A program to estimate insulin sensitivity and pancreatic responsivity from an IVGTT using the minimal modeling technique

A user-friendly program coded in PASCAL for the IBM PC has been developed to determine the etiology of impaired glucose tolerance using an intravenous glucose tolerance test (IVGTT). It makes use of the "minimal modeling technique," a method that has been shown to be adequate for the quantitative determination of insulin sensitivity and insulin resistance. Two models are used, the minimal model of glucose disappearance and the minimal model of insulin kinetics. The first model is described by two nonlinear ordinary differential equations (ODEs) which are solved numerically, and which yield the insulin sensitivity index SI. The second model is described by an ODE for which an explicit solution was obtained, and which yields the pancreatic responsivity parameters phi 1 and phi 2. The product SI.phi 2 can be used to segregate subjects into "good" and "low" tolerance types. The program provides best-fit plots along with numerical values of the parameters and their uncertainties, and requires little intervention from the user. The fact that it requires a noninvasive IVGTT as input and that it has been written for the ubiquitous IBM PC are added advantages.     

Insulin sensitivity in type 2 diabetes: univariate and multivariate techniques to derive estimates of insulin sensitivity from the insulin modified intravenous glucose tolerance test (FSIGT)

The use of univariate and multivariate techniques to derive estimates of insulin sensitivity from the insulin modified FSIGT were investigated in 12 Type 2 diabetic subjects aged (mean+/-S.D.) 59+/-9.5 years and BMI 28.1+/-2.2 kg m(-2), who underwent both a FSIGT and an isoglycemic hyperinsulinemic clamp. Reproducibility of the FSIGT was tested in four patients on three separate occasions. FSIGT data were assessed by both univariate and multivariate techniques. The sensitivity index for the FSIGT ranged from 0.162 to 3.292 (mean 1.378) x 10(-4) x l min(-1) mU(-1) for the univariate approach and from 0.163 to 2.727 (mean 1.378) x 10(-4) x l min(-1) mU(-1) for the multivariate method. Mean S(Iclamp) was 44.41 x 10(-4) x l(-2) min(-1) x mU(-1) (range 22.0-77.92). The correlation of the insulin sensitivity indices between the clamp and the FSIGT was 0.51 (P=0.056) for the univariate and 0.67 (P=0.017) for the multivariate analyses. Repeated FSIGTs showed a lower variability for the multivariate than for the standard approach.     

ISEC: a program to calculate insulin secretion

ISEC (Insulin SECretion) is a computer program which calculates pre-hepatic insulin secretion from plasma C-peptide measurements. The program uses a regression (population) model to derive parameters of C-peptide kinetics from subject's gender, type (normal, obese, non-insulin dependent diabetes mellitus), age, weight, and height. Insulin secretion is calculated as a piece-wise constant (step) function with flexible step length allowing for a fine resolution of the secretion profile between measurements. A constrained regularisation method of deconvolution is employed to carry out the calculations. The calculated profile satisfies three properties: (i) it fits the measurement within the given level of the measurement error, (ii) it is non-negative, and (iii) it has a minimum value of a regularisation criterion (norm of second differences) which quantifies the degree of deviation of the secretion profile from a straight line. Both theoretical aspects and specific features related to ISEC are considered. To exemplify the use of ISEC, pre-hepatic insulin secretion is calculated during meal tolerance test, frequently sampled intravenous glucose tolerance test, hyperinsulinaemic euglycaemic glucose clamp, and basal conditions with frequent sampling.     

Model-based assessment of insulin sensitivity of glucose disposal and endogenous glucose production from double-tracer oral glucose tolerance test

A new mathematical model of short-term glucose regulation by insulin is proposed to exploit the oral glucose tolerance test (OGTT), which is commonly used for clinical diagnosis of glucose intolerance and diabetes. Contributions of endogenous and exogenous sources to measured plasma glucose concentrations have been separated by means of additional oral administration and constant intravenous infusion of glucose labeled with two different tracers. Twelve type 2 diabetic patients (7 males and 5 females) and 10 control subjects (5 males and 5 females) with normal glucose tolerance and matched body mass index (BMI) participated in this study. Blood samples for measurement of concentrations/activity of unlabeled and double-tracer glucose and insulin were collected every 15 min for 3 h following the oral glucose load. A minimal model combined with non-linear mixed-effects population parameter estimation has been devised to characterize group-average and between-patient variability of: (i) gastrointestinal glucose absorption; (ii) endogenous glucose production (EGP), and (iii) glucose disposal rate. Results indicate that insulin-independent glucose clearance does not vary significantly with gender or diabetic state and that the latter strongly affects, as expected, insulin-dependent clearance (insulin sensitivity). Inhibition of EGP, interpreted in terms of variations from basal of insulin concentrations, does not appear to be affected by diabetes but rather by BMI, i.e. by the degree of obesity. This study supports the utility of a minimal modelling approach, combined with population parameter estimation, to characterize glucose absorption, production and disposition during double-tracer OGTT experiments. The model provides a means for planning further experiments to validate the new hypothesis on the influence of individual factors, such as BMI and diabetes, on glucose appearance and disappearance, and for designing new simplified clinical tests.     

WTRBLN: a computer program to calculate water balance

Program WTRBLN calculates water balance based on the basis of long-term average monthly precipitation, potential evapotranspiration, and combined soil and vegetation characteristics, according to the method proposed by Thornthwaite and Mather. Three additions to the original method are implemented: (1) direct runoff can be taken into account, (2) reference potential evapotranspiration can be adjusted to crop potential evapotranspiration by Kc factors, and (3) a successive approximation method can be selected by user if the area climate is so dry that the soil never reaches field capacity.     

Application of the SAAM modeling program to minimal model analysis of intravenous glucose tolerance test data

The minimal model approach to analysis of intravenous glucose tolerance tests (IVGTT) yields estimates of parameters representing insulin sensitivity, glucose-mediated glucose disposal and pancreatic responsiveness. The precision of these estimates can deteriorate if the glucose and insulin data lack well-defined structure or freedom from data noise (random error). The precision of parameter estimates can be enhanced if data sets from two or more IVGTTs, obtained under different experimental conditions in the same subject, are analysed together in one data file. Following initial fitting using CONSAM, the conversational version of the modeling program SAAM, those parameters whose estimates remain at the same value under the different experimental conditions are constrained. This effectively reduces the number of adjustable parameters, and their estimates can then be fine-tuned with enhanced precision using the batch version of SAAM.     

BUFMAKE: a computer program to calculate the compositions of buffers of defined buffer capacity and ionic strength for ultra-violet spectrophotometry

A versatile computer program, BUFMAKE, was developed to calculate the composition of buffer solution for a given pH value with the ability to optimize the buffer capacity and ionic strength. The software was exemplified using a five-component buffer recipe which consists of boric acid, citric acid, ethylenediamine, potassium dihydrogen orthophosphate and trishydroxymethylaminomethane. It has been demonstrated that the proposed buffer solution with the composition calculated by the BUFMAKE program is suitable for use in ultra-violet spectrophotometry over a broad range of pH (2–12), buffer capacity (0.01–0.05) and ionic strength (0.1–0.3).     

Modal: a program to calculate compositions of ternary systems within the qz-or-ab-an tetrahedron from modal-analysis data

Program MODAL transforms raw point-count data into volume and weight-percent values. By using the An-content of plagioclase and the Ab-content of alkali feldspar it reduces the percentages of the petrogenetically important feldspars to the pure components and calculates the four faces of the Qz-Or-Ab-An tetrahedron for volume-, weight- and molepercent. The program provides a routine for plotting triangular diagrams on the line printer as well as on the CALCOMP plotter. It also is possible to have the projections of points on the cotectic line plotted into the triangular diagrams.The results can be used for petrogenetic discussions and can be directly compared with other (e.g. normative) data and experimentally determined phase relationships within the granite/granodiorite system.     

Modified minimal model using a single-step fitting process for the intravenous glucose tolerance test in Type 2 diabetes and healthy humans

The classical minimal model with single compartment was modified by the assumption that the insulin decay rate is not always a first-order process, and a mathematical function for describing the insulin infusion rate is introduced. The modified model was used to study four sets of published data including healthy humans and Type 2 diabetes with different types of insulin infusion rates. The single-step fitting process took the glucose-insulin system as a dynamic integrated physiological system and generated the real optimized model parameters from the experimental data using the modified model. It also avoided the errors from the interpolation or extrapolation for taking measured insulin points as inputs, which were mostly employed in publications when using the single or multi-compartments minimal model. The averaged R(2) value between measured and calculated plasma concentrations for these four cases is 0.977, which indicates excellent agreement.     

POTENCOR: a program to calculate power and correlation spectra of EEG signals

This work describes a computer program (POTENCOR) that applying the Fast Fourier Transform and Pearson product-moment correlation, can calculate easily, fast and accurately the absolute and relative power as well as the inter- and intrahemispheric correlation between every pair of EEG signals for narrow bands and for broad bands. POTENCOR has three main advantages: (1) it allows calculation of inter- and intrahemispheric correlation spectra, for which to our knowledge, there is no commercial program available; (2) the absolute and relative power values are not affected by the number of points that constitutes the signal segment; and (3) in case of making the analysis by each segment the temporal evolution for each EEG parameter can be graphically represented. The utility and flexibility of this program has been confirmed in many clinical and experimental researches.     

Extension of Fisher's exact test to 2-by-k contingency tables: a computer program in BASIC

A randomisation method of analysis for 2 X k contingency table data has been developed. This method, which is based on the fundamental principle of Fisher's exact probability test, gives a more accurate evaluation of the significance probability than does the chi-square test, especially when the sample size is small. A listing from the computer program in BASIC to carry out the 'exact probability test' for analysis of 2 X k contingency table data is available from the authors.     

micrOMEGAs 2.0.7: a program to calculate the relic density of dark matter in a generic model

micrOMEGAs2.0.7 is a code which calculates the relic density of a stable massive particle in an arbitrary model. The underlying assumption is that there is a conservation law like R-parity in supersymmetry which guarantees the stability of the lightest odd particle. The new physics model must be incorporated in the notation of CalcHEP, a package for the automatic generation of squared matrix elements. Once this is done, all annihilation and coannihilation channels are included automatically in any model. Cross-sections at v=0, relevant for indirect detection of dark matter, are also computed automatically. The package includes three sample models: the minimal supersymmetric standard model (MSSM), the MSSM with complex phases and the NMSSM. Extension to other models, including non supersymmetric models, is described.

Program summary

Title of program:micrOMEGAs2.0.7Catalogue identifier:ADQR_v2_1Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADQR_v2_1.htmlProgram obtainable from: CPC Program Library, Queen's University of Belfast, N. IrelandLicensing provisions:Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.htmlNo. of lines in distributed program, including test data, etc.:216 529No. of bytes in distributed program, including test data, etc.:1 848 816Distribution format:tar.gzProgramming language used:C and FortranComputer:PC, Alpha, Mac, SunOperating system:UNIX (Linux, OSF1, SunOS, Darwin, Cygwin)RAM:17 MB depending on the number of processes requiredClassification:1.9, 11.6Catalogue identifier of previous version:ADQR_v2_0Journal version of previous version:Comput. Phys. Comm. 176 (2007) 367Does the new version supersede the previous version?:YesNature of problem:Calculation of the relic density of the lightest stable particle in a generic new model of particle physics.Solution method:In numerically solving the evolution equation for the density of dark matter, relativistic formulae for the thermal average are used. All tree-level processes for annihilation and coannihilation of new particles in the model are included. The cross-sections for all processes are calculated exactly with CalcHEP after definition of a model file. Higher-order QCD corrections to Higgs couplings to quark pairs are included.Reasons for new version:The main changes in this new version consist, on the one hand, in improvements of the user interface and treatment of error codes when using spectrum calculators in the MSSM and, on the other hand, on a completely revised code for the calculation of the relic density in the NMSSM based on the code NMSSMTools1.0.2 for the computation of the spectrum.Summary of revisions:

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The version of CalcHEP was updated to CalcHEP 2.4.

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The procedure for shared library generation has been improved. Now the libraries are recalculated each time the model is modified.

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The default value for the top quark mass has been set to 171.4 GeV.

Changes specific to the MSSM model.

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The deltaMb correction is now included in the B,t,H-vertex and is always included for other Higgs vertices.

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In case of a fatal error in an RGE program, micrOMEGAs now continues operation while issuing a warning that the given point is not valid. This is important when running scans over parameter space. However this means that the standard ˆC command that could be used to cancel a job now only cancels the RGE program. To cancel a job, use “kill -9 -N” where N is the micrOMEGAs process id, all child processes launched by micrOMEGAs will be killed at once.

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Following the last SLHA2 release, we use key=26 item of EXTPAR block for the pole mass of the CP-odd Higgs so that micrOMEGAs can now use SoftSUSY for spectrum calculation with EWSB input. The Isajet interface was corrected too, so the user has to recompile the isajet_slha executable. For SuSpect we still support an old “wrong” interface where key=24 is used for the mass of the CP-odd Higgs.

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In the non-universal SUGRA model, we set the value of M₀ (M1/2,A₀) to the value of the largest subset of equal parameters among scalar masses (gaugino masses, trilinear couplings). In the previous version these parameters were set arbitrarily to be equal to MH2, MG2 and At respectively. The spectrum calculators need an input value for M₀,M1/2 and A₀ for initialisation purposes.

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We have removed bugs in micrOMEGAs-Isajet interface in case of non-universal SUGRA.

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$(FFLAGS) is added to compilation instruction of suspect.exe. It was omitted in version 2.0.

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The treatment of errors in reading of the LesHouches accord file is improved. Now, if the SPINFO block is absent in the SLHA output it is considered as a fatal error.

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Instructions for calculation of Δρ, μ(g−2), Br(b→sγ) and Br(Bs→μ⁺μ⁻) constraints are included in EWSB sample main programs omg.c/omg.cpp/omg.F.

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We have corrected the name of the library for neutralino-neutralino annihilation in our sample files MSSM/cs br.*.

Changes specific to the NMSSM model.

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The NMSSM has been completely revised. Now it is based on NMSSMTools_1.0.2.

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The deltaMb corrections in the NMSSM are included in the Higgs potential.

CP violation model.

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We have included in our package the MSSM with CP violation. Our implementation was described in Phys. Rev. D 73 (2006) 115007. It is based on the CPSUPERH package published in Comput. Phys. Comm. 156 (2004) 283.

Unusual features:Depending on the parameters of the model, the program generates additional new code, compiles it and loads it dynamically.Running time:0.2 seconds     

Var: A program to calculate the semivariance function in three orthogonal planes

The geostatistical concept of semivariance is used in VAR to calculate and plot variograms in three orthogonal planes. Distances between all points of pairs are calculated and the vector-angles between them are resolved into components in the X - Y, Y - Z, and Z - X planes respectively. Semivariance values for each distance calculation are assigned to the appropriate angular sector in each plane and variograms for all sectors are plotted in all three orthogonal planes on a CDC CYBER 73 computer.     

RECPAM: a computer program for recursive partition and amalgamation for censored survival data and other situations frequently occurring in biostatistics. I. Methods and program features

The methodology of recursive partition and amalgamation in biostatistics is presented and a FORTRAN program for its implementation, RECPAM, is described. RECPAM can be used to obtain classifications of patients according to several criteria commonly occurring in clinical biostatistics: an example is prognostic classification based on survival data. Classes are defined by simple statements, expressed in clinical terms, about predictor variables (e.g. prognostic factors). Special features of RECPAM are: the possibility of implementing a variety of classification criteria, the integration of recursive partition and amalgamation, and the availability of several strategies for constructing classification trees. A simple example to illustrate input and output features is given. The scope and flexibility of RECPAM will be illustrated in greater detail in a subsequent paper.     

A computer program to calculate the elastic stress and displacement fields around an elliptical hole under any applied plane state of stress

A short résumé is given of the solution to the plane elastic problem of an elliptical hole under uniaxial tension at any angle. The expression for the stresses and displacements, for both plane stress and plane strain, are explicitly given, and, by superposition of an applied stress at 90° to the first applied stress, any two-dimensional stress state can be simulated. A computer program is presented, enabling numerical values of stress and displacements for such stress states to be calculated on the free surface and at discrete points in the field for any ellipse, including the sharp crack.     

MSurvPow: a FORTRAN program to calculate the sample size and power for cluster-randomized clinical trials with survival outcomes

Manatunga and Chen [A.K. Manatunga, S. Chen, Sample size estimation for survival outcomes in cluster-randomized studies with small cluster sizes, Biometrics 56 (2000) 616-621] proposed a method to estimate sample size and power for cluster-randomized studies where the primary outcome variable was survival time. The sample size formula was constructed by considering a bivariate marginal distribution (Clayton-Oakes model) with univariate exponential marginal distributions. In this paper, a user-friendly FORTRAN 90 program was provided to implement this method and a simple example was used to illustrate the features of the program.     

A method to measure the degree of control per se in the oral glucose tolerance test

Using the glucose and insulin values from a 5-hr oral glucose tolerance test, nine quantitative measures have been developed to separate normal, "flat-curve," and non-insulin-dependent diabetic (NIDD) patients. The purpose of these measures is to quantify per se the degree of control operating in glucose homeostasis. A control index which is based upon Swan's minimizing principle and uses only the glucose values was successful in assessing the degree of control operating in glucose homeostasis.