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Your search keyword '"Brummel-Ziedins, Kathleen E."' showing total 75 results
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75 results on '"Brummel-Ziedins, Kathleen E."'

52. From Principle to Practice: Bridging the Gap in Patient Profiling

Author

Foley, Jonathan H., primary, Orfeo, Thomas, additional, Undas, Anetta, additional, McLean, Kelley C., additional, Bernstein, Ira M., additional, Rivard, Georges-Etienne, additional, Mann, Kenneth G., additional, Everse, Stephen J., additional, and Brummel-Ziedins, Kathleen E., additional

Published
2013
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73. The impact of uncertainty in a blood coagulation model.

Author

Danforth, Christopher M., Orfeo, Thomas, Mann, Kenneth G., Brummel-Ziedins, Kathleen E., and Everse, Stephen J.

Abstract

Deterministic mathematical models of biochemical processes operate as if the empirically derived rate constants governing the dynamics are known with certainty. Our objective in this study was to explore the sensitivity of a deterministic model of blood coagulation to variations in the values of its 44 rate constants. This was accomplished for each rate constant at a given time by defining a normalized ensemble standard deviation (wkif(t)) that accounted for the sensitivity of the predicted concentration of each protein species to variation in that rate constant (from 10 to 1000% of the accepted value). A mean coefficient of variation derived from (wkif(t)) values for all protein species was defined to quantify the overall variation introduced into the model's predictive capacity at that time by the assumed uncertainty in that rate constant. A time-average value of the coefficient of variation over the 20-min simulation for each rate constant was then used to rank rate constants. The model's predictive capacity is particularly sensitive (50% of the aggregate variation) to uncertainty in five rate constants involved in the regulation of the formation and function of the factor VIIa–tissue factor complex. Therefore, our analysis has identified specific rate constants to which the predictive capability of this model is most sensitive and thus where improvements in measurement accuracy will yield the greatest increase in predictive capability. [ABSTRACT FROM PUBLISHER]

Published
2009
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75. Antithrombotic properties of aspirin and resistance to aspirin: beyond strictly antiplatelet actions

Author

Undas, Anetta, Brummel-Ziedins, Kathleen E., and Mann, Kenneth G.

Abstract

Aspirin is effective in the prevention of cardiovascular events in high-risk patients. The primary established effect of aspirin on hemostasis is to impair platelet aggregation via inhibition of platelet thromboxane A2 synthesis, thus reducing thrombus formation on the surface of the damaged arterial wall. Growing evidence also indicates that aspirin exerts additional antithrombotic effects, which appear to some extent unrelated to platelet thromboxane A2 production. Aspirin can reduce thrombin generation with the subsequent attenuation of thrombin-mediated coagulant reactions such as factor XIII activation. Aspirin also acetylates lysine residues in fibrinogen resulting in increased fibrin clot permeability and enhanced clot lysis as well as directly promoting fibrinolysis with high-dose aspirin. The variable effectiveness of aspirin in terms of clinical outcomes and laboratory findings, which has been termed aspirin resistance, may be related to these additional antithrombotic effects that are altered when associated with common genetic polymorphisms such as the Leu33Pro β3-integrin or Val34Leu factor XIII mutations. However, the clinical relevance of these observations is still unclear. Elucidation of the actual impacts of aspirin other than antiaggregation effects could be important in view of the widespread use of this drug in the prevention of thrombotic manifestations of atherosclerosis.

Published
2007
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