Outcomes of elective liver surgery worldwide: a global, prospective, multicenter, cross-sectional study

Background: The outcomes of liver surgery worldwide remain unknown. The true population-based outcomes are likely different to those vastly reported that reflect the activity of highly specialized academic centers. The aim of this study was to measure the true worldwide practice of liver surgery and associated outcomes by recruiting from centers across the globe. The geographic distribution of liver surgery activity and complexity was also evaluated to further understand variations in outcomes. Methods: LiverGroup.org was an international, prospective, multicenter, cross-sectional study following the Global Surgery Collaborative Snapshot Research approach with a 3-month prospective, consecutive patient enrollment within January–December 2019. Each patient was followed up for 90 days postoperatively. All patients undergoing liver surgery at their respective centers were eligible for study inclusion. Basic demographics, patient and operation characteristics were collected. Morbidity was recorded according to the Clavien–Dindo Classification of Surgical Complications. Country-based and hospital-based data were collected, including the Human Development Index (HDI). (NCT03768141). Results: A total of 2159 patients were included from six continents. Surgery was performed for cancer in 1785 (83%) patients. Of all patients, 912 (42%) experienced a postoperative complication of any severity, while the major complication rate was 16% (341/2159). The overall 90-day mortality rate after liver surgery was 3.8% (82/2,159). The overall failure to rescue rate was 11% (82/ 722) ranging from 5 to 35% among the higher and lower HDI groups, respectively. Conclusions: This is the first to our knowledge global surgery study specifically designed and conducted for specialized liver surgery. The authors identified failure to rescue as a significant potentially modifiable factor for mortality after liver surgery, mostly related to lower Human Development Index countries. Members of the LiverGroup.org network could now work together to develop quality improvement collaboratives

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

L'évolution des vaccins contre la rage humaine et la contribution majeure de Tadeusz Wiktor

Malgré la présence continue du risque d'infection rabique dans de nombreuses parties du globe, la vaccination montra depuis longtemps son potentiel en sauvant de nombreuses vies. Les raisons d'une mortalité élevée suite à l'infection rabique sont essentiellement liées à un défaut de vaccination de post-exposition ou d'un retard de cette administration. La carrière de Tadeusz Wiktor, un des pionniers de la recherche moderne contre la rage, s'inscrit dans cette démarche. Il est né dans la Pologne de l'entre-deux guerres puis, en 1942, intégra l'Ecole Vétérinaire de Lyon qui fut le point de départ de sa prodigieuse carrière. Au début des années 1960, suite à la rencontre d'Hilary Koprowski, Tadeusz Wiktor rejoignit l'Institut Wistar à Philadelphie, premier centre américain de recherche biomédicale. Il développa avec succès un vaccin humain très efficace et parfaitement toléré, adapté sur des cultures de cellules diploïdes humaines WI-38. En 1965, le Dr Charles Mérieux offrit la collaboration de l'Institut Mérieux à l'équipe du Wistar, lors du symposium Rabies organisé à l'abbaye de Talloires. L'Institut Mérieux (devenu Sanofi Pasteur) développa, à partir de 1985, le nouveau vaccin sur culture de cellules Vero, plus économique car produit avec les moyens de culture en fermenteur. Enfin, au début des années 1980, Wiktor et l'équipe du Wistar participèrent à la mise au point du premier vaccin recombinant utilisable chez les animaux. Il fut utilisé avec succès pour les vacciner (essentiellement les renards) à l'aide d'appâts largués par hélicoptères. En conclusion, le travail de Tadeusz Wiktor ouvrit la voie des vaccins antirabiques modernes, à la fois, pour usage vétérinaire et humain.LYON1-BU Santé (693882101) / SudocSudocFranceF

Population heterogeneity in associations between hormonal contraception and antidepressant use in Sweden : a prospective cohort study applying intersectional multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA)

OBJECTIVES: From a reproductive justice framework, we aimed to investigate how a possible association between hormonal contraceptive (HC) and antidepressants use (as a proxy for depression) is distributed across intersectional strata in the population. We aimed to visualise how intersecting power dynamics may operate in combination with HC use to increase or decrease subsequent use of antidepressants. Our main hypothesis was that the previously observed association between HC and antidepressants use would vary between strata, being more pronounced in more oppressed intersectional contexts. For this purpose, we applied an intersectional multilevel analysis of individual heterogeneity and discriminatory accuracy approach.DESIGN: Observational prospective cohort study using record linkage of national Swedish registers.SETTING: The population of Sweden.PARTICIPANTS: All 915 954 women aged 12-30 residing in Sweden 2010, without a recent pregnancy and alive during the individual 1-year follow-up.PRIMARY OUTCOME MEASURE: Use of any antidepressant, meaning being dispensed at least one antidepressant (ATC: N06A) during follow-up.RESULTS: Previously mentally healthy HC users had an OR of 1.79 for use of antidepressants compared with non-users, whereas this number was 1.28 for women with previous mental health issues. The highest antidepressant use were uniformly found in strata with previous mental health issues, with highest usage in women aged 24-30 with no immigrant background, low income and HC use (51.4%). The largest difference in antidepressant use between HC users and non-users was found in teenagers, and in adult women of immigrant background with low income. Of the total individual variance in the latent propensity of using antidepressant 9.01% (healthy) and 8.16% (with previous mental health issues) was found at the intersectional stratum level.CONCLUSIONS: Our study suggests teenagers and women with immigrant background and low income could be more sensitive to mood effects of HC, a heterogeneity important to consider moving forward

Chemical evolution of Titan's tholins exposed to solar radiation in Low Earth Orbit onboard the EXPOSE facility and possible incidence on Titan's aerosols composition (Screen 5)

International audienceWith the objective to characterize the aging of Titan's aerosols produced in the upper atmosphere and submitted to solar radiation during their long descent to the satellite surface, Titan's tholins were exposed to the direct solar radiation in low Earth orbit using the ESA's EXPOSE facility that was mounted outside the ISS for months. The interest of such an experiment comes from the exposure of the sample to the real solar radiation spectrum. Two varieties of tholins with different chemical properties were produced with the PAMPRE laboratory experiment, one using a (98:2) N2:CH4 gaseous mixture, and another one with a (90:10) mixture. These samples were exposed to the same solar radiation for the months the EXPOSE facility was mounted outside ISS. Their chemical properties measured before the flight and after their return to the laboratory were compared. Results clearly show that both tholins structure have been modified by the solar radiation. Thanks to control samples placed in the EXPOSE facility in blind cells, and in a facility in the laboratory, this evolution can be definitely attributed to UV radiation. We present here the corresponding results and the consequences we can deduce for the aging of the Titan'

Chemical Aging of Titan's Tholins Exposed to Solar Radiation in Low Earth Orbit onboard the EXPOSE Facility

International audienceTitan's organic aerosols are produced from the chemistry occurring in the atmosphere from gaseous N2 and CH4 submitted to UV solar radiation and energetic particles from Saturn magnetosphere. Our direct knowledge about their chemical composition is limited but we know they are among the most complex organic materials on Titan, composed of a solid core incorporating at least both carbon, hydrogen and nitrogen atoms. This chemistry is unique in the solar system and it could help understanding pathways of the prebiotic chemistry that resulted in the emergence of life. Titan's aerosols composition is indirectly studied through the production and analysis of analogues, called tholins, using laboratory experiments which mimic Titan's atmosphere chemistry conditions. But usually, these tholins are analyzed straight after their production, and it is only recently that the question of their aging was raised. In particular, the aging of the Titan's aerosols submitted to solar radiation during their long descent to the satellite surface was studied in the laboratory using specific UV wavelengths (1). With the same objective, Titan's tholins were exposed to the direct solar radiation in low Earth orbit using the ESA's EXPOSE facility mounted outside the ISS for months. Two varieties of tholins with different chemical properties were produced with the PAMPRE laboratory experiment (2), the first one using a (98:2) N2:CH4 gaseous mixture, and the other one, a (90:10) one. Increasing the amount of initial methane results in a more aliphatic material. These samples were exposed to the same solar radiation for the months the EXPOSE facility was mounted outside ISS. The chemical properties of these samples measured before the flight and after their return to the laboratory were compared. They clearly showed that both tholins structure have been modified in some extent by the solar radiation. Thanks to control samples placed in the EXPOSE facility in blind cells, and in a facility in the laboratory, this evolution can be definitely attributed to UV radiation. We present here the corresponding results and the consequences we can deduce for the aging of the Titan's aerosols Ref:[1]Carrasco N.(2018) Nat. Ast. [2] Szopa C. (2005) Planet. Space Sci

Chemical evolution of Titan's tholins exposed to solar radiation in Low Earth Orbit onboard the EXPOSE facility and possible incidence on Titan's aerosols composition (Screen 5)

International audienceWith the objective to characterize the aging of Titan's aerosols produced in the upper atmosphere and submitted to solar radiation during their long descent to the satellite surface, Titan's tholins were exposed to the direct solar radiation in low Earth orbit using the ESA's EXPOSE facility that was mounted outside the ISS for months. The interest of such an experiment comes from the exposure of the sample to the real solar radiation spectrum. Two varieties of tholins with different chemical properties were produced with the PAMPRE laboratory experiment, one using a (98:2) N2:CH4 gaseous mixture, and another one with a (90:10) mixture. These samples were exposed to the same solar radiation for the months the EXPOSE facility was mounted outside ISS. Their chemical properties measured before the flight and after their return to the laboratory were compared. Results clearly show that both tholins structure have been modified by the solar radiation. Thanks to control samples placed in the EXPOSE facility in blind cells, and in a facility in the laboratory, this evolution can be definitely attributed to UV radiation. We present here the corresponding results and the consequences we can deduce for the aging of the Titan'

Evolution of organic molecules under Mars-like UV radiation conditions in space and laboratory

International audienceThe detection and identification of organic molecules at Mars are of prime importance, as some of these molecules are life precursors and components. While in situ planetary missions are searching for them, it is essential to understand how organic molecules evolve and are preserved at the surface of Mars. Indeed the harsh conditions of the environment of Mars such as ultraviolet (UV) radiation or oxidative processes could explain the low abundance and diversity of organic molecules detected by now [1]. In order to get a better understanding of the evolution of organic matter at the surface of Mars, we exposed organic molecules under a Mars-like UV radiation environment. Similar organic samples were exposed to the Sun radiation, outside the International Space Station (ISS), and under a UV lamp (martian pressure and temperature conditions) in the laboratory