Haemodilution-induced profibrinolytic state is mitigated by fresh-frozen plasma: implications for early haemostatic intervention in massive haemorrhage

Background Fibrinolysis contributes to coagulopathy after major trauma and surgery. We hypothesized that progressive haemodilution is responsible, at least in part, for increased fibrinolytic tendency of blood clot. Methods The study was performed in two parts. First, whole blood (WB) samples collected from six healthy, consented volunteers were diluted in vitro with either saline or fresh-frozen plasma (FFP) to 40% and 15% of baseline. We quantified factor levels related to coagulation and fibrinolysis, and measured endogenous thrombin generation in undiluted control plasma samples and in samples diluted with saline or FFP. Additionally, thromboelastometry was used to assess susceptibility to fibrinolysis after adding tissue plasminogen activator in undiluted WB samples and in samples diluted with saline before and after substitution of fibrinogen or FFP. Secondly, as a model of in vivo haemodilution, we evaluated the same parameters before and after operation in nine consented patients undergoing off-pump coronary artery bypass surgery. Results The dilution with saline caused dose-dependent decreases in plasma levels of coagulation and antifibrinolytic factors, and in thrombin generation. In FFP-supplemented samples, factor levels and thrombin generation were maintained within normal ranges. Fibrinolytic tendency was significantly higher after haemodilution with saline independent of fibrinogen substitution compared with FFP. Similarly, increased tendency for fibrinolysis was also observed in the in vivo haemodilution. Conclusions We demonstrated in vitro and in vivo that progressive haemodilution decreases endogenous antifibrinolytic proteins including α2-antiplasmin and thrombin-activatable fibrinolysis inhibitor, resulting in increased fibrinolytic tendency. Therefore, early fluid replacement therapy with FFP might be advantageous after massive haemorrhag

Multiclass Semi-Supervised Learning on Graphs using Ginzburg-Landau Functional Minimization

We present a graph-based variational algorithm for classification of high-dimensional data, generalizing the binary diffuse interface model to the case of multiple classes. Motivated by total variation techniques, the method involves minimizing an energy functional made up of three terms. The first two terms promote a stepwise continuous classification function with sharp transitions between classes, while preserving symmetry among the class labels. The third term is a data fidelity term, allowing us to incorporate prior information into the model in a semi-supervised framework. The performance of the algorithm on synthetic data, as well as on the COIL and MNIST benchmark datasets, is competitive with state-of-the-art graph-based multiclass segmentation methods.Comment: 16 pages, to appear in Springer's Lecture Notes in Computer Science volume "Pattern Recognition Applications and Methods 2013", part of series on Advances in Intelligent and Soft Computin

Target Detection Performance Bounds in Compressive Imaging

This paper describes computationally efficient approaches and associated theoretical performance guarantees for the detection of known targets and anomalies from few projection measurements of the underlying signals. The proposed approaches accommodate signals of different strengths contaminated by a colored Gaussian background, and perform detection without reconstructing the underlying signals from the observations. The theoretical performance bounds of the target detector highlight fundamental tradeoffs among the number of measurements collected, amount of background signal present, signal-to-noise ratio, and similarity among potential targets coming from a known dictionary. The anomaly detector is designed to control the number of false discoveries. The proposed approach does not depend on a known sparse representation of targets; rather, the theoretical performance bounds exploit the structure of a known dictionary of targets and the distance preservation property of the measurement matrix. Simulation experiments illustrate the practicality and effectiveness of the proposed approaches.Comment: Submitted to the EURASIP Journal on Advances in Signal Processin

Differential Contributions of Intrinsic and Extrinsic Pathways to Thrombin Generation in Adult, Maternal and Cord Plasma Samples.

BACKGROUND:Thrombin generation (TG) is a pivotal process in achieving hemostasis. Coagulation profiles during pregnancy and early neonatal period are different from that of normal (non-pregnant) adults. In this ex vivo study, the differences in TG in maternal and cord plasma relative to normal adult plasma were studied. METHODS:Twenty consented pregnant women and ten consented healthy adults were included in the study. Maternal and cord blood samples were collected at the time of delivery. Platelet-poor plasma was isolated for the measurement of TG. In some samples, anti-FIXa aptamer, RB006, or a TFPI inhibitor, BAX499 were added to elucidate the contribution of intrinsic and extrinsic pathway to TG. Additionally, procoagulant and inhibitor levels were measured in maternal and cord plasma, and these values were used to mathematically simulate TG. RESULTS:Peak TG was increased in maternal plasma (393.6±57.9 nM) compared to adult and cord samples (323.2±38.9 nM and 209.9±29.5 nM, respectively). Inhibitory effects of RB006 on TG were less robust in maternal or cord plasma (52% vs. 12% respectively) than in adult plasma (81%). Likewise the effectiveness of BAX499 as represented by the increase in peak TG was much greater in adult (21%) than in maternal (10%) or cord plasma (12%). Further, BAX499 was more effective in reversing RB006 in adult plasma than in maternal or cord plasma. Ex vivo data were reproducible with the results of the mathematical simulation of TG. CONCLUSION:Normal parturient plasma shows a large intrinsic pathway reserve for TG compared to adult and cord plasma, while TG in cord plasma is sustained by extrinsic pathway, and low levels of TFPI and AT

Anti-factor IXa Aptamer reduces propagation of thrombin generation in plasma anticoagulated with warfarin

Warfarin is routinely used in the prevention and treatment of prothrombotic events. During initiation of warfarin therapy levels of factor (F) VII and protein C decrease rapidly but prothrombin, FIX and FX decline much slower. Therefore, propagation of thrombin generation (TG) remains unaffected much longer, increasing the risk of inadequate anticoagulation. Recently, a novel agent, anti-IXa aptamer, RB006, has been developed. Therefore, we have evaluated the in vitro effects of this agent in warfarin plasma

Differential Contributions of Intrinsic and Extrinsic Pathways to Thrombin Generation in Adult, Maternal and Cord Plasma Samples

<div><p>Background</p><p>Thrombin generation (TG) is a pivotal process in achieving hemostasis. Coagulation profiles during pregnancy and early neonatal period are different from that of normal (non-pregnant) adults. In this <i>ex vivo</i> study, the differences in TG in maternal and cord plasma relative to normal adult plasma were studied.</p><p>Methods</p><p>Twenty consented pregnant women and ten consented healthy adults were included in the study. Maternal and cord blood samples were collected at the time of delivery. Platelet-poor plasma was isolated for the measurement of TG. In some samples, anti-FIXa aptamer, RB006, or a TFPI inhibitor, BAX499 were added to elucidate the contribution of intrinsic and extrinsic pathway to TG. Additionally, procoagulant and inhibitor levels were measured in maternal and cord plasma, and these values were used to mathematically simulate TG.</p><p>Results</p><p>Peak TG was increased in maternal plasma (393.6±57.9 nM) compared to adult and cord samples (323.2±38.9 nM and 209.9±29.5 nM, respectively). Inhibitory effects of RB006 on TG were less robust in maternal or cord plasma (52% <i>vs</i>. 12% respectively) than in adult plasma (81%). Likewise the effectiveness of BAX499 as represented by the increase in peak TG was much greater in adult (21%) than in maternal (10%) or cord plasma (12%). Further, BAX499 was more effective in reversing RB006 in adult plasma than in maternal or cord plasma. <i>Ex vivo</i> data were reproducible with the results of the mathematical simulation of TG.</p><p>Conclusion</p><p>Normal parturient plasma shows a large intrinsic pathway reserve for TG compared to adult and cord plasma, while TG in cord plasma is sustained by extrinsic pathway, and low levels of TFPI and AT.</p></div

The Folk Song as a Source of Inspiration in Activities in Music Lessons in Primary Schools

Teachers often use folk songs as a means to teach children singing in tune and other musical skills or music theory. However, a deeper knowledge of the song itself happens to be missing. Yet, learning more about the music, looking deeper into its core can open new possibilities of its use in the classroom. The aim of this work is to demonstrate the path that a teacher should go through when, trying to gather knowledge about a folk song. Folk music is no more as popular as it used to be. It is therefore necessary for the teacher to spend more energy on the preparation to make it more attractive for the students. Folk song has the important feature of flexibility. The end of the 20lh century brought a new style of music combining folk songs with pop music. Its authors find inspiration in folklore, making it the basis of their own creative work. Such music thus reveals another possibility to bring the folk song closer to the today's audience and especially the young generation. Nevertheless, for the practical part I have chosen a different strategy: through encountering the folk music (songs of the southern Bohemia in this case) children learn about some features of modern pop music (from jazz through mid stream pop song to pop music. Powered by TCPDF (www.tcpdf.org

Effects of anti-FIXa (RB006) and anti-TFPI (BAX499) alone or in combination on thrombin generation parameters.

<p>Effects of anti-FIXa (RB006) and anti-TFPI (BAX499) alone or in combination on thrombin generation parameters.</p

Maternal and cord coagulation factors and inhibitors.

<p>Adult levels set at 100% are shown for comparison. Maternal and cord values expressed as mean ± standard deviation (SD).</p