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  1. Article ; Online: A general modeling framework for quantitative tracking, accurate prediction of ICU, and assessing vaccination for COVID-19 in Chile

    Patricio Cumsille / Oscar Rojas-Díaz / Carlos Conca

    Frontiers in Public Health, Vol

    2023  Volume 11

    Abstract: BackgroundOne of the main lessons of the COVID-19 pandemic is that we must prepare to face another pandemic like it. Consequently, this article aims to develop a general framework consisting of epidemiological modeling and a practical identifiability ... ...

    Abstract BackgroundOne of the main lessons of the COVID-19 pandemic is that we must prepare to face another pandemic like it. Consequently, this article aims to develop a general framework consisting of epidemiological modeling and a practical identifiability approach to assess combined vaccination and non-pharmaceutical intervention (NPI) strategies for the dynamics of any transmissible disease.Materials and methodsEpidemiological modeling of the present work relies on delay differential equations describing time variation and transitions between suitable compartments. The practical identifiability approach relies on parameter optimization, a parametric bootstrap technique, and data processing. We implemented a careful parameter optimization algorithm by searching for suitable initialization according to each processed dataset. In addition, we implemented a parametric bootstrap technique to accurately predict the ICU curve trend in the medium term and assess vaccination.ResultsWe show the framework's calibration capabilities for several processed COVID-19 datasets of different regions of Chile. We found a unique range of parameters that works well for every dataset and provides overall numerical stability and convergence for parameter optimization. Consequently, the framework produces outstanding results concerning quantitative tracking of COVID-19 dynamics. In addition, it allows us to accurately predict the ICU curve trend in the medium term and assess vaccination. Finally, it is reproducible since we provide open-source codes that consider parameter initialization standardized for every dataset.ConclusionThis work attempts to implement a holistic and general modeling framework for quantitative tracking of the dynamics of any transmissible disease, focusing on accurately predicting the ICU curve trend in the medium term and assessing vaccination. The scientific community could adapt it to evaluate the impact of combined vaccination and NPIs strategies for COVID-19 or any transmissible disease in any country and help ...
    Keywords COVID-19 ; predictive modeling ; epidemiological modeling ; time delays ; vaccination ; practical identifiability ; Public aspects of medicine ; RA1-1270
    Subject code 006
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: A Novel Synthetic Model of the Glucose-Insulin System for Patient-Wise Inference of Physiological Parameters From Small-Size OGTT Data

    Sebastián Contreras / David Medina-Ortiz / Carlos Conca / Álvaro Olivera-Nappa

    Frontiers in Bioengineering and Biotechnology, Vol

    2020  Volume 8

    Abstract: Existing mathematical models for the glucose-insulin (G-I) dynamics often involve variables that are not susceptible to direct measurement. Standard clinical tests for measuring G-I levels for diagnosing potential diseases are simple and relatively cheap, ...

    Abstract Existing mathematical models for the glucose-insulin (G-I) dynamics often involve variables that are not susceptible to direct measurement. Standard clinical tests for measuring G-I levels for diagnosing potential diseases are simple and relatively cheap, but seldom give enough information to allow the identification of model parameters within the range in which they have a biological meaning, thus generating a gap between mathematical modeling and any possible physiological explanation or clinical interpretation. In the present work, we present a synthetic mathematical model to represent the G-I dynamics in an Oral Glucose Tolerance Test (OGTT), which involves for the first time for OGTT-related models, Delay Differential Equations. Our model can represent the radically different behaviors observed in a studied cohort of 407 normoglycemic patients (the largest analyzed so far in parameter fitting experiments), all masked under the current threshold-based normality criteria. We also propose a novel approach to solve the parameter fitting inverse problem, involving the clustering of different G-I profiles, a simulation-based exploration of the feasible set, and the construction of an information function which reshapes it, based on the clinical records, experimental uncertainties, and physiological criteria. This method allowed an individual-wise recognition of the parameters of our model using small size OGTT data (5 measurements) directly, without modifying the routine procedures or requiring particular clinical setups. Therefore, our methodology can be easily applied to gain parametric insights to complement the existing tools for the diagnosis of G-I dysregulations. We tested the parameter stability and sensitivity for individual subjects, and an empirical relationship between such indexes and curve shapes was spotted. Since different G-I profiles, under the light of our model, are related to different physiological mechanisms, the present method offers a tool for personally-oriented diagnosis and treatment ...
    Keywords mathematical modeling ; glucose-insulin control ; OGTT ; inverse problems ; personalized medicine ; Biotechnology ; TP248.13-248.65
    Subject code 006
    Language English
    Publishing date 2020-03-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Patient-Wise Methodology to Assess Glycemic Health Status

    Álvaro Olivera-Nappa / Sebastian Contreras / María Florencia Tevy / David Medina-Ortiz / Andrés Leschot / Pilar Vigil / Carlos Conca

    Frontiers in Nutrition, Vol

    Applications to Quantify the Efficacy and Physiological Targets of Polyphenols on Glycemic Control

    2022  Volume 9

    Abstract: A growing body of evidence indicates that dietary polyphenols could be used as an early intervention to treat glucose-insulin (G-I) dysregulation. However, studies report heterogeneous information, and the targets of the intervention remain largely ... ...

    Abstract A growing body of evidence indicates that dietary polyphenols could be used as an early intervention to treat glucose-insulin (G-I) dysregulation. However, studies report heterogeneous information, and the targets of the intervention remain largely elusive. In this work, we provide a general methodology to quantify the effects of any given polyphenol-rich food or formulae over glycemic regulation in a patient-wise manner using an Oral Glucose Tolerance Test (OGTT). We use a mathematical model to represent individual OGTT curves as the coordinated action of subsystems, each one described by a parameter with physiological interpretation. Using the parameter values calculated for a cohort of 1198 individuals, we propose a statistical model to calculate the risk of dysglycemia and the coordination among subsystems for each subject, thus providing a continuous and individual health assessment. This method allows identifying individuals at high risk of dysglycemia—which would have been missed with traditional binary diagnostic methods—enabling early nutritional intervention with a polyphenol-supplemented diet where it is most effective and desirable. Besides, the proposed methodology assesses the effectiveness of interventions over time when applied to the OGTT curves of a treated individual. We illustrate the use of this method in a case study to assess the dose-dependent effects of Delphinol® on reducing dysglycemia risk and improving the coordination between subsystems. Finally, this strategy enables, on the one hand, the use of low-cost, non-invasive methods in population-scale nutritional studies. On the other hand, it will help practitioners assess the effectiveness of an intervention based on individual vulnerabilities and adapt the treatment to manage dysglycemia and avoid its progression into disease.
    Keywords dysglycemia risk ; glycemia ; precision preventive medicine ; early disglycemia diagnosis ; delphinol polyphenols ; quantitative diagnostic ; Nutrition. Foods and food supply ; TX341-641
    Subject code 360
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Parameter estimation and mathematical modeling for the quantitative description of therapy failure due to drug resistance in gastrointestinal stromal tumor metastasis to the liver.

    Patricio Cumsille / Matías Godoy / Ziomara P Gerdtzen / Carlos Conca

    PLoS ONE, Vol 14, Iss 5, p e

    2019  Volume 0217332

    Abstract: In this work we develop a general mathematical model and devise a practical identifiability approach for gastrointestinal stromal tumor (GIST) metastasis to the liver, with the aim of quantitatively describing therapy failure due to drug resistance. To ... ...

    Abstract In this work we develop a general mathematical model and devise a practical identifiability approach for gastrointestinal stromal tumor (GIST) metastasis to the liver, with the aim of quantitatively describing therapy failure due to drug resistance. To this end, we have modeled metastatic growth and therapy failure produced by resistance to two standard treatments based on tyrosine kinase inhibitors (Imatinib and Sunitinib) that have been observed clinically in patients with GIST metastasis to the liver. The parameter identification problem is difficult to solve, since there are no general results on this issue for models based on ordinary differential equations (ODE) like the ones studied here. We propose a general modeling framework based on ODE for GIST metastatic growth and therapy failure due to drug resistance and analyzed five different model variants, using medical image observations (CT scans) from patients that exhibit drug resistance. The associated parameter estimation problem was solved using the Nelder-Mead simplex algorithm, by adding a regularization term to the objective function to address model instability, and assessing the agreement of either an absolute or proportional error in the objective function. We compared the goodness of fit to data for the proposed model variants, as well as evaluated both error forms in order to improve parameter estimation results. From the model variants analyzed, we identified the one that provides the best fit to all the available patient data sets, as well as the best assumption in computing the objective function (absolute or proportional error). This is the first work that reports mathematical models capable of capturing and quantitatively describing therapy failure due to drug resistance based on clinical images in a patient-specific manner.
    Keywords Medicine ; R ; Science ; Q
    Subject code 310
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: A systems biology approach for studying Wolbachia metabolism reveals points of interaction with its host in the context of arboviral infection.

    Natalia E Jiménez / Ziomara P Gerdtzen / Álvaro Olivera-Nappa / J Cristian Salgado / Carlos Conca

    PLoS Neglected Tropical Diseases, Vol 13, Iss 8, p e

    2019  Volume 0007678

    Abstract: Wolbachia are alpha-proteobacteria known to infect arthropods, which are of interest for disease control since they have been associated with improved resistance to viral infection. Although several genomes for different strains have been sequenced, ... ...

    Abstract Wolbachia are alpha-proteobacteria known to infect arthropods, which are of interest for disease control since they have been associated with improved resistance to viral infection. Although several genomes for different strains have been sequenced, there is little knowledge regarding the relationship between this bacterium and their hosts, particularly on their dependency for survival. Motivated by the potential applications on disease control, we developed genome-scale models of four Wolbachia strains known to infect arthropods: wAlbB (Aedes albopictus), wVitA (Nasonia vitripennis), wMel and wMelPop (Drosophila melanogaster). The obtained metabolic reconstructions exhibit a metabolism relying mainly on amino acids for energy production and biomass synthesis. A gap analysis was performed to detect metabolic candidates which could explain the endosymbiotic nature of this bacterium, finding that amino acids, requirements for ubiquinone precursors and provisioning of metabolites such as riboflavin could play a crucial role in this relationship. This work provides a systems biology perspective for studying the relationship of Wolbachia with its host and the development of new approaches for control of the spread of arboviral diseases. This approach, where metabolic gaps are key objects of study instead of just additions to complete a model, could be applied to other endosymbiotic bacteria of interest.
    Keywords Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
    Subject code 570
    Language English
    Publishing date 2019-08-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: A semilinear control problem involving homogenization

    Carlos Conca / Axel Osses / Jeannine Saint Jean Paulin

    Electronic Journal of Differential Equations, Vol Conference, Iss 06, Pp 109-

    2001  Volume 122

    Abstract: We consider a control problem involving a semilinear elliptic equation with a uniformly Lipschitz non-linearity and rapidly oscillating coefficients in a bounded domain of $mathbb{R}^N$. The control is distributed on a compact subset interior to the ... ...

    Abstract We consider a control problem involving a semilinear elliptic equation with a uniformly Lipschitz non-linearity and rapidly oscillating coefficients in a bounded domain of $mathbb{R}^N$. The control is distributed on a compact subset interior to the domain. Given an $N-1$ dimensional hypersurface at the interior of the domain not intersecting the control zone, the trace of the solution on the curve has to be controlled. We prove that there exists a limit control as the homogenization parameter converges to zero, which results as the limit of fixed points for controllability problems. We link this limit control with the corresponding homogenized problem.
    Keywords control ; homogenization ; semilinear elliptic equation. ; Mathematics ; QA1-939 ; Science ; Q ; DOAJ:Mathematics ; DOAJ:Mathematics and Statistics
    Language English
    Publishing date 2001-01-01T00:00:00Z
    Publisher Texas State University
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Homogenization in chemical reactive flows

    Carlos Conca / Jesus Ildefonso Diaz / Amable Linan / Claudia Timofte

    Electronic Journal of Differential Equations, Vol 2004, Iss 40, Pp 1-

    2004  Volume 22

    Abstract: This paper concerns the homogenization of two nonlinear models for chemical reactive flows through the exterior of a domain containing periodically distributed reactive solid grains (or reactive obstacles). In the first model, the chemical reactions take ...

    Abstract This paper concerns the homogenization of two nonlinear models for chemical reactive flows through the exterior of a domain containing periodically distributed reactive solid grains (or reactive obstacles). In the first model, the chemical reactions take place on the walls of the grains, while in the second one the fluid penetrates the grains and the reactions take place therein. The effective behavior of these reactive flows is described by a new elliptic boundary-value problem containing an extra zero-order term which captures the effect of the chemical reactions.
    Keywords Homogenization ; reactive flows ; variational inequality ; monotone graph. ; Mathematics ; QA1-939 ; Science ; Q ; DOAJ:Mathematics ; DOAJ:Mathematics and Statistics
    Language English
    Publishing date 2004-03-01T00:00:00Z
    Publisher Texas State University
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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