Browsing by Author "Sarenac, Olivera (23971098200)"

Objectives: Copula is a tool for measuring linear and non-linear interactions between two or more time series. The aim of this paper is to prove that a copula approach can accurately capture and visualize the spatial and temporal fluctuations in dependency structures of cardiovascular signals, and to outline the application possibilities. Methods: The method for measuring the level of interaction between systolic blood pressure and the corresponding pulse interval is validated statistically and pharmacologically. The time series are recorded from the freely moving male Wistar rats equipped with radio-telemetry device for blood pressure recording, before and after administration of autonomic blockers scopolamine, atenolol, prazosin and hexamethonium. Implicit (Gaussian and t) and explicit (Clayton, Frank and Gumbel) copulas were calculated and compared to the conventional bivariate methods (Kendal, Pearson, Spearman and classical correlation). Further statistical validation was done using artificially generated surrogate data. A window sliding procedure for dynamic monitoring the signals’ coupling strength is implemented. Results: Under the baseline physiological conditions, SBP-PI dependency is significant for time lags 0 s–4 s. Hexamethonium completely abolished the dependency, scopolamine abolished it for time lags 0 s–2 s, atenolol first slightly increased, than for lags greater than 2 s decreased the dependency and prazosin had no effect. Isospectral and isodistributional surrogate data tests confirm that copulas successfully notify the absence of dependency as well. Conclusion: Copula approach accurately captures the temporal fluctuations in dependency structures of SBP and PI, simultaneously enabling a visualization of dependency levels within the particular signal zones. An analysis showed that copulas are more sensitive than the conventional statistical measures, with Frank copula exhibiting the best characterization of SBP and PI dependency. © 2018 The Authors

Objectives: Copula is a tool for measuring linear and non-linear interactions between two or more time series. The aim of this paper is to prove that a copula approach can accurately capture and visualize the spatial and temporal fluctuations in dependency structures of cardiovascular signals, and to outline the application possibilities. Methods: The method for measuring the level of interaction between systolic blood pressure and the corresponding pulse interval is validated statistically and pharmacologically. The time series are recorded from the freely moving male Wistar rats equipped with radio-telemetry device for blood pressure recording, before and after administration of autonomic blockers scopolamine, atenolol, prazosin and hexamethonium. Implicit (Gaussian and t) and explicit (Clayton, Frank and Gumbel) copulas were calculated and compared to the conventional bivariate methods (Kendal, Pearson, Spearman and classical correlation). Further statistical validation was done using artificially generated surrogate data. A window sliding procedure for dynamic monitoring the signals’ coupling strength is implemented. Results: Under the baseline physiological conditions, SBP-PI dependency is significant for time lags 0 s–4 s. Hexamethonium completely abolished the dependency, scopolamine abolished it for time lags 0 s–2 s, atenolol first slightly increased, than for lags greater than 2 s decreased the dependency and prazosin had no effect. Isospectral and isodistributional surrogate data tests confirm that copulas successfully notify the absence of dependency as well. Conclusion: Copula approach accurately captures the temporal fluctuations in dependency structures of SBP and PI, simultaneously enabling a visualization of dependency levels within the particular signal zones. An analysis showed that copulas are more sensitive than the conventional statistical measures, with Frank copula exhibiting the best characterization of SBP and PI dependency. © 2018 The Authors

Doxorubicin (DOX) is a chemotherapy medication used to treat cancer, but inducing deleterious cardiomyopathy resistant to treatment as an adverse effect. The present work aims to define phenotype/s of doxorubicin-induced cardiomyopathy in rats, firs manually, then using the automatic procedures. Male Wistar rats equipped with radio telemetry devices, were randomized in the DOX group (n=18) and control group (n=6). The variables collected included hemodynamic, echocardiography, blood analysis, patohistology, and histomorphometry. The visual arrangement of variables (a heat-map) was performed by hierarchical agglomerative clustering. A robust and reliable subject clustering was performed using the modified evidence accumulation algorithm that combines K-means++, affinity propagation, and Gaussian mixture model. The results point to at least two distinct phenotypes of DOX-induced cardiomyopathy: one with preserved and mid-range left ventricular ejection fraction (LVEF) and another with reduced LVEF. The automatic procedures a) point out the subject that should be manually rechecked and b) assist in finding the solutions for potential ambiguities. © 2020 IEEE.

Doxorubicin (DOX) is a chemotherapy medication used to treat cancer, but inducing deleterious cardiomyopathy resistant to treatment as an adverse effect. The present work aims to define phenotype/s of doxorubicin-induced cardiomyopathy in rats, firs manually, then using the automatic procedures. Male Wistar rats equipped with radio telemetry devices, were randomized in the DOX group (n=18) and control group (n=6). The variables collected included hemodynamic, echocardiography, blood analysis, patohistology, and histomorphometry. The visual arrangement of variables (a heat-map) was performed by hierarchical agglomerative clustering. A robust and reliable subject clustering was performed using the modified evidence accumulation algorithm that combines K-means++, affinity propagation, and Gaussian mixture model. The results point to at least two distinct phenotypes of DOX-induced cardiomyopathy: one with preserved and mid-range left ventricular ejection fraction (LVEF) and another with reduced LVEF. The automatic procedures a) point out the subject that should be manually rechecked and b) assist in finding the solutions for potential ambiguities. © 2020 IEEE.

Elderly people exhibit a diminished capacity to cope with osmotic challenges such as dehydration. We have undertaken a detailed molecular analysis of arginine vasopressin (AVP) biosynthetic processes in the supraoptic nucleus (SON) of the hypothalamus and secretory activity in the posterior pituitary of adult (3 months) and aged (18 months) rats, to provide a comprehensive analysis of age-associated changes to the AVP system. By matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, we identified differences in pituitary peptides, including AVP, in adult and aged rats under both basal and dehydrated states. In the SON, increased Avp gene transcription, coincided with reduced Avp promoter methylation in aged rats. Based on transcriptome data, we have previously characterized a number of novel dehydration-induced regulatory factors involved in the response of the SON to osmotic cues. We found that some of these increase in expression with age, while dehydration-induced expression of these genes in the SON was attenuated in aged rats. In summary, we show that aging alters the rat AVP system at the genome, transcriptome, and peptidome levels. These alterations however did not affect circulating levels of AVP in basal or dehydrated states. © 2018 The Authors

Elderly people exhibit a diminished capacity to cope with osmotic challenges such as dehydration. We have undertaken a detailed molecular analysis of arginine vasopressin (AVP) biosynthetic processes in the supraoptic nucleus (SON) of the hypothalamus and secretory activity in the posterior pituitary of adult (3 months) and aged (18 months) rats, to provide a comprehensive analysis of age-associated changes to the AVP system. By matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, we identified differences in pituitary peptides, including AVP, in adult and aged rats under both basal and dehydrated states. In the SON, increased Avp gene transcription, coincided with reduced Avp promoter methylation in aged rats. Based on transcriptome data, we have previously characterized a number of novel dehydration-induced regulatory factors involved in the response of the SON to osmotic cues. We found that some of these increase in expression with age, while dehydration-induced expression of these genes in the SON was attenuated in aged rats. In summary, we show that aging alters the rat AVP system at the genome, transcriptome, and peptidome levels. These alterations however did not affect circulating levels of AVP in basal or dehydrated states. © 2018 The Authors