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Search Results: 1 - 10 of 147019 matches for " Claus F Larsen "
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Thrombelastography and biomarker profiles in acute coagulopathy of trauma: a prospective study
Sisse R Ostrowski, Anne S?rensen, Claus F Larsen, P?r I Johansson
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine , 2011, DOI: 10.1186/1757-7241-19-64
Abstract: Prospective observational study of 80 trauma patients admitted to a Level I Trauma Centre. Data on demography, biochemistry including standard coagulation tests, hematology, transfusions, Injury Severity Score (ISS) and TEG were recorded. Retrospective analysis of thawed plasma/serum for biomarkers reflecting tissue injury (histone-complexed DNA fragments), sympathoadrenal activation (adrenaline, noradrenaline), coagulation activation/inhibition and fibrinolysis (sCD40L, protein C, activated Protein C, tissue-type plasminogen activator, plasminogen activator inhibitor-1, D-dimer, prothrombinfragment 1+2, plasmin/α2-antiplasmin complex, thrombin/antithrombin complex, tissue factor pathway inhibitor, antithrombin, von willebrand factor, factor XIII). Comparison of patients stratified according to ISS/TEG maximum clot strength. Linear regression analysis of variables associated with clot strength.Trauma patients had normal (86%), hypercoagulable (11%) or hypocoagulable (1%) TEG clot strength; one had primary hyperfibrinolysis. Hypercoagulable patients had higher age, fibrinogen and platelet count (all p < 0.05), none had increased activated partial thromboplastin time (APTT) or international normalized ratio (INR) and none required massive transfusion (> 10 red blood cells the initial 24 h). Patients with normal or hypercoagulable TEG clot strength had comparable biomarker profiles, but the few patients with hypocoagulable TEG clot strength and/or hyperfibrinolysis had very different biomarker profiles.Increasing ISS was associated with higher levels of catecholamines, histone-complexed DNA fragments, sCD40L, activated protein C and D-dimer and reduced levels of non-activated protein C, antithrombin, fibrinogen and factor XIII (all p < 0.05). Fibrinogen and platelet count were associated independently with clot strength in patients with ISS ≤ 26 whereas only fibrinogen was associated independently with clot strength in patients with ISS > 26. In patients with ISS > 26,
Bioreversible Derivatives of Phenol. 1. The Role of Human Serum Albumin as Related to the Stability and Binding Properties of Carbonate Esters with Fatty Acid-like Structures in Aqueous Solution and Biological Media
Jesper Ostergaard,Claus Larsen
Molecules , 2007, DOI: 10.3390/12102380
Abstract: With the overall objective of assessing the potential of utilizing plasma protein binding interactions in combination with the prodrug approach for improving the pharmacokinetics of drug substances, a series of model carbonate ester prodrugs of phenol, encompassing derivatives with fatty acid-like structures, were characterized in vitro. Stability of the derivatives was studied in aqueous solution, human serum albumin solution, human plasma, and rat liver homogenate at 37°C. Stability of the derivatives in aqueous solution varied widely, with half-lives ranging from 31 to 1.7 × 104 min at pH 7.4 and 37°C. The carbonate esters were subject to catalysis by plasma esterases except for the t-butyl and acetic acid derivatives, which were stabilized in both human plasma and human serum albumin solutions relative to buffer. In most cases, however, hydrolysis was accelerated in the presence of human serum albumin indicating that the derivatives interacted with the protein, a finding which was confirmed using the p-nitrophenyl acetate kinetic assay. Different human serum albumin binding properties of the phenol model prodrugs with fatty acid-like structure and neutral carbonate esters were observed. In the context of utilizing plasma protein binding in combination with the prodrug approach for optimizing drug pharmacokinetics, the esterase-like properties of human serum albumin towards the carbonate esters potentially allowing the protein to act as a catalyst of parent compound regenerations is interesting.
Bioreversible Derivatives of Phenol. 2. Reactivity of Carbonate Esters with Fatty Acid-like Structures Towards Hydrolysis in Aqueous Solutions
Jesper Ostergaard,Claus Larsen
Molecules , 2007, DOI: 10.3390/12102396
Abstract: A series of model phenol carbonate ester prodrugs encompassing derivatives with fatty acid-like structures were synthesized and their stability as a function of pH (range 0.4 – 12.5) at 37°C in aqueous buffer solutions investigated. The hydrolysis rates in aqueous solutions differed widely, depending on the selected pro-moieties (alkyl and aryl substituents). The observed reactivity differences could be rationalized by the inductive and steric properties of the substituent groups when taking into account that the mechanism of hydrolysis may change when the type of pro-moiety is altered, e.g. n-alkyl vs. t-butyl. Hydrolysis of the phenolic carbonate ester 2-(phenoxycarbonyloxy)-acetic acid was increased due to intramolecular catalysis, as compared to the derivatives synthesized from ω-hydroxy carboxylic acids with longer alkyl chains. The carbonate esters appear to be less reactive towards specific acid and base catalyzed hydrolysis than phenyl acetate. The results underline that it is unrealistic to expect that phenolic carbonate ester prodrugs can be utilized in ready to use aqueous formulations. The stability of the carbonate ester derivatives with fatty acid-like structures, expected to interact with the plasma protein human serum albumin, proved sufficient for further in vitro and in vivo evaluation of the potential of utilizing HSA binding in combination with the prodrug approach for optimization of drug pharmacokinetics.
Disseminated intravascular coagulation or acute coagulopathy of trauma shock early after trauma? An observational study
P?r I Johansson, Anne S?rensen, Anders Perner, Karen Welling, Michael Wanscher, Claus F Larsen, Sisse R Ostrowski
Critical Care , 2011, DOI: 10.1186/cc10553
Abstract: An observational study was carried out at a single Level I Trauma Center. Eighty adult trauma patients (≥18 years) who met criteria for full trauma team activation and had an arterial cannula inserted were included. Blood was sampled a median of 68 minutes (IQR 48 to 88) post-injury. Data on demography, biochemistry, injury severity score (ISS) and mortality were recorded. Plasma/serum was analyzed for biomarkers reflecting tissue/endothelial cell/glycocalyx damage (histone-complexed DNA fragments, Annexin V, thrombomodulin, syndecan-1), coagulation activation/inhibition (prothrombinfragment 1+2, thrombin/antithrombin-complexes, antithrombin, protein C, activated protein C, endothelial protein C receptor, protein S, tissue factor pathway inhibitor, vWF), factor consumption (fibrinogen, FXIII), fibrinolysis (D-dimer, tissue-type plasminogen activator, plasminogen activator inhibitor-1) and inflammation (interleukin (IL)-6, terminal complement complex (sC5b-9)). Comparison of patients stratified according to the presence or absence of overt DIC (International Society of Thrombosis and Hemostasis (ISTH) criteria) or ACoTS (activated partial thromboplastin time (APTT) and/or international normalized ratio (INR) above normal reference).No patients had overt DIC whereas 15% had ACoTS. ACoTS patients had higher ISS, transfusion requirements and mortality (all P < 0.01) and a biomarker profile suggestive of enhanced tissue, endothelial cell and glycocalyx damage and consumption coagulopathy with low protein C, antithrombin, fibrinogen and FXIII levels, hyperfibrinolysis and inflammation (all P < 0.05). Importantly, in non-ACoTS patients, apart from APTT/INR, higher ISS correlated with biomarkers of enhanced tissue, endothelial cell and glycocalyx damage, protein C activation, coagulation factor consumption, hyperfibrinolysis and inflammation, that is, resembling that observed in patients with ACoTS.ACoTS and non-ACoTS may represent a continuum of coagulopathy reflecting a p
High levels of soluble VEGF receptor 1 early after trauma are associated with shock, sympathoadrenal activation, glycocalyx degradation and inflammation in severely injured patients: a prospective study
Sisse R Ostrowski, Anne Marie S?rensen, Nis A Windel?v, Anders Perner, Karen-Lise Welling, Michael Wanscher, Claus F Larsen, P?r I Johansson
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine , 2012, DOI: 10.1186/1757-7241-20-27
Abstract: Prospective observational study of 80 trauma patients admitted to a Level I Trauma Centre. Data on demography, biochemistry, Injury Severity Score (ISS), transfusions and 30-day mortality were recorded and plasma/serum (sampled a median of 68 min (IQR 48-88) post-injury) was analyzed for sVEGFR1 and biomarkers reflecting sympathoadrenal activation (adrenaline, noradrenaline), tissue injury (histone-complexed DNA fragments, hcDNA), endothelial activation and damage (von Willebrand Factor Antigen, Angiopoietin-2, soluble endothelial protein C receptor, syndecan-1, soluble thrombomodulin (sTM)), coagulation activation/inhibition and fibrinolysis (prothrombinfragment 1 + 2, protein C, activated Protein C, tissue-type plasminogen activator, plasminogen activator inhibitor-1, D-dimer) and inflammation (interleukin-6). Spearman correlations and regression analyses to identify variables associated with sVEGFR1 and its predictive value.Circulating sVEGFR1 correlated with injury severity (ISS, rho = 0.46), shock (SBE, rho = -0.38; adrenaline, rho = 0.47), tissue injury (hcDNA, rho = 0.44) and inflammation (IL-6, rho = 0.54) (all p < 0.01) but by multivariate linear regression analysis only lower SBE and higher adrenaline and IL-6 were independent predictors of higher sVEGFR1. sVEGFR1 also correlated with biomarkers indicative of endothelial glycocalyx degradation (syndecan-1, rho = 0.67), endothelial cell damage (sTM, rho = 0.66) and activation (Ang-2, rho = 0.31) and hyperfibrinolysis (tPA, rho = 0.39; D-dimer, rho = 0.58) and with activated protein C (rho = 0.31) (all p < 0.01). High circulating sVEGFR1 correlated with high early and late transfusion requirements (number of packed red blood cells (RBC) at 1 h (rho = 0.27, p = 0.016), 6 h (rho = 0.27, p = 0.017) and 24 h (rho = 0.31, p = 0.004) but was not associated with mortality.sVEGFR1 increased with increasing injury severity, shock and inflammation early after trauma but only sympathoadrenal activation, hypoperfusion,
Parameterized Metatheory for Continuous Markovian Logic
Kim G. Larsen,Radu Mardare,Claus Thrane
Electronic Proceedings in Theoretical Computer Science , 2012, DOI: 10.4204/eptcs.103.4
Abstract: This paper shows that a classic metalogical framework, including all Boolean operators, can be used to support the development of a metric behavioural theory for Markov processes. Previously, only intuitionistic frameworks or frameworks without negation and logical implication have been developed to fulfill this task. The focus of this paper is on continuous Markovian logic (CML), a logic that characterizes stochastic bisimulation of Markov processes with an arbitrary measurable state space and continuous-time transitions. For a parameter epsilon>0 interpreted as observational error, we introduce an epsilon-parameterized metatheory for CML: we define the concepts of epsilon-satisfiability and epsilon-provability related by a sound and complete axiomatization and prove a series of "parameterized" metatheorems including decidability, weak completeness and finite model property. We also prove results regarding the relations between metalogical concepts defined for different parameters. Using this framework, we can characterize both the stochastic bisimulation relation and various observational preorders based on behavioural pseudometrics. The main contribution of this paper is proving that all these analyses can actually be done using a unified complete Boolean framework. This extends the state of the art in this field, since the related works only propose intuitionistic contexts that limit, for instance, the use of the Boolean logical implication.
Distances for Weighted Transition Systems: Games and Properties
Uli Fahrenberg,Claus Thrane,Kim G. Larsen
Electronic Proceedings in Theoretical Computer Science , 2011, DOI: 10.4204/eptcs.57.10
Abstract: We develop a general framework for reasoning about distances between transition systems with quantitative information. Taking as starting point an arbitrary distance on system traces, we show how this leads to natural definitions of a linear and a branching distance on states of such a transition system. We show that our framework generalizes and unifies a large variety of previously considered system distances, and we develop some general properties of our distances. We also show that if the trace distance admits a recursive characterization, then the corresponding branching distance can be obtained as a least fixed point to a similar recursive characterization. The central tool in our work is a theory of infinite path-building games with quantitative objectives.
Near Horizon Geometry and Black Holes in Four Dimensions
V. Balasubramanian,F. Larsen
Physics , 1998, DOI: 10.1016/S0550-3213(98)00334-4
Abstract: A large class of extremal and near-extremal four dimensional black holes in M-theory feature near horizon geometries that contain three dimensional asymptotically anti-de Sitter spaces. Globally, these geometries are derived from AdS_3 by discrete identifications. The microstates of such black holes can be counted by exploiting the conformal symmetry induced on the anti-de Sitter boundary, and the result agrees with the Bekenstein-Hawking area law. This approach, pioneered by Strominger, clarifies the physical nature of the black hole microstates. It also suggests that recent analyses of the relationship between boundary conformal field theory and supergravity can be extended to orbifolds of AdS spaces.
Tailoring Properties of Biocompatible PEG-DMA Hydrogels with UV Light  [PDF]
Sania B?ckstr?m, Juana Benavente, Rolf W. Berg, Karin Stibius, Marianne S. Larsen, Henrik Bohr, Claus Hélix-Nielsen
Materials Sciences and Applications (MSA) , 2012, DOI: 10.4236/msa.2012.36060
Abstract: Hydrogels are highly water-absorbent hydrophilic polymer networks, which show potential in many biocompatible applications. In previous work, we demonstrated the feasibility of using poly(ethylene glycol) dimethacrylate (PEG-DMA) gels polymerized with a photoinitiator for encapsulation and stabilization of painted biomimetic membrane arrays for novel separation technologies or biosensor applications. These gels were formed from PEG-DMA monomers suspended in phosphate buffered saline (PBS) solution and gelated by radical polymerization in the presence of the photoinitiator Darocur 1173. In this work, we show that the properties of a PEG-DMA hydrogel formed by photoinitiated polymerizetion can be tailored by varying the photocrosslinking time. Fourier Transform Infrared Spectroscopy (FTIR) and Raman Spectroscopy (RS) showed that the optimal crosslinking time for the gel was 6 - 10 minutes and that the water content of the gels could be tuned in the range of 50 - 90 wt%. The resistivity was between 0.8 - 3.5 Ωm, which is comparable to that of PBS. The low resistivity of the gel makes it compatible for encapsulating membranes for (ion channel based) biosensor applications. With FTIR and RS we identified spectral features of the hydrogel, which may serve as a diagnostic tool to monitor changes in the gels due to variation in parameters such as time, pH, temperature, aging or exposure to chemicals or biological material.
Blood Profile of Proteins and Steroid Hormones Predicts Weight Change after Weight Loss with Interactions of Dietary Protein Level and Glycemic Index
Ping Wang,Claus Holst,Malene R. Andersen,Arne Astrup,Freek G. Bouwman,Sanne van Otterdijk,Will K. W. H. Wodzig,Marleen A. van Baak,Thomas M. Larsen,Susan A. Jebb,Anthony Kafatos,Andreas F. H. Pfeiffer,J. Alfredo Martinez,Teodora Handjieva-Darlenska,Marie Kunesova,Wim H. M. Saris,Edwin C. M. Mariman
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0016773
Abstract: Weight regain after weight loss is common. In the Diogenes dietary intervention study, high protein and low glycemic index (GI) diet improved weight maintenance.
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