1,721,454 research outputs found
The iterative two-stage population approach to IVGTT minimal modeling: improved precision with reduced sampling. Intravenous glucose tolerance test
No full textThe minimal model method is widely used to estimate glucose effectiveness (S(G)) and insulin sensitivity (S(I)) from intravenous glucose tolerance test (IVGTT) data. In the standard protocol (sIVGTT, 0.33 g/kg glucose bolus given at time 0), which allows the simultaneous assessment of beta-cell function, the precision of the individualized estimates often degrades and particularly so in the presence of reduced sampling schedules. Here, we investigated the use of a population approach, the iterative two-stage (ITS) approach, to analyze 16 sIVGTTs in healthy subjects and to obtain refined estimates of S(G) and S(I) in the population and in the individual subjects. The ITS is based on calculation of the population mean and standard deviation of the parameters at each iteration and then use of them as prior information for the individual analyses. Theoretically, the use of a prior in the ITS should improve the precision of the individual estimates. The customary approach (standard two stage, STS), where modeling is performed separately for each individual subject, does not take the population knowledge into account. We used both frequent (FSS, 30 samples) and (quasi-optimally) reduced (RSS, 14 samples) sampling schedules. For the FSS, STS gave estimates (mean +/- SD) for S(G) = 2.66 +/- 1.09 x 10(-2). min(-1) and S(I) = 6.46 +/- 6.99 10(-4). min(-1). microU(-1). ml, with an average precision of 51 (range 5-176) and 33% (3-91), respectively. RSS radically worsened the precision of both S(G) and S(I). However, RSS and ITS gave S(G) = 2.59 +/- 0.73 and S(I) = 6.06 +/- 7.28, with an average precision of 23 (12-42) and 27% (), respectively. In conclusion, population minimal modeling of sIVGTT data improves the precision of individual estimates of glucose effectiveness and insulin sensitivity, as the theory predicts, and, even with reduced sampling, the improvement is substantial
Parameter estimation in distributed models of blood-tissue exchange: a Monte Carlo strategy to assess precision of parameter estimates
No full textistributed parameter models of blood-tissue exchange are increasingly used to interpret multiple tracer dilution data in regional kinetic studies. To derive a measure of the precision with which the model parameters are estimated is therefore of paramount importance. The standard approach to deriving precision of estimates does not take into account the fact that some of the model parameters are fixed. Thus, the precision of parameter estimates is not realistic and, in all likelihood, it is overestimated. The aim of this study is to describe a Monte Carlo method devised to obtain a theoretically sound measure of the precision of estimates, which takes into account both measurement error and the uncertainty associated with the fixed parameters. The fixed parameter values are taken from a probability distribution. By letting the fixed parameters vary according to their distribution, a large number of synthetic datasets is generated. Noise is then added. Estimating the parameters in each of these synthetic datasets allows the derivation of a Monte Carlo mean and standard deviation, which provides a realistic measure of precision. The methodology is illustrated for a simulated data case study dealing with the estimation of the capillary permeability-surface area product in a two tracer experiment
A priori identifiability of distributed models of blood-tissue exchange
No full textA priori identifiability deals with the uniqueness of the solution for the unknown parameters of a dynamic model from a given input-output experiment, and is a prerequisite for well posedness of parameter estimation from the data. Identifiability has been extensively investigated for lumped parameter, linear, and nonlinear dynamic models, in particular, compartmental models of biological systems. Much less attention has been devoted to distributed parameter model, in particular, those describing blood-tissue exchange, which are normally used to interpret regional multiple tracer dilution experiments. In this paper, we study a priori identifiability of distributed parameter models of transcapillary exchange, focusing first on a single capillary (one-region) model, then moving on to a single capillary-interstitial fluid (two-region) model, and finally to an organ model also describing flow heterogeneity
Cellular signaling identifiability analysis: a case study. Journal of Theoretical Biology, vol.264, 528-537, 2010.
No full textTwo primary purposes for mathematical modeling in cell biology are (1) simulation for making predictions of experimental outcomes and (2) parameter estimation for drawing inferences from experimental data about unobserved aspects of biological systems. While the former purpose has become common in the biological sciences, the latter is less common, particularly when studying cellular and subcellular phenomena such as signaling—the focus of the current study. Data are difficult to obtain at this level. Therefore, even models of only modest complexity can contain parameters for which the available data are insufficient for estimation. In the present study, we use a set of published cellular signaling models to address issues related to global parameter identifiability. That is, we address the following question: assuming known time courses for some model variables, which parameters is it theoretically impossible to estimate, even with continuous, noise-free data? Following an introduction to this problem and its relevance, we perform a full identifiability analysis on a set of cellular signaling models using DAISY (Differential Algebra for the Identifiability of SYstems). We use our analysis to bring to light important issues related to parameter identifiability in ordinary differential equation (ODE) models. We contend that this is, as of yet, an under-appreciated issue in biological modeling and, more particularly, cell biology
The hot IVGTT two compartment minimal model: indices of glucose effectiveness and insulin sensitivity.
No full textA two-compartment minimal model (2CMM) has been proposed [A. Caumo and C. Cobelli. Am. J. Physiol. 264 (Endocrinol. Metab. 27): E829-E841, 1993] to describe intravenous glucose tolerance test (IVGTT) labeled (hereafter hot) glucose kinetics. This model, at variance with the one-compartment minimal model (1CMM), allows the estimation of a plausible profile of glucose production. The aim of this study is to show that the 2CMM also allows the assessment of insulin sensitivity (SI2*), glucose effectiveness (SG2*), and plasma clearance rate (PCR). The 2CMM was identified on stable-isotope IVGTTs performed in normal subjects (n = 14). Results were (means +/- SE) SG2* = 0.85 +/- 0.14 ml.kg-1.min-1, PCR = 2.02 +/- 0.14 ml.kg-1.min-1, and SI2* = 13.83 +/- 2.54 x 10(-2) ml.kg-1.min-1.microU-1.ml. The 1CMM was also identified; glucose effectiveness and insulin sensitivity indexes were SG*V = 1.36 +/- 0.08 ml.kg-1.min-1 and SI*V = 12.98 +/- 2.21 x 10(-2) ml.kg-1.min-1.microU-1.ml, respectively, where V is the 1CMM glucose distribution volume. SG*V was lower than PCR and higher than SG2* and did not correlate with either [r = 0.45 (NS) and r = 0.50 (NS), respectively], whereas SI*V was not different from and was correlated with SI2* (r = 0.95; P < 0.001). SG* compares well (r = 0.78; P < 0.001) with PCR normalized by the 2CMM total glucose distribution volume. In conclusion, the 2CMM is a powerful tool to assess glucose metabolism in vivo
Comparison of insulin sensitivity and glucose effectiveness determined by the one- and two-compartment-labeled minimal model in late prepubertal children and early adolescents
No full textMultiple methods are used to determine insulin sensitivity. Most commonly used in children are euglycemic-hyperinsulinemic clamp and frequently sampled intravenous glucose tolerance (FSIVGTT) with minimal modeling (MinMod). The parameters S(G) and S(I) of MinMod are related to insulin sensitivity and glucose effectiveness, respectively, but inappropriate modeling of glucose kinetics causes inaccuracies. Glucose tracer use may mitigate such inaccuracies, allowing use of multiple modeling approaches, including a 2-compartment model (2CMM). This study was designed to compare the 1-compartment model (1CMM) and 2CMM in a pediatric population. Twenty-three children were studied 4 times using FSIVGTT with [6,6] D(2) glucose. Glucose effectiveness and insulin sensitivity were calculated by 1CMM (S*(G1) and S*(I1)) and 2CMM (S*(G2) and S*(I2)). Indices were reliably estimated in 86 of 87 tests for 1CMM, but only in 49 for 2CMM. S*(G1) overestimated S*(G2), but they were positively related. S*(I1) and S*(12) were not different and were positively related. This suggests that inadequate modeling by the 1CMM has a smaller impact on glucose tolerance indices in children than in adults. Comparison with classical MinMod gave results analogous to those in adults (MinMod S(G) was larger than S*(G1), MinMod S(I) was smaller than S*(I1)). These results demonstrate significant differences in glucose effectiveness, but not insulin sensitivity, as measured by 1CMM and 2CMM in early adolescents. Thus, when insulin sensitivity is the primary interest, the 1CMM is more robust because its parameters are more reliably estimated than those of 2CMM and is the logical choice in pediatric population-based studies
Double isotope tracer method for measuring fractional zinc absorption: theoretical analysis
Full text linkSeveral approaches for estimation of fractional zinc absorption (FZA) by calculating the ratio of oral to intravenous stable isotopic tracer concentrations (at an appropriate time) in urine or plasma after their simultaneous administration have been proposed in the last decade. These simple-to-implement approaches, often referred to as the double isotopic tracer ratio (DITR) method, are more attractive than the classical "deconvolution" method and the more commonly used single-tracer methods based on fecal monitoring and indicator dilution, after oral or intravenous tracer administration, respectively. However, the domain of validity of DITR for measuring FZA has recently been questioned. In this paper, we provide a theoretical justification of the validity of four different "approximate" formulations of the DITR technique by demonstrating mathematically that their accuracy is a consequence of the particular properties of zinc kinetics
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Cemaat and the City: Muslim Reconstruction in Modern Turkey
No full textThis article examines the transformation of Islamic religious communities in Turkey since the 1950s, highlighting their adaptation to urbanization, secular education, and new organizational forms. It traces how traditional Sufi as well as other Sufi-inspired networks transition into more bureaucratic and service-oriented communities, known as cemaats, focusing on education, civic engagement, and the cultivation of Muslim awareness. The article explores how collective learning practices and mediatized religious discourse replace the role of charismatic masters, as groups like the Nur movement and the Gülen community emphasize text-based guidance over personal allegiance. It also analyzes how Naqshbandi groups navigate Turkey’s modernization processes by leveraging educational and media institutions to expand their influence in public life. The article concludes that while these transformations ensure Islam’s continued relevance in modern Turkey, they also reshape Muslim religious authority, fostering new forms of organization that differ significantly from their Ottoman and early Republican predecessors
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