Evaluation of prophylactic dosages of Enoxaparin in non-surgical elderly patients with renal impairment

BACKGROUND: Thromboprophylaxis dosing strategies using enoxaparin in elderly patients with renal disease are limited, while dose adjustments or monitoring of anti-Xa levels are recommended. We sought to evaluate the efficacy and safety of enoxaparin 20 mg versus 30 mg subcutaneously daily by comparing anti-Xa levels, thrombosis and bleeding. METHODS: We conducted a prospective, single-blinded, single-center randomized clinical trial including non-surgical patients, 70 years of age or older, with renal disease requiring thromboprophylaxis. Patients were randomized to receive either 20 mg or 30 mg of enoxaparin. The primary endpoint was peak anti-Xa levels on day 3. Secondary endpoints included trough anti-Xa levels on day 3, achievement of within range prophylactic target peak anti-Xa levels and the occurrence of hemorrhage, thrombosis, thrombocytopenia or hyperkalemia during hospitalization. RESULTS: Thirty-two patients were recruited and sixteen patients were randomized to each arm. Mean peak anti-Xa level was significantly higher in 30 mg arm (n = 13) compared to the 20 mg arm (n = 11) 0.26 +/- 0.11, 95%CI (0.18-0.34), versus 0.14 +/- 0.09, 95CI (0.08-0.19) UI/ml, respectively; p = 0.004. Mean trough anti-Xa level was higher in 30 mg arm (n = 10) compared to the 20 mg arm (n = 16), 0.06 +/- 0.03, 95CI (0.04-0.08) versus 0.03 +/- 0.03, 95CI (0.01-0.05) UI/ml, respectively; p = 0.044. Bleeding events reported in the 30 mg arm were one retroperitoneal bleed requiring multiple transfusions, and in the 20 mg arm one hematuria. No thrombotic events were reported. CONCLUSION: Peak anti-Xa levels provided by enoxaparin 20 mg were lower than the desired range for thromboprophylaxis in comparison to enoxaparin 30 mg. TRIAL REGISTRATION: The trial was retrospectively registered on ClinicalTrials.gov identifier: NCT03158792 . Registered: May 18, 2017

Catalytic mononitration of phenol using iso-propyl nitrate over zeolite catalysts

Mononitration of phenol was investigated using iso-propyl nitrate as a nitrating agent over various zeolite catalysts under different reaction conditions. Zeolite Hβ with a low Si/Al ratio (12.5) was found to be an active catalyst for nitration of phenol under reflux conditions in dichloroethane, producing 2- and 4-nitrophenols in a ratio of around 1:1. However, zeolites H-mordenite, HY and Hβ (with high Si/Al ratio—150 or 300) gave 2-nitrophenol as the major product (ortho/para ratio = ca. 2–3)

Mathematization of experts knowledge: example of part orientation in additive manufacturing

The use of expert knowledge by manufacturing companies to support everyday activities has become an emerging practice thanks to the new knowledge management tools. A big set of knowledge is available in the organizations but its profitable use to solve problems and assist decision making is still a challenge. This is the case of CAM operations or preprocessing steps for which various works have been led to involve experts’ knowledge in the decision-making based on qualitative principles. However, so far, there is no methodology to the quantitative representation of that knowledge for more assistance. This paper introduces an approach for the conversion of knowledge into quantitative mathematical models. The main idea is to go from elicitation data in the form of action rules to simple unitary mathematical images; here desirability functions. The whole process carried out to extract the useful information that help building the desirability functions is exposed and different useful mathematical considerations are proposed. The resulting methodology identifies the categories of concepts in action rules and translate them into codified action rules. Then, through a mathematization process, the desirability functions are built. In short, this new approach allows evaluating the satisfaction level of the rules prescribed by the experts. As an illustration, the model is applied to action rules for CAM operations in additive manufacturing and more precisely to the definition of part orientation. This has shown the robustness of the methodology used and that it is possible to translate elicitation data into mathematical functions operable in computation algorithms.ANR-17-CE10-0008 : COFF

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Microcirculatory alterations in sepsis : study of the sympatho-vagal balance and the effects of modulators of sympathetic system

Parmi les facteurs intervienant dans la régulation et le maintien du fonctionnement d'organes, le système nerveux autonome et la microcirculation jouent un rôle prépondérant. Chez les patients critiques, comme les patients en sepsis, des altérations de la balance sympatho-vagale et de la perfusion tissulaire peuvent survenir et avoir des conséquences majeures en matière de morbidité et mortalité. La mise en oeuvre de méthodes de détection précoces de ces perturbations pourrait donc contribuer à améliorer la survie des patients à risque. En effet, le suivi des paramètres hémodynamiques, comme classiquement réalisé lors de réanimation, peut s'avérer insuffisant pour détecter des altérations de perfusion tissulaire : lors de sepsis, des altérations microcirculatoires peuvent persister en dépit de la normalisation des paramètres macrocirculatoires et sont associées à un mauvais pronostic. Eu égard à la présence de dysfunctions microcirculatoires et du système nerveux autonome chez les patients critiques, ce travail de recherche s'est proposé d'évaluer l’impact de modulateurs du système sympathique sur la balance sympatho-vagale et la microcirculation. Pour ce faire, nous avons travaillé avec des modèles animaux et des animaux admis en centre hospitalier universitaire vétérinaire. Le suivi du système nerveux autonome s'est basé sur un nouvel index de mesure du tonus parasympathique (Parasympathetic Tone Activity ou PTA). En parallèle, la microcirculation a été évaluée par vidéomicroscopie (SDF, Sidestream Dark Field imaging). L'index PTA a démontré une performance correcte pour prédire les réactions hémodynamiques chez les chiens anesthésiés. Il a aussi permis de détecter une altération de la balance sympathique chez les chevaux admis pour une chirurgie de colique ainsi qu’une altération de la microcirculation en dépit des manoeuvres de réanimation. Les études précliniques sur l’impact de la perfusion d’esmolol et de dexmédétomidine dans un modèle porcin septique ont montré que, malgré leurs effets hémodynamiques potentiels, ces agents n’ont pas eu d’effet négatif sur la microcirculation. Ainsi, les résultats de ce travail suggèrent un effet bénéfique des modulateurs du système nerveux sympathique sur la microcicultion mais nécessite d'être confirmé à plus grande échelleAmong the factors involved in the regulation and maintenance of the organs’ functioning, the autonomic nervous system and the microcirculation play a preponderant role. In critical patients, such as septic patients, alterations in the sympathovagal balance and tissue perfusion may occur and have major consequences of morbidity and mortality. The implementation of early detection methods for these disturbances could therefore contribute to improve the survival of patients at risk. Indeed, the monitoring of hemodynamic parameters, as conventionally performed during resuscitation, may be insufficient to detect tissue perfusion alterations: during sepsis, microcirculatory changes may persist despite the normalization of macrocirculatory parameters and are associated with a bad prognosis. With regard to the presence of microcirculatory dysfunctions and autonomic nervous system alterations in critical patients, this research project proposed to evaluate the impact of modulators of the sympathetic system on the sympatho-vagal balance and microcirculation. In order to achieve this, we worked on animal models and animals admitted to the faculty’s veterinary hospital center. Monitoring of the autonomic nervous system was based on a new Parasympathetic Tone Activity (PTA) index. In parallel, the microcirculation was evaluated by videomicroscopy (SDF, Sidestream Dark Field imaging). The PTA index demonstrated a good performance in predicting hemodynamic reactions in anesthetized dogs. It also detected disturbances of the sympathetic balance in horses admitted for colic surgery as well as an alteration of microcirculation despite resuscitation maneuvers. Preclinical studies on the impact of esmolol and dexmedetomidine infusion in a septic swine model showed that, despite their potential hemodynamic effects, these agents did not have a negative effect on the microcirculation. Thus, these findings suggest a beneficial effect of the modulators of the sympathetic nervous system on the microcicultion, however, these resutls should be confirmed on a larger scal

KNOWLEDGE-BASED EVALUATION OF PART ORIENTATION DESIRABILITY IN POWDER BED FUSION ADDITIVE MANUFACTURING

International audienceAbstract In powder bed fusion (PBF) additive manufacturing, the definition of part orientation is one of the most important steps as it affects the quality, the cost and the build time of products. Different works already attempted to propose methodologies for the assessment of optimal build orientation based on criteria such as the minimization of support volume. Elicitation works with industry experts have shown that they use much more varied rules to determine the orientation of parts. For instance, they do not treat the different surfaces of the part the same way (e.g., experts state that “priority surfaces of the part must be oriented close to vertical”). Today, the available tools do not allow integrating these kind of specifications. This paper discusses a knowledge-based methodology for the evaluation of part candidate orientations in PBF. Desirability function approach is used to translate companies’ expertise in the form action rules into mathematical functions that are tested on geometries to provide metrics for assisting the decision-making. A case study is presented to illustrate the use of this desirability function approach on complex part orientation problem

Influence of feed salinity on ammonia recovery from high-strength effluents in transmembrane chemical absorption process

International audienc

Eight action rules for the orientation of additive manufacturing parts in powder bed fusion: an industry practice

International audienc