical sections of Sentino-Valdorbia, Bosso and the Marne di Monte Serrone type-section the rhythmic, limestone/marl sedimentation of the following formations were studied: the Corniola (Late Sinemurian to Earliest Toarcian) and the Marne di Monte Serrone (Early Toarcian). The geological framework is drawn from the numerous and significant published papers which give a good stratigraphical scheme and a precise paleogeographic setting. The limestones have been studied in thin sections (texture, occurrence and abundance of schizospheres, other fauna, etc.) and with SEM (structure, occurrence, abundance and diagenetic state of schizospheres; coccoliths). Marly interbeds have been studied in light microscopy on smear slides of raw sediment to find out coccoliths and schizospheres and with SEM, both on washed and centrifuged sediments (for a better definition of the nannofloras) and on freshly broken surfaces. The conclusions are based upon 69 SEM pictures of limestones and 94 SEM pictures of marls from the Corniola Formation; on 169 SEM pictures of limestones and 303 SEM pictures of marls from the Marne di Monte Serrone Formation. The observations show the importance of the nannofloral contrast between the Limestone beds with schizospheres and the marly interbeds with coccoliths. The contrast is thought to portray rhe original difference between the components which generated the two different types of sediments. The lithogenetic role of the nannoplankton was strongly differentiated and was linked to an alternation of clay-poor, sea-warer phases when stable, calcareous nannoplankton (schizospheres) dominated and did not evolve and of clay-richer, sea-water phases when coccolithophorids expanded and evolved

Structural basis of envelope and phase intrinsic coupling modes in the cerebral cortex

Intrinsic coupling modes (ICMs) can be observed in ongoing brain activity at multiple spatial and temporal scales. Two families of ICMs can be distinguished: phase and envelope ICMs. The principles that shape these ICMs remain partly elusive, in particular their relation to the underlying brain structure. Here we explored structure-function relationships in the ferret brain between ICMs quantified from ongoing brain activity recorded with chronically implanted micro-ECoG arrays and structural connectivity (SC) obtained from high-resolution diffusion MRI tractography. Large-scale computational models were used to explore the ability to predict both types of ICMs. Importantly, all investigations were conducted with ICM measures that are sensitive or insensitive to volume conduction effects. The results show that both types of ICMs are significantly related to SC, except for phase ICMs when using measures removing zero-lag coupling. The correlation between SC and ICMs increases with increasing frequency which is accompanied by reduced delays. Computational models produced results that were highly dependent on the specific parameter settings. The most consistent predictions were derived from measures solely based on SC. Overall, the results demonstrate that patterns of cortical functional coupling as reflected in both phase and envelope ICMs are both related, albeit to different degrees, to the underlying structural connectivity in the cerebral cortex.This work was supported by funding from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - SFB 936 - 178316478 - A1 (C.C.H.), A2 (A.K.E.), and Z3 (C.C.H. and A.M.), SPP1665 - 220176618 - EN533/13-1 (A.K.E.), SPP2041 - 313856816 - HI1286/6-1 (C.C.H.) and EN533/15-1 (A.K.E.), from the European Unions Horizon 2020 Framework Programme for Research and Innovation under Specific Grant Agreements 785907 and 945539 (Human Brain Project SGA2 and SGA3, C.C.H.), and from the 2015 FLAG-ERA Joint Transnational Call for project FIIND - ANR-15-HBPR-0005 (R.T.).Peer reviewe

Influence of drug safety advisories on drug utilisation: an international interrupted time series and meta-analysis

OBJECTIVE: To evaluate the association between regulatory drug safety advisories and changes in drug utilisation. DESIGN: We conducted controlled, interrupted times series analyses with administrative prescription claims data to estimate changes in drug utilisation following advisories. We used random-effects meta-analysis with inverse-variance weighting to estimate the average postadvisory change in drug utilisation across advisories. STUDY POPULATION: We included advisories issued in Canada, Denmark, the UK and the USA during 2009-2015, mainly concerning drugs in common use in primary care. We excluded advisories related to over-the-counter drugs, drug-drug interactions, vaccines, drugs used primarily in hospital and advisories with co-interventions within ±6 months. MAIN OUTCOME MEASURES: Change in drug utilisation, defined as actual versus predicted percentage change in the number of prescriptions (for advisories without dose-related advice), or in the number of defined daily doses (for dose-related advisories), per 100 000 population. RESULTS: Among advisories without dose-related advice (n=20), the average change in drug utilisation was -5.83% (95% CI -10.93 to -0.73; p=0.03). Advisories with dose-related advice (n=4) were not associated with a statistically significant change in drug utilisation (-1.93%; 95% CI -17.10 to 13.23; p=0.80). In a post hoc subgroup analysis of advisories without dose-related advice, we observed no statistically significant difference between the change in drug utilisation following advisories with explicit prescribing advice, such as a recommendation to consider the risk of a drug when prescribing, and the change in drug utilisation following advisories without such advice. CONCLUSIONS: Among safety advisories issued on a wide range of drugs during 2009-2015 in 4 countries (Canada, Denmark, the UK and the USA), the association of advisories with changes in drug utilisation was variable, and the average association was modest

Hydroxyzine Initiation Following Drug Safety Advisories on Cardiac Arrhythmias in the UK and Canada: A Longitudinal Cohort Study

INTRODUCTION: Regulatory advisories on hydroxyzine and risk of QT prolongation and Torsade de pointes (TdP) were issued in the UK in April 2015 and Canada in June 2016. We hypothesized patients with risk factors for QT prolongation and TdP, compared with those without risk factors, would be less likely to initiate hydroxyzine in the UK and in British Columbia (BC), Canada, following advisories. METHODS: We conducted a longitudinal study with repeated measures, and evaluated hydroxyzine initiation in a UK cohort and a concurrent BC control cohort (April 2013-March 2016) as well as in a BC advisory cohort (June 2014-May 2017). RESULTS: This study included 247,665 patients in the UK cohort, 297,147 patients in the BC control cohort, and 303,653 patients in the BC advisory cohort. Over a 12-month post-advisory period, hydroxyzine initiation decreased by 21% in the UK (rate ratio 0.79, 95% confidence interval 0.66-0.96) relative to the expected level of initiation based on the pre-advisory trend. Hydroxyzine initiation did not change in the BC control cohort or following the Canadian advisory in the BC advisory cohort. The decrease in hydroxyzine initiation in the UK in the 12 months after the advisories was not significantly different for patients with risk factors compared with those without risk factors. CONCLUSION: Hydroxyzine initiation decreased in the UK, but not in BC, in the 12 months following safety advisories. The decrease in hydroxyzine initiation in the UK was not significantly different for patients with versus without risk factors for QT prolongation and TdP

Brain simulation as a cloud service: The Virtual Brain on EBRAINS

The Virtual Brain (TVB) is now available as open-source services on the cloud research platform EBRAINS (ebrains.eu). It offers software for constructing, simulating and analysing brain network models including the TVB simulator; magnetic resonance imaging (MRI) processing pipelines to extract structural and functional brain networks; combined simulation of large-scale brain networks with small-scale spiking networks; automatic conversion of user-specified model equations into fast simulation code; simulation-ready brain models of patients and healthy volunteers; Bayesian parameter optimization in epilepsy patient models; data and software for mouse brain simulation; and extensive educational material. TVB cloud services facilitate reproducible online collaboration and discovery of data assets, models, and software embedded in scalable and secure workflows, a precondition for research on large cohort data sets, better generalizability, and clinical translation

From bi-polar to regional distribution of modern dinoflagellate cysts, an overview of their biogeography

This paper examines the distribution of 91 modern dinoflagellate cyst taxa from 3636 locations across the world's oceans. Patterns of distributions among the taxa included bi-polarity, cosmopolitan, northern versus southern hemispheres ,and geographically restricted. Of the 91 taxa, three dominate these 3636 assemblages at the global scale, Brigantedinium species, Operculodinium centrocarpum sensu Wall and Dale 1966 and some species of Spiniferites. Whereas Brigantediniumis a true cosmopolitan taxon, with high abundances in each ocean, Operculodinium centrocarpum sensu Wall and Dale 1966 shows high abundances in polar to temperate regions in the Northern Hemisphere,and in tropical to sub-tropical waters in the Southern Hemisphere. Spiniferites species show highest occurrences in the Southern Hemisphere. This study also highlights three true bi-polar species,Impagidinium pallidum, Islandinium minutum and cyst of Polarella glacialis. Only a few taxa are strictl yendemic, either being relics of ancient seas such as the Paratethys (Spiniferitescruciformis) or linked to specific environmental conditions. However, recent studies have shown recent worldwide dispersal of these endemic species possibly due to human activities. Overall, this compilation has highlighted the progress made since the early 1970s on our understanding of these important tracers of environmental conditions but also gaps in our knowledge of their distribution in pelagic regions of the Pacific and Indian Oceans as well as under Arctic sea ice

Com o diabo no corpo: os terríveis papagaios do Brasil colônia

Desde a Antiguidade, papagaios, periquitos e afins (Psittacidae) fascinaram os europeus por seu vivo colorido e uma notável capacidade de interação com seres humanos. A descoberta do Novo Mundo nada faria além de acrescentar novos elementos ao tráfico de animais exóticos há muito estabelecido pelos europeus com a África e o Oriente. Sem possuir grandes mamíferos, a América tropical participaria desse comércio com o que tinha de mais atrativo, essencialmente felinos, primatas e aves - em particular os papagaios, os quais eram embarcados em bom número. Contudo, a julgar pelos documentos do Brasil colônia, esses voláteis podiam inspirar muito pouca simpatia, pois nenhum outro animal - exceto as formigas - foi tantas vezes mencionado como praga para a agricultura. Além disso, alguns psitácidas mostravam-se tão loquazes que inspiravam a séria desconfiança de serem animais demoníacos ou possessos, pois só três classes de entidades - anjos, homens e demônios - possuíam o dom da palavra. Nos dias de hoje, vários representantes dos Psittacidae ainda constituem uma ameaça para a agricultura, enquanto os indivíduos muito faladores continuam despertando a suspeita de estarem possuídos pelo demônio. Transcendendo a mera curiosidade, essa crença exemplifica o quão intrincadas podem ser as relações do homem com o chamado “mundo natural”, revelando um universo mais amplo e multifacetado do que se poderia supor a princípio. Nesse sentido, a existência de aves capazes de falar torna essa relação ainda mais complexa e evidencia que as dificuldades de estabelecer o limite entre o animal e o humano se estendem além dos primatas e envolvem as mais inusitadas espécies zoológicas.Since ancient times, parrots and their allies (Psittacidae) have fascinated Europeans by their striking colors and notable ability to interact with human beings. The discovery of the New World added new species to the international exotic animal trade, which for many centuries had brought beasts to Europe from Africa and the Orient. Lacking large mammals, tropical America participated in this trade with its most appealing species, essentially felines, primates and birds - especially parrots - which were shipped in large numbers. It should be noted, however, that at times these birds were not well liked. In fact, according to documents from colonial Brazil, only the ants rank higher than parrots as the animals most often mentioned as agricultural pests. On the other hand, some of these birds were so chatty that people suspected them to be demonic or possessed animals, since only three classes of beings - angels, men and demons - have the ability to speak. Nowadays, several Psittacidae still constitute a threat to agriculture, and the suspicion that extremely talkative birds were demon possessed has also survived. More than a joke or a mere curiosity, this belief exemplifies how intricate man’s relationships with the “natural world” may be. In this sense, the existence of birds that are able to speak adds a further twist to these relationships, demonstrating that the problem of establishing a boundary between the animal and the human does not only involve primates, but also includes some unusual zoological species

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Evaluation des prescriptions de risperidone à libération prolongée au centre psychothérapique de Nancy entre 2005 et 2008

Les neuroleptiques à action prolongée constitue le traitement de référence du patient schizophrène non observant. En mars 2005, la rispéridone à libération prolongée (RisperdalConsta® LP), premier antipsychotique de deuxième génération à action prolongée, a été commercialisée, combinant ainsi les avantages d un neuroleptique à action prolongée à ceux d un antipsychotique de deuxième génération et modifiant les conditions de prise en charge du patient schizophrène non observant.L objectif de ce mémoire est de réaliser une évaluation des prescriptions de Risperdalconsta® LP depuis sa mise à disposition des services de soins au Centre Psychothérapique de Nancy (CPN).Le recueil des informations s est fait à partir des relevés nominatifs de dispensation du Risperdalconsta® LP, des prescriptions informatisées et du dossier médical des patients. Le bilan d utilisation de ce médicament au CPN a été réalisé sur une période de 39 mois. La part du RisperdalConsta® LP dans le budget médicament du CPN a été évaluée : elle a augmenté entre 2005 et 2008 et représente actuellement 16% de ce budget. L évaluation des prescriptions de RisperdalConsta® LP a été effectuée en tenant compte des recommandations d utilisation de ce produit. D avril 2005 à juin 2008, 238 patients ont reçu au moins une injection de RisperdalConsta® LP au CPN. Parmi eux, 72% étaient traités pour un trouble mental de la catégorie F20-F29 (schizophrénie, trouble schizotypique et troubles délirants) et 49% pour schizophrénie : ce qui est en conformité avec les indications du RCP du RisperdalConsta® LP. Le RisperdalConsta® LP a été utilisé au long cours au CPN chez 33 des 238 patients. Lors de l instauration du traitement, l équivalence posologique entre rispéridone per os et le RisperdalConsta® LP ainsi que la durée de chevauchement entre les deux formes de rispéridone ont été conformes au RCP du RisperdalConsta® LP chez un peu plus de la moitié des patients. La prescription d un correcteur de TEP au cours du traitement par RisperdalConsta® LP a eu lieu chez 37% des patients, mais seuls 13% ont bénéficié d une instauration de traitement par correcteur de TEP. L arrêt du RisperdalConsta® LP a eu lieu chez 93 des 238 patients et pour 50% d entre eux dans les six premiers mois de traitement par RisperdalConsta® LP.Le bon usage d un traitement par neuroleptique à action prolongée est d autant plus important qu il diminue le risque de rechute chez des patients schizophrènes non observants. Cependant, il est important de garder à l esprit que la seule utilisation d un neuroleptique retard n est pas suffisante pour réduire le risque de survenue d une éventuelle nouvelle décompensation psychotique. En effet, la prise en charge thérapeutique de la schizophrénie est non seulement pharmacologique, mais aussi psychologique et sociale.NANCY1-SCD Pharmacie-Odontologie (543952101) / SudocNANCY1-Bib. numérique (543959902) / SudocSudocFranceF

Agir humain et détachement chez Maître Eckhart

Le détachement (abegescheidenheit) est un terme forgé par Eckhart et constitue l'axe principal de sa prédication en moyen-haut-allemand. Il s'agit d'un travail de libération par rapport à toutes choses et à soi-même, mais aussi d'une expérience de la grâce conduisant à une réalisation de l'homme dans son être propre. A ce titre, le détachement n'est pas une fuite du monde, mais bien au contraire la condition et le fondement d'un agir proprement humain comme le manifeste tout particulièrement l'acte de la parole. La pensée eckhartienne s'inscrit ainsi dans la tradition théologique et reprend un certain nombre de thèmes classiques comme par exemple celui de l'Incarnation du Verbe et de la divinisation de l'homme, ou encore le schème augustinien de la liberté et de la grâce. Cette articulation entre détachement et agir doit également être située par rapport au contexte historique. A la fin du Moyen Age, on assiste en effet à un renouveau de la vie spirituelle et en particulier à un essor des pratiques ascétiques et pénitentielles. Les gens veulent savoir ce qu'il faut faire pour être en " bons termes " avec Dieu. Par-delà les considérations morales de bien et de mal, de péché et de vertu, Eckhart répond à ces préoccupations en montrant le fondement mystique de l'agir humain. En même temps, la dimension pratique du détachement lui permet de dénoncer les faux spirituels et les thèses développées par les disciples du Libre esprit qui envisagent la perfection comme une forme d'indifférence par rapport à la pratique des œuvres. Nourri de la tradition et enraciné dans les polémiques de son temps. Eckhart interroge également notre époque et l'étude de sa pensée s'avère féconde pour comprendre aujourd'hui certains auteurs comme Maurice Zundel, ce qui explique en partie l'engouement contemporain pour celui qui est peut-être encore un maître de vie (lebemeister).STRASBOURG-B.N.U.S. (674821001) / SudocSTRASBOURG-Théologie Catho. (674822201) / SudocSTRASBOURG-Théologie Protest. (674822202) / SudocSudocFranceF