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Derived Parameters (derived + parameter)
Selected AbstractsRobust improvements in fasting and prandial measures of ,-cell function with vildagliptin in drug-naïve patients: analysis of pooled vildagliptin monotherapy databaseDIABETES OBESITY & METABOLISM, Issue 10 2008R. E. Pratley Aim:, To assess the effects of 24-week treatment with vildagliptin on measures of ,-cell function in a broad spectrum of drug-naïve patients with type 2 diabetes (T2DM). Methods:, Data from all double-blind, multicentre, randomized, placebo- or active-controlled trials conducted in drug-naïve patients with T2DM were pooled from all patients receiving monotherapy with vildagliptin (100 mg daily: 50 mg twice daily or 100 mg once daily, n = 1855) or placebo (n = 347). Fasting measures of ,-cell function [homeostasis model assessment of ,-cell function (HOMA-B) and proinsulin : insulin ratio] were assessed in the overall pooled monotherapy population. Standard meal tests were performed at baseline and week 24 in a subset of patients, and effects of vildagliptin (100 mg daily, n = 227) on dynamic (meal test,derived) measures of ,-cell function [insulin secretion rate relative to glucose (ISR/G) and insulinogenic indices] were assessed relative to baseline and vs. placebo (n = 29). Results:, In the overall population, vildagliptin significantly increased HOMA-B both relative to baseline [adjusted mean change (AM,) = 10.3 ± 1.5] and vs. placebo (between-treatment difference in AM, = 11.5 ± 4.5, p = 0.01) and significantly decreased the proinsulin : insulin ratio relative to baseline (AM, = ,0.05 ± 0.01) and vs. placebo (between-treatment difference in AM, = ,0.09 ± 0.02, p < 0.001). Relative to baseline, vildagliptin monotherapy significantly increased all meal test,derived parameters, and ISR/G (between-treatment difference in AM, = 9.8 ± 2.8 pmol/min/m2/mM, p < 0.001) and the insulinogenic index0,peak glucose (between-treatment difference in AM, = 0.24 ± 0.05 pmol/mmol, p = 0.045) were significantly increased vs. placebo. Conclusions:, Vildagliptin monotherapy consistently produced robust improvements in both fasting and meal test,derived measures of ,-cell function across a broad spectrum of drug-naïve patients with T2DM. All Phase III trials described (NCT 00099905, NCT 00099866, NCT 00099918, NCT 00101673, NCT 00101803 and NCT 00120536) are registered with ClinicalTrials.gov. [source] A population-based model of the nonlinear dynamics of the thalamocortical feedback network displays intrinsic oscillations in the spindling (7,14 Hz) rangeEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2005Nada A. B. Yousif Abstract The thalamocortical network is modelled using the Wilson,Cowan equations for neuronal population activity. We show that this population model with biologically derived parameters possesses intrinsic nonlinear oscillatory dynamics, and that the frequency of oscillation lies within the spindle range. Spindle oscillations are an early sleep oscillation characterized by high-frequency bursts of action potentials followed by a period of quiescence, at a frequency of 7,14 Hz. Spindles are generally regarded as being generated by intrathalamic circuitry, as decorticated thalamic slices and the isolated thalamic reticular nucleus exhibit spindles. However, the role of cortical feedback has been shown to regulate and synchronize the oscillation. Previous modelling studies have mainly used conductance-based models and hence the mechanism relied upon the inclusion of ionic currents, particularly the T-type calcium current. Here we demonstrate that spindle-frequency oscillatory activity can also arise from the nonlinear dynamics of the thalamocortical circuit, and we use bifurcation analysis to examine the robustness of this oscillation in terms of the functional range of the parameters used in the model. The results suggest that the thalamocortical circuit has intrinsic nonlinear population dynamics which are capable of providing robust support for oscillatory activity within the frequency range of spindle oscillations. [source] Transcription factor 7,like 2 polymorphism modulates glucose and lipid homeostasis, adipokine profile, and hepatocyte apoptosis in NASH,HEPATOLOGY, Issue 2 2009Giovanni Musso Genetic factors underlying the association of NAFLD with diabetes and atherosclerosis are unknown. Recent human studies suggest transcription factor 7,like 2 (TCF7L2) polymorphism predisposes to diabetes through modulation of ,-cell function and modulates lipid levels in familial dyslipidemia. Emerging experimental evidence connects TCF7L2 to adipocyte metabolism and lipid homeostasis, as well. We tested if TCF7L2 polymorphism is a risk factor for nonalcoholic fatty liver disease (NAFLD) and if it modulates liver injury, glucose homeostasis, lipoprotein, and adipokine profiles in NASH. TCF7L2 genotype and dietary habits of 78 nondiabetic normolipidemic NAFLD subjects and 156 age-, body mass index,, sex-matched healthy controls were assessed. In 39 biopsy-proven nonalcoholic steatohepatitis (NASH) and matched controls TCF7L2 polymorphism was correlated to liver histology and oral glucose tolerance test,derived parameters of glucose homeostasis. Patients with NASH and controls consumed a high-fat meal and TCF7L2 genotype was correlated to postprandial circulating lipoproteins, adipokines, and cytokeratin-18 fragments. The TCF7L2 CT/TT genotype was more frequent in NAFLD and predicted the presence and severity of liver disease, of ,-cell dysfunction, of reduced incretin effect and hepatic insulin resistance in NASH; it also modulated postprandial hepatocyte apoptosis, lipoproteins, and adipokine profiles in both groups. Conclusion: TCF7L2 polymorphism predisposes to NAFLD and significantly impacts liver injury, glucose homeostasis, and postprandial lipoprotein and adipokine responses to fat ingestion. This polymorphism also modulates a fat-induced increase in circulating markers of hepatocyte apoptosis in NASH. Targeting postprandial lipemia, at least in at-risk TCF7L2 genotypes, may improve liver disease and glucose dysmetabolism in these patients. (HEPATOLOGY 2008.) [source] Meta-analysis of pharmacokinetic data of veterinary drugs using the Food Animal Residue Avoidance Databank: oxytetracycline and procaine penicillin GJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2004A. L. Craigmill Investigators frequently face the quandary of how to interpret the oftentimes disparate pharmacokinetic parameter values reported in the literature. Combining of data from multiple studies (meta-analysis) is a useful tool in pharmacokinetics. Few studies have explored the use of meta-analysis for veterinary species. Even fewer studies have explored the potential strengths and weaknesses of the various methods of performing a meta-analysis. Therefore, in this study we performed a meta-analysis for oxytetracycline (OTC) and procaine penicillin G (PPG) given intramuscularly to cattle. The analysis included 28 individual data sets from 18 published papers for PPG (288 data points), and 41 individual data sets from 25 published papers for OTC (489 data points). Three methods were used to calculate the parameters. The first was a simple statistical analysis of the parameter values reported in each paper. The second method was a standard Two-Stage Method (TSM) using the mean concentration vs. time data extracted from each paper. The third method was the use of nonlinear mixed effect modeling (NMEM) of the concentration vs. time data reported in the various papers, treating the mean data as if each set came from an individual animal. The results of this evaluation indicate that all three methods generate comparable mean parameter estimates for OTC and PPG. The only significant difference noted was for OTC absorption half-lives taken from the published literature, a difference attributable to the use of an alternative method of parameter calculation. The NMEM procedure offers the possibility of including covariates such as dose, age, and weight. In this study the covariates did not influence the derived parameters. A combination approach to meta-analysis of published mean data is recommended, where the TSM is the first step, followed by the NMEM approach. [source] Pulsational and evolutionary analysis of the double-mode RR Lyrae star BS ComMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 1 2008I. Dékány ABSTRACT We derive the basic physical parameters of the field double-mode RR Lyrae star BS Com from its observed periods and the requirement of consistency between the pulsational and evolutionary constraints. By using the current solar-scaled horizontal branch evolutionary models of Pietrinferni et al. and our linear non-adiabatic purely radiative pulsational models, we get M/M,= 0.698 ± 0.004, log(L/L,) = 1.712 ± 0.005, Teff= 6840 ± 14 K, [Fe/H]=,1.67 ± 0.01, where the errors are standard deviations assuming uniform age distribution along the full range of uncertainty in age. The last two parameters are in a good agreement with the ones derived from the observed BVIC colours and the updated atlas9 stellar atmosphere models. We get Teff= 6842 ± 10 K, [Fe/H]=,1.58 ± 0.11, where the errors are purely statistical ones. It is remarkable that the derived parameters are nearly independent of stellar age at early evolutionary stages. Later stages, corresponding to the evolution towards the asymptotic giant branch, are most probably excluded because the required high temperatures are less likely to satisfy the constraints posed by the colours. We also show that our conclusions are only weakly sensitive to non-linear period shifts predicted by current hydrodynamical models. [source] An unusual methylene aziridine refined in P21/c and the nonstandard setting P21/nACTA CRYSTALLOGRAPHICA SECTION C, Issue 12 2009George C. Feast The unusual methylene aziridine 6- tert -butyl-3-oxa-2-thia-1-azabicyclo[5.1.0]oct-6-ene 2,2-dioxide, C9H15NO3S, was found to crystallize with two molecules in the asymmetric unit. The structure was solved in both the approximately orthogonal and the oblique settings of space group No. 14, viz. P21/n and P21/c, respectively. A comparison of these results clearly displayed an increase in the correlation between coordinates in the ac plane for the oblique cell. The increase in the corresponding covariances makes a significant contribution to the standard uncertainties of derived parameters, e.g. bond lengths. Since there is yet no CIF definition for the full variance,covariance matrix, there are clear advantages to reporting the structure in the nonstandard space-group setting. [source] | ||||||||||