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

Investment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing in Africa over the past year has led to a major increase in the number of sequences that have been generated and used to track the pandemic on the continent, a number that now exceeds 100,000 genomes. Our results show an increase in the number of African countries that are able to sequence domestically and highlight that local sequencing enables faster turnaround times and more-regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and illuminate the distinct dispersal dynamics of variants of concern-particularly Alpha, Beta, Delta, and Omicron-on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve while the continent faces many emerging and reemerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

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

Clinical, pathophysiological, and prognostic factors associated with hemostasis-related complications during centrifugal pump-based short-term circulatory support

La problématique de cette thèse est la caractérisation des complications liées à l’hémostase chez le patient assisté par ECMO-VA périphérique afin d’en améliorer la prévention et de rationaliser les approches antithrombotiques en usage. Dans une première étude, nous avons décrit qualitativement et quantitativement la composition des thrombi formés sur les circuits d’ECMO-VA. Nous avons observé que ces thrombi sont majoritairement composés de VWF, de fibrine et dans une moindre proportion de plaquettes et d’érythrocytes. Notre approche quantitative a également permis de mettre en évidence la présence de NETs en l’absence de toute pathologie septique active, confirmant la possibilité d’une NETose aseptique sous ECMO-VA. Par une analyse en cluster hiérarchique, nous avons identifié 2 types de thrombi pouvant relever chacun d’un mécanisme de formation différent. Dans cette étude, la localisation des thrombi sur le circuit d’ECMO-VA n’impactait pas leurs compositions, ce qui souligne l’hétérogénéité des thrombi formés sous ECMO-VA et la multiplicité des mécanismes à l’origine de la thrombinoformation dans ce contexte. Dans un second travail, nous avons comparé la performance des revêtements de surfaces des circuits d’ECMO-VA à réduire la thrombinoforation et ses conséquences cliniques. Deux des revêtements les plus utilisés en routine étaient comparés : celle à base de phosphorylcholine et à base d’héparine. Nous avons observé un taux de complications thrombotiques plus conséquent dans le groupe phosphorylcholine sans surrisque hémorragique ou de mortalité dans les deux groupes. Par ailleurs, comparativement aux thrombi issus des jonctions de circuits traités par revêtement de phosphorylcholine, ceux provenant de circuits traités par polysaccharide-albumine étaient plus pauvres en VWF. Notre travail suggère que l’intensité de l’anticoagulation devrait être modulée en fonction du type de revêtement de surface du circuit d’ECMO. Notre troisième étude avait pour but d’identifier les saignements les plus graves justifiants d’une prise en charge clinique agressive et d’un investissement plus conséquent en recherche. À cette fin, nous avons comparé l’association entre 3 classifications de saignement avec la mortalité à 28 jours. La définition ELSO déjà en usage et les classes de la classification BARC ≥ type 2 étaient associées à la mortalité et retenues donc comme définitions de l’hémorragie majeure. Les facteurs biologiques prédictifs de l’hémorragie grave d’après la définition de l’ELSO étaient la baisse du fibrinogène, du compte plaquettaire et de l’hémoglobine à la canulation. L’indice de masse corporelle et l’étiologie postcardiotomie étaient également prédictifs de la survenue de cette complication. Dans un travail additionnel portant sur la thématique de la thèse, nous avons étudié deux des tests les plus utilisés pour la surveillance de l’héparinothérapie systémique sous ECMO, le TCA et l’activité Anti-Xa afin d’identifier le plus pertinent. Pour ce faire, dans un premier objectif nous avons étudié la relation entre ces deux tests puis avons analysé dans un second objectif l’impact de facteurs biologiques d’influences sur cette relation. Ensuite, nous avons déterminé leurs associations avec les complications thrombotiques et hémorragiques. Bien qu’étant linéairement associé, le taux de discordance entre leurs mesures était de 39 % pour une fenêtre référence d’Anti-Xa de 0,3 — 0,7 UI/mL. Ni le TCA et ni l’Anti-Xa n’étaient associées aux complications thrombotiques ou hémorragiques [...]The purpose of this dissertation is to characterize hemostasis-related complications in patients supported by peripheral VA-ECMO to improve their prevention and to optimize the antithrombotic therapeutic approaches in use. In a first study, we qualitatively and quantitatively described the composition of thrombi collected from the VA-ECMO circuits. We observed that these thrombi are mainly made of VWF, fibrin and in a lesser proportion of platelets and RBCs. Our quantitative approach also allowed us to demonstrate the presence of NETs while there was no active septic, confirming the possibility of aseptic NETosis under VA-ECMO. By hierarchical cluster analysis, we identified 2 types of thrombi, each of which may be related to a different mechanism of formation. In this study, the location of thrombi on the VA-ECMO circuit did not impact their compositions, highlighting the heterogeneity of thrombi formed within VA-ECMO and the multifactorial mechanisms that support thrombosis in this setting. In a second study, we compared the performance of surface coatings on VA-ECMO circuits to reduce thrombinoformation and its clinical consequences. Two of the most used coatings in daily practice were compared: the phosphorylcholin-based coating and the polysaccharide-albumin-based coating. We observed a higher rate of thrombotic complications in the phosphorylcholin group without any excess bleeding events or mortality in either group. In addition, compared with thrombi from phosphorylcholin-coated circuit junctions, those from polysaccharide-albumin-coated circuits were poorer in VWF. Our work suggests that the level of anticoagulation should be modulated according to the type of coating of the ECMO circuit.The aim of our third study was to identify the most relevant bleeding events that may guide clinical decision-making for more aggressive clinical management and a greater investment in research. To this end, we compared the association between 3 bleeding classifications with 28-day mortality. The ELSO definition already in use and the BARC classification classes ≥ type 2 were associated with 28-day mortality and thus retained as definitions of major bleeding. Laboratory parameters that are predictors major bleeding according to the ELSO definition were decreased fibrinogen, platelet count, and hemoglobin at cannulations. Body mass index and postcardiotomy etiology were also predictive of ELSO major bleeding. In an additional work related to the topic of the thesis, we studied two of the most used laboratory tests for the monitoring of systemic heparin during VA-ECMO, the APTT and the Anti-Xa activity, to identify the most relevant. First, we studied the relationship between these two tests and then analyzed in a second objective the impact of biological influencing factors on this relationship. Next, we determined their associations with thrombotic and hemorrhagic complications. Although linearly associated, the rate of discordance between their measurements was 39 % for an Anti-Xa reference range of 0.3 - 0.7 IU/mL. Neither APTT nor Anti-Xa was associated with thrombotic or bleeding complications. Taken together, our results highlight the heterogeneity of thrombi from peripheral VA-ECMO, the involvement of numerous causal factors that underline thrombotic and hemorrhagic complications, both not predictable by routine tests. Finally, our work underscored the need for new approaches in thrombotic or hemorrhagic complications management with targets set at an individual level considering both patient and ECMO circuit characteristics

Déterminants cliniques, physiopathologiques et pronostics associés aux complications liées à l’hémostase au cours des assistances circulatoires de courte durée à pompe centrifuge

The purpose of this dissertation is to characterize hemostasis-related complications in patients supported by peripheral VA-ECMO to improve their prevention and to optimize the antithrombotic therapeutic approaches in use. In a first study, we qualitatively and quantitatively described the composition of thrombi collected from the VA-ECMO circuits. We observed that these thrombi are mainly made of VWF, fibrin and in a lesser proportion of platelets and RBCs. Our quantitative approach also allowed us to demonstrate the presence of NETs while there was no active septic, confirming the possibility of aseptic NETosis under VA-ECMO. By hierarchical cluster analysis, we identified 2 types of thrombi, each of which may be related to a different mechanism of formation. In this study, the location of thrombi on the VA-ECMO circuit did not impact their compositions, highlighting the heterogeneity of thrombi formed within VA-ECMO and the multifactorial mechanisms that support thrombosis in this setting. In a second study, we compared the performance of surface coatings on VA-ECMO circuits to reduce thrombinoformation and its clinical consequences. Two of the most used coatings in daily practice were compared: the phosphorylcholin-based coating and the polysaccharide-albumin-based coating. We observed a higher rate of thrombotic complications in the phosphorylcholin group without any excess bleeding events or mortality in either group. In addition, compared with thrombi from phosphorylcholin-coated circuit junctions, those from polysaccharide-albumin-coated circuits were poorer in VWF. Our work suggests that the level of anticoagulation should be modulated according to the type of coating of the ECMO circuit.The aim of our third study was to identify the most relevant bleeding events that may guide clinical decision-making for more aggressive clinical management and a greater investment in research. To this end, we compared the association between 3 bleeding classifications with 28-day mortality. The ELSO definition already in use and the BARC classification classes ≥ type 2 were associated with 28-day mortality and thus retained as definitions of major bleeding. Laboratory parameters that are predictors major bleeding according to the ELSO definition were decreased fibrinogen, platelet count, and hemoglobin at cannulations. Body mass index and postcardiotomy etiology were also predictive of ELSO major bleeding. In an additional work related to the topic of the thesis, we studied two of the most used laboratory tests for the monitoring of systemic heparin during VA-ECMO, the APTT and the Anti-Xa activity, to identify the most relevant. First, we studied the relationship between these two tests and then analyzed in a second objective the impact of biological influencing factors on this relationship. Next, we determined their associations with thrombotic and hemorrhagic complications. Although linearly associated, the rate of discordance between their measurements was 39 % for an Anti-Xa reference range of 0.3 - 0.7 IU/mL. Neither APTT nor Anti-Xa was associated with thrombotic or bleeding complications. Taken together, our results highlight the heterogeneity of thrombi from peripheral VA-ECMO, the involvement of numerous causal factors that underline thrombotic and hemorrhagic complications, both not predictable by routine tests. Finally, our work underscored the need for new approaches in thrombotic or hemorrhagic complications management with targets set at an individual level considering both patient and ECMO circuit characteristics.La problématique de cette thèse est la caractérisation des complications liées à l’hémostase chez le patient assisté par ECMO-VA périphérique afin d’en améliorer la prévention et de rationaliser les approches antithrombotiques en usage. Dans une première étude, nous avons décrit qualitativement et quantitativement la composition des thrombi formés sur les circuits d’ECMO-VA. Nous avons observé que ces thrombi sont majoritairement composés de VWF, de fibrine et dans une moindre proportion de plaquettes et d’érythrocytes. Notre approche quantitative a également permis de mettre en évidence la présence de NETs en l’absence de toute pathologie septique active, confirmant la possibilité d’une NETose aseptique sous ECMO-VA. Par une analyse en cluster hiérarchique, nous avons identifié 2 types de thrombi pouvant relever chacun d’un mécanisme de formation différent. Dans cette étude, la localisation des thrombi sur le circuit d’ECMO-VA n’impactait pas leurs compositions, ce qui souligne l’hétérogénéité des thrombi formés sous ECMO-VA et la multiplicité des mécanismes à l’origine de la thrombinoformation dans ce contexte. Dans un second travail, nous avons comparé la performance des revêtements de surfaces des circuits d’ECMO-VA à réduire la thrombinoforation et ses conséquences cliniques. Deux des revêtements les plus utilisés en routine étaient comparés : celle à base de phosphorylcholine et à base d’héparine. Nous avons observé un taux de complications thrombotiques plus conséquent dans le groupe phosphorylcholine sans surrisque hémorragique ou de mortalité dans les deux groupes. Par ailleurs, comparativement aux thrombi issus des jonctions de circuits traités par revêtement de phosphorylcholine, ceux provenant de circuits traités par polysaccharide-albumine étaient plus pauvres en VWF. Notre travail suggère que l’intensité de l’anticoagulation devrait être modulée en fonction du type de revêtement de surface du circuit d’ECMO. Notre troisième étude avait pour but d’identifier les saignements les plus graves justifiants d’une prise en charge clinique agressive et d’un investissement plus conséquent en recherche. À cette fin, nous avons comparé l’association entre 3 classifications de saignement avec la mortalité à 28 jours. La définition ELSO déjà en usage et les classes de la classification BARC ≥ type 2 étaient associées à la mortalité et retenues donc comme définitions de l’hémorragie majeure. Les facteurs biologiques prédictifs de l’hémorragie grave d’après la définition de l’ELSO étaient la baisse du fibrinogène, du compte plaquettaire et de l’hémoglobine à la canulation. L’indice de masse corporelle et l’étiologie postcardiotomie étaient également prédictifs de la survenue de cette complication. Dans un travail additionnel portant sur la thématique de la thèse, nous avons étudié deux des tests les plus utilisés pour la surveillance de l’héparinothérapie systémique sous ECMO, le TCA et l’activité Anti-Xa afin d’identifier le plus pertinent. Pour ce faire, dans un premier objectif nous avons étudié la relation entre ces deux tests puis avons analysé dans un second objectif l’impact de facteurs biologiques d’influences sur cette relation. Ensuite, nous avons déterminé leurs associations avec les complications thrombotiques et hémorragiques. Bien qu’étant linéairement associé, le taux de discordance entre leurs mesures était de 39 % pour une fenêtre référence d’Anti-Xa de 0,3 — 0,7 UI/mL. Ni le TCA et ni l’Anti-Xa n’étaient associées aux complications thrombotiques ou hémorragiques [...

Déterminants cliniques, physiopathologiques et pronostics associés aux complications liées à l’hémostase au cours des assistances circulatoires de courte durée à pompe centrifuge

The purpose of this dissertation is to characterize hemostasis-related complications in patients supported by peripheral VA-ECMO to improve their prevention and to optimize the antithrombotic therapeutic approaches in use. In a first study, we qualitatively and quantitatively described the composition of thrombi collected from the VA-ECMO circuits. We observed that these thrombi are mainly made of VWF, fibrin and in a lesser proportion of platelets and RBCs. Our quantitative approach also allowed us to demonstrate the presence of NETs while there was no active septic, confirming the possibility of aseptic NETosis under VA-ECMO. By hierarchical cluster analysis, we identified 2 types of thrombi, each of which may be related to a different mechanism of formation. In this study, the location of thrombi on the VA-ECMO circuit did not impact their compositions, highlighting the heterogeneity of thrombi formed within VA-ECMO and the multifactorial mechanisms that support thrombosis in this setting. In a second study, we compared the performance of surface coatings on VA-ECMO circuits to reduce thrombinoformation and its clinical consequences. Two of the most used coatings in daily practice were compared: the phosphorylcholin-based coating and the polysaccharide-albumin-based coating. We observed a higher rate of thrombotic complications in the phosphorylcholin group without any excess bleeding events or mortality in either group. In addition, compared with thrombi from phosphorylcholin-coated circuit junctions, those from polysaccharide-albumin-coated circuits were poorer in VWF. Our work suggests that the level of anticoagulation should be modulated according to the type of coating of the ECMO circuit.The aim of our third study was to identify the most relevant bleeding events that may guide clinical decision-making for more aggressive clinical management and a greater investment in research. To this end, we compared the association between 3 bleeding classifications with 28-day mortality. The ELSO definition already in use and the BARC classification classes ≥ type 2 were associated with 28-day mortality and thus retained as definitions of major bleeding. Laboratory parameters that are predictors major bleeding according to the ELSO definition were decreased fibrinogen, platelet count, and hemoglobin at cannulations. Body mass index and postcardiotomy etiology were also predictive of ELSO major bleeding. In an additional work related to the topic of the thesis, we studied two of the most used laboratory tests for the monitoring of systemic heparin during VA-ECMO, the APTT and the Anti-Xa activity, to identify the most relevant. First, we studied the relationship between these two tests and then analyzed in a second objective the impact of biological influencing factors on this relationship. Next, we determined their associations with thrombotic and hemorrhagic complications. Although linearly associated, the rate of discordance between their measurements was 39 % for an Anti-Xa reference range of 0.3 - 0.7 IU/mL. Neither APTT nor Anti-Xa was associated with thrombotic or bleeding complications. Taken together, our results highlight the heterogeneity of thrombi from peripheral VA-ECMO, the involvement of numerous causal factors that underline thrombotic and hemorrhagic complications, both not predictable by routine tests. Finally, our work underscored the need for new approaches in thrombotic or hemorrhagic complications management with targets set at an individual level considering both patient and ECMO circuit characteristics.La problématique de cette thèse est la caractérisation des complications liées à l’hémostase chez le patient assisté par ECMO-VA périphérique afin d’en améliorer la prévention et de rationaliser les approches antithrombotiques en usage. Dans une première étude, nous avons décrit qualitativement et quantitativement la composition des thrombi formés sur les circuits d’ECMO-VA. Nous avons observé que ces thrombi sont majoritairement composés de VWF, de fibrine et dans une moindre proportion de plaquettes et d’érythrocytes. Notre approche quantitative a également permis de mettre en évidence la présence de NETs en l’absence de toute pathologie septique active, confirmant la possibilité d’une NETose aseptique sous ECMO-VA. Par une analyse en cluster hiérarchique, nous avons identifié 2 types de thrombi pouvant relever chacun d’un mécanisme de formation différent. Dans cette étude, la localisation des thrombi sur le circuit d’ECMO-VA n’impactait pas leurs compositions, ce qui souligne l’hétérogénéité des thrombi formés sous ECMO-VA et la multiplicité des mécanismes à l’origine de la thrombinoformation dans ce contexte. Dans un second travail, nous avons comparé la performance des revêtements de surfaces des circuits d’ECMO-VA à réduire la thrombinoforation et ses conséquences cliniques. Deux des revêtements les plus utilisés en routine étaient comparés : celle à base de phosphorylcholine et à base d’héparine. Nous avons observé un taux de complications thrombotiques plus conséquent dans le groupe phosphorylcholine sans surrisque hémorragique ou de mortalité dans les deux groupes. Par ailleurs, comparativement aux thrombi issus des jonctions de circuits traités par revêtement de phosphorylcholine, ceux provenant de circuits traités par polysaccharide-albumine étaient plus pauvres en VWF. Notre travail suggère que l’intensité de l’anticoagulation devrait être modulée en fonction du type de revêtement de surface du circuit d’ECMO. Notre troisième étude avait pour but d’identifier les saignements les plus graves justifiants d’une prise en charge clinique agressive et d’un investissement plus conséquent en recherche. À cette fin, nous avons comparé l’association entre 3 classifications de saignement avec la mortalité à 28 jours. La définition ELSO déjà en usage et les classes de la classification BARC ≥ type 2 étaient associées à la mortalité et retenues donc comme définitions de l’hémorragie majeure. Les facteurs biologiques prédictifs de l’hémorragie grave d’après la définition de l’ELSO étaient la baisse du fibrinogène, du compte plaquettaire et de l’hémoglobine à la canulation. L’indice de masse corporelle et l’étiologie postcardiotomie étaient également prédictifs de la survenue de cette complication. Dans un travail additionnel portant sur la thématique de la thèse, nous avons étudié deux des tests les plus utilisés pour la surveillance de l’héparinothérapie systémique sous ECMO, le TCA et l’activité Anti-Xa afin d’identifier le plus pertinent. Pour ce faire, dans un premier objectif nous avons étudié la relation entre ces deux tests puis avons analysé dans un second objectif l’impact de facteurs biologiques d’influences sur cette relation. Ensuite, nous avons déterminé leurs associations avec les complications thrombotiques et hémorragiques. Bien qu’étant linéairement associé, le taux de discordance entre leurs mesures était de 39 % pour une fenêtre référence d’Anti-Xa de 0,3 — 0,7 UI/mL. Ni le TCA et ni l’Anti-Xa n’étaient associées aux complications thrombotiques ou hémorragiques [...

Comparing habitat preferences of a set of waterbird species wintering in coastal wetlands of North Africa: implication for management

Every year, the Coastal wetlands of North Africa support an important wintering waterbird population of many Palearctic and sub-Saharan species of various contrasting habitat requirements. In this study, we describe the habitat use by24 water-obligate species wintering in a coastal wetland of the Northeastern Algeria (the wetland of Lake Tonga), highlighting thereby the ecological mechanisms that support their coexistence and their resources partitioning. The analysis of resource exploitation (Relative frequency, Feinsinger niche breadth, Pianka niche overlap and Ivlev’s electivity indexes) showed that waterbird species inhabiting the lake wetland have several similarities in using the different habitat categories, which lead us to cluster them into 5 guilds (G1: one rails, two grebes and eight ducks; G2: five wading species and one gull; G3: three herons; G4: cormorants, mallards, and on gull; finally, G5: only one species Cattle egret (Bubulcus ibis).Almost all the species were specialists in resource utilization patterns (narrow niche breadths, both under 0.3) and therefore, vulnerable to fluctuations in resources, particularly the feeding habitats. Mean niche overlaps for all the pairs of species ranged from 0.05 to 0.68. The overall pattern in the community was higher niche overlaps between the species of a particular guild than those between other species. According to Ivlev’s electivity index, we found that only three microhabitats from seven were the most important for the discussed species, open water body was the most attractive, followed by meadows, muddy areas and floating- leafed vegetation. Similarities on habitat requirements derived from our region can provide important and optimal wetland management at multi-species assemblage level for this wetland and similar area around the African coast

Recurrent symptomatic ischemic stroke in a 46-year-old African male revealing Angio-Behçet with severe cardiovascular involvement

Behçet’sdisease (BD) is a chronic, multisystem vasculitis. It is categorized under variable vessel vasculitis in the new Chapel Hill nomenclature as it involves blood vessels of any type and size. It is characterized by relapsing aphthous ulcers commonly occurring in the oral mucosa and genitalia with ocular involvement. Other organ systems may be involved any time throughout the course of the disease. The exact cause is unknown. However, combination of genetic and environmental factors is likely to play a role. Cardiac involvement may occur in the form of intracardiac thrombus, endocarditis, myocarditis, pericarditis, endomyocardial fibrosis, coronary arteritis, myocardial infarction, and valvular disease. We present a case of Angio-Behçet in a 46-year-old African male with severe cardiovascular involvement including pulmonary artery hypertension (PAH), right ventricular failure and left ventricular diastolic dysfunction diagnosed after 2 episodes of symptomatic ischemic stroke resulting from complete occlusion of the right internal carotid artery (ICA) up to its intracranial portion. Immunosuppressive and anticoagulant therapies have induced improvement in cardiac manifestations. Nevertheless, prompt recognition of the primarily vascular manifestation of BD without mucocutaneous manifestations was responsible for considerable delay that did not afford surgical therapy for the carotid occlusion

Mixed organic and bentonite based amendments improve soil hydrological conditions and irrigation efficiency in oasis soils

The major constraint for sustainable agriculture in arid regions of the world is the availability of (suitable irrigation) water. The quantity and quality of irrigation water, as well as the application technique and intervals between irrigation are important due to the useful amount of water brought to the soil and their direct influence on crop production. The oasis systems in southern Tunisia also suffer from scarcity of irrigation water resources because of low precipitation and limited available ground water. Organic matter (OM) application to improve soil fertility and enhance water holding capacity (WHC) is the traditional method in Tunisian oasis systems, but because of regional climatic conditions (dry and hot weather) the degradation of applied OM in the soils is very fast and consequently the WHC decreases too. The objective of this study was to examine the WHC of new alternative soil amendments in the oasis systems in a state of degradation. The soil studied is a gypsum soil. We compared these sandy soils amended either with (i) manure (MS), (ii) compost (CS), (iii) manure and bentonite (MBS) and (iv) compost and bentonite (CBS). The treatments were compared with untreated original oasis sandy soil (U). These five treatments were compared with the most degraded regional soil, i.e. that of the salt plain Chott Djerid (CD). To estimate the soil hydraulic parameters (including WHC) retention curves were measured and van Genuchten parameters fitted to the data. The results of soil water retention curves revealed that the untreated soil (U) retained less water at any matric potential compared to the amended soils. The soil hydraulic conductivity decreased with the use of bentonite combined with organic matter. The saturated hydraulic conductivity for untreated soil was higher than the amended soil with CBS and MBS by 11 and 18 times, respectively. These results suggested that the soil amendments significantly improved the soil water retention. Therefore these soil mixed amendments are appropriate for their potential wider use in sandy (oasis) soils to improve irrigation efficiency amounts and to reduce irrigation frequency

C53 - Revue Annuelle Produit : du Gardénal 50mg De Winthrop Pharma Sénégal / Groupe Sanofi

Introduction. La revue annuelle de la qualité des produits (RAQP), exigence internationale pour les formes finies et les substances actives, est particulièrement scrutée lors d’inspections et d’audits. Elle s'apparente à une validation rétrospective continue permettant de détecter toute dérive et de s’assurer de la fiabilité des procédés et de la qualité des produits. La RAQP du Gardénal 50mg (Phénobarbital) fabrique sur le site de Dakar en boite de 30 comprimes a porté sur cinq (5) lots Matériels et méthodes. L’évaluation des OOS/OOT a suivi la procédure CQ PRO 015. Les fiches de déclaration des résultats hors tendance ou non conformes obtenus lors de l’analyse au laboratoire, la description et la cause d’anomalie, le numéro de la déviation correspondante et de suivi des plans d’actions correctives et préventives (CAPA) ont été renseignées. Résultats. Les rendements, de 82,22-88,05%, étaient inférieurs à 98%. L’évaluation du poids moyen a montré des résultats conformes : 86.695-88.245 mg, pour une valeur cible de 87.500 mg. Les temps de désagrégation étaient conformes (60-637 sec), en dessous de la limite maximale de 900 sec. Il en a été de même pour le titre en Phénobarbital avec des résultats conformes de 47,80-50,80 mg/cp (moyenne 49,21 mg/cp). Deux déviations impactant deux lots ont été notées, respectivement, sur le dosage en principe actif pour le lot 2, le temps de désagrégation in process et le test de dissolution pour le lot 3 occasionnant son rejet après retraitement. Le lot 2 a fait l’objet d’une fiche OOT. Discussion. Quatre lots ont été libérés dans les 19 à 50 jours suivants leur fabrication. Huit actions correctives et préventives ont été clôturées à 100 % dans les délais. Seul le lot 3 a été rejeté après retraitement, suite à une dissolution non conforme 61% (limite 75%). Aucun lot n’a fait l’objet de réclamation, de rappel ou de retour. L’étude permet d’affirmer que le produit détient les qualités attribuées : l’évaluation du dosage en principe actif, des paramètres critiques in process, des paramètres de libération disponibles a donné des résultats conformes. Le process de fabrication a été validé