Impaired endogenous fibrinolysis at high shear using a point-of-care test in STEMI is associated with alterations in clot architecture

© The Author(s) 2019Impaired endogenous fibrinolysis is an adverse prognostic biomarker in acute coronary syndrome (ACS). Abnormally dense in vitro fibrin thrombi have been demonstrated in ACS patients and related to hypofibrinolysis using cumbersome, laboratory-based methods. We aimed to assess endogenous fibrinolysis using a point-of-care technique and relate this to clot architecture. From patients with ST-segment elevation myocardial infarction (STEMI), venous blood was drawn immediately on arrival to assess thrombotic status. Blood was assessed using the point-of-care Global Thrombosis Test which measures occlusive thrombus formation under high shear and subsequently endogenous fibrinolysis (lysis time, LT). Two samples per patient were run in parallel. In one channel, the measurement was allowed to proceed as normal. In the other, after occlusion, thrombus was extracted, washed, fixed in glutaraldehyde, dried, sputter-coated, and assessed using scanning electron microscope. Endogenous fibrinolysis was strongly associated fibrin fibre thickness (p = 0.0001). As LT increased (less efficient fibrinolysis), the fibrin network of the thrombus was significantly more compact and dense, with thinner fibrin fibres and smaller gaps. Fibrin fibre thickness correlated inversely with LT (r = - 0.89, p = 0.001). Adverse clot architecture in vitro is directly related to impaired endogenous fibrinolysis using a relatively new point-of-care technique in patients with STEMI. This may transform the relevance of fibrin clot architecture from an off-line laboratory association to being directly relevant to endogenous fibrinolysis at the patient bedside, which could be used as a near-patient test to guide prognosis and assess the effect of treatment.Peer reviewedFinal Published versio

Real-Gas Effects and Phase Separation in Underexpanded Jets at Engine-Relevant Conditions

A numerical framework implemented in the open-source tool OpenFOAM is presented in this work combining a hybrid, pressure-based solver with a vapor-liquid equilibrium model based on the cubic equation of state. This framework is used in the present work to investigate underexpanded jets at engine-relevant conditions where real-gas effects and mixture induced phase separation are probable to occur. A thorough validation and discussion of the applied vapor-liquid equilibrium model is conducted by means of general thermodynamic relations and measurement data available in the literature. Engine-relevant simulation cases for two different fuels were defined. Analyses of the flow field show that the used fuel has a first order effect on the occurrence of phase separation. In the case of phase separation two different effects could be revealed causing the single-phase instability, namely the strong expansion and the mixing of the fuel with the chamber gas. A comparison of single-phase and two-phase jets disclosed that the phase separation leads to a completely different penetration depth in contrast to single-phase injection and therefore commonly used analytical approaches fail to predict the penetration depth.Comment: Preprint submitted to AIAA Scitech 2018, Kissimmee, Florid

A scientific methodology for researching CALL interaction data: Multimodal LEarning and TEaching Corpora

International audienceThis chapter gives an overview of one possible staged methodology for structuring LCI data by presenting a new scientific object, LEarning and TEaching Corpora (LETEC). Firstly, the chapter clarifies the notion of corpora, used in so many different ways in language studies, and underlines how corpora differ from raw language data. Secondly, using examples taken from actual online learning situations, the chapter illustrates the methodology that is used to collect, transform and organize data from online learning situations in order to make them sharable through open-access repositories. The ethics and rights for releasing a corpus as OpenData are discussed. Thirdly, the authors suggest how the transcription of interactions may become more systematic, and what benefits may be expected from analysis tools, before opening the CALL research perspective applied to LCI towards its applications to teacher-training in Computer-Mediated Communication (CMC), and the common interests the CALL field shares with researchers in the field of Corpus Linguistics working on CMC

Absence of Fas-L aggravates renal injury in acute Trypanosoma cruzi infection

Trypanosoma cruzi infection induces diverse alterations in immunocompetent cells and organs, myocarditis and congestive heart failure. However, the physiological network of disturbances imposed by the infection has not been addressed thoroughly. Regarding myocarditis induced by the infection, we observed in our previous work that Fas-L-/- mice (gld/gld) have very mild inflammatory infiltration when compared to BALB/c mice. However, all mice from both lineages die in the early acute phase. Therefore, in this work we studied the physiological connection relating arterial pressure, renal function/damage and cardiac insufficiency as causes of death. Our results show that a broader set of dysfunctions that could be classified as a cardio/anaemic/renal syndrome is more likely responsible for cardiac failure and death in both lineages. However, gld/gld mice had very early glomerular deposition of IgM and a more intense renal inflammatory response with reduced renal filtration, which is probably responsible for the premature death in the absence of significant myocarditis in gld/gld.Instituto Oswaldo Cruz-Fiocruz Laboratório de Biologia CelularUniversidade Federal do Rio de Janeiro Instituto de Biofísica Carlos Chagas FilhoUniversidade Federal Fluminense Instituto Biomédico Departamento de Fisiologia e FarmacologiaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Disciplina de NefrologiaCentro de Criação de Animais de Laboratório Departamento de Controle de Qualidade AnimalUNIFESP, EPM, Disciplina de NefrologiaSciEL

Systems biology of platelet-vessel wall interactions

Platelets are small, anucleated cells that participate in primary hemostasis by forming a hemostatic plug at the site of a blood vessel's breach, preventing blood loss. However, hemostatic events can lead to excessive thrombosis, resulting in life-threatening strokes, emboli, or infarction. Development of multi-scale models coupling processes at several scales and running predictive model simulations on powerful computer clusters can help interdisciplinary groups of researchers to suggest and test new patient-specific treatment strategies

Soluble urokinase receptor conjugated to carrier red blood cells binds latent pro-urokinase and alters its functional profile

Coupling plasminogen activators to carrier red blood cells (RBC) prolongs their life-time in the circulation and restricts extravascular side effects, thereby allowing their utility for short-term thromboprophylaxis. Unlike constitutively active plasminogen activators, single chain urokinase plasminogen activator (scuPA) is activated by plasmin proteolysis or binding to its receptor, uPAR. In this study we conjugated recombinant soluble uPAR (suPAR) to rat RBC, forming RBC/suPAR complex. RBC carrying suPAR circulated in rats similarly to naïve RBC and markedly prolonged the circulation time of suPAR. RBC/suPAR carrying ~ 3 × 104 suPAR molecules per RBC specifically bound up to 2 × 104 molecules of scuPA, retained ~ 75% of scuPA-binding capacity after circulation in rats and markedly altered the functional profile of bound scuPA. RBC carrying directly conjugated scuPA adhered to endothelial cells, while showing no appreciable fibrinolytic activity. In contrast, RBC/suPAR loaded with scuPA did not exhibit increased adhesion to endothelium, while effectively dissolving fibrin clots. This molecular design, capitalizing on unique biological features of the interaction of scuPA with its receptor, provides a promising modality to deliver a pro-drug for prevention of thrombosis

Mapping the interaction between uPAR and high molecular weight kininogen

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106070/1/jth03972.pd