scholarly journals A Comparison of Minimal Pharmacokinetic Models for an Anti-diabetic Agent

2018 ◽  
Vol 1 ◽  
pp. 5
Author(s):  
May Anne E. Mata
Keyword(s):  
Plasma Concentration ◽  
Information Criterion ◽  
Drug Dosage ◽  
Statistical Information ◽  
Multiple Drug ◽  
Parameter Estimates ◽  
Time Interval ◽  
Pharmacokinetic Models ◽  
Nonlinear Regression Analysis ◽  
Estimate Rate

In diabetes studies, pharmacologists rely on statistical techniques tied with experimental results to describe the plasma concentration of an anti-diabetic agent. However, these sets of statistical information only provide minimal inference to the drug’s kinetics. To understand the effect of an anti-diabetic agent to a glucose-insulin system, it is necessary to predict its movement in the system over a specific time interval. In this study, a set of simple pharmacokinetic models was formulated to describe the dynamics of the plasma concentration of an anti-diabetic agent known as metformin. The models were fitted to empirical data via nonlinear regression analysis and were compared using Akaike information criterion to determine the most reasonable model and parameter estimates. The results reveal that models considering varying absorption rate have a promising fit. These models can be extended to multiple drug dosage cases and can be used to estimate rate constants associated to other anti-diabetic agents. Read full article here.

scholarly journals Maximum Likelihood Analysis of Rare Binary Traits Under Different Modes of Inheritance

Genetics ◽  
1996 ◽  
Vol 143 (4) ◽  
pp. 1819-1829 ◽  
Author(s):  
G Thaller ◽  
L Dempfle ◽  
I Hoeschele
Keyword(s):  
Maximum Likelihood ◽  
Mixed Model ◽  
Major Gene ◽  
Likelihood Ratio Statistic ◽  
Information Criterion ◽  
Genetic Models ◽  
Parameter Estimates ◽  
Gene Effects ◽  
Binary Traits ◽  
Deterministic Algorithms

Abstract Maximum likelihood methodology was applied to determine the mode of inheritance of rare binary traits with data structures typical for swine populations. The genetic models considered included a monogenic, a digenic, a polygenic, and three mixed polygenic and major gene models. The main emphasis was on the detection of major genes acting on a polygenic background. Deterministic algorithms were employed to integrate and maximize likelihoods. A simulation study was conducted to evaluate model selection and parameter estimation. Three designs were simulated that differed in the number of sires/number of dams within sires (10/10, 30/30, 100/30). Major gene effects of at least one SD of the liability were detected with satisfactory power under the mixed model of inheritance, except for the smallest design. Parameter estimates were empirically unbiased with acceptable standard errors, except for the smallest design, and allowed to distinguish clearly between the genetic models. Distributions of the likelihood ratio statistic were evaluated empirically, because asymptotic theory did not hold. For each simulation model, the Average Information Criterion was computed for all models of analysis. The model with the smallest value was chosen as the best model and was equal to the true model in almost every case studied.

Kinetics and physiological characteristics of autotrophic dentrification by denitrifying sulfur bacteria

2000 ◽  
Vol 42 (3-4) ◽  
pp. 59-68 ◽  
Author(s):  
S.-E. Oh ◽  
K.-S. Kim ◽  
H.-C. Choi ◽  
J. Cho ◽  
I.S. Kim
Keyword(s):  
Gas Production ◽  
Parameter Estimates ◽  
Production Volume ◽  
Autotrophic Denitrification ◽  
Nonlinear Regression Analysis ◽  
Monod Equation ◽  
Sulfur Bacteria ◽  
The Media ◽  
Parameter Values ◽  
Mixotrophic Conditions

To study the kinetics and physiology of autotrophic denitrifying sulfur bacteria, a steady-state anaerobic master culture reactor (MCR) was operated for over six months under a semi-continuous mode and nitrate limiting conditions using nutrient/mineral/buffer (NMB) medium containing thiosulfate and nitrate. Characteristics of the autotropic denitrifier were investigated through the cumulative gas production volume and rate, measured using an anaerobic respirometer, and through the nitrate, nitrite, and sulfate concentrations within the media. The bio-kinetic parameters were obtained based upon the Monod equation using mixed cultures in the MCR. Nonlinear regression analysis was employed using nitrate depletion and biomass production curves. Although this analysis did not yield exact biokinetic parameter estimates, the following ranges for the parameter values were obtained: μmax =0.12-0.2 hr-1; k=0.3-0.4 hr-1; Ks=3-10mg/L; YNO3=0.4-0.5mg Biomass/mg NO3--N. Inhibition of denitrification occurred when the concentrations of NO3--N, and SO42- reached about 660mg/L and 2,000mg/L, respectively. The autotrophic denitrifying sulfur bacteria were observed to be very sensitive to nitrite but relatively tolerant of nitrate, sulfate, and thiosulfate. Under mixotrophic conditions, denitrification by these bacteria occurred autotrophically; even with as high as 2 g COD, autotrophic denitrification was not significantly affected. The optimal pH and temperature for autotrophic denitrification was about 6.5–7.5 and 33–35 °C, respectively.

scholarly journals Longitudinal Pattern of Aerenchyma Formation Using the Ti-Gompertz Model in Rice Adventitious Roots

2021 ◽  
Vol 12 ◽  
Author(s):  
Yun Chen ◽  
Guoming Li ◽  
Buhong Zhao ◽  
Yajun Zhang ◽  
Kun Liu ◽  
...  
Keyword(s):  
Adventitious Roots ◽  
Goodness Of Fit ◽  
Gompertz Model ◽  
Root Apex ◽  
Information Criterion ◽  
Ordinary Least Squares ◽  
Parameter Estimates ◽  
Aerenchyma Formation ◽  
Root Aerenchyma ◽  
Longitudinal Pattern

The longitudinal pattern of root aerenchyma formation of its relationship with the function of adventitious roots in rice remains unclear. In this study, the percentage of the aerenchyma area to the cross-sectional area (i.e., aerenchyma percentage) was fit with four non-linear models, namely, W0-Gompertz, Ti-Gompertz, logistic, and von Bertalanffy. Goodness-of-fit criteria such as the R2, the Akaike information criterion (AIC), and the Bayesian information criterion (BIC) were used to select the model. The bias of the parameters was evaluated using the difference between the ordinary least squares-based parameter estimates and the mean of 1,000 bootstrap-based parameter estimates and the symmetry of the distributions of these parameters. The results showed that the Ti-Gompertz model, which had a high goodness-of-fit with an R2 close to 1, lower AIC and BIC values, parameter estimates close to being unbiased, and good linear approximation, provided the best fit for the longitude pattern of rice aerenchyma formation with different root lengths among the competing models. Using the second- and third-order derivatives according to the distance from the root apex, the critical points of Ti-Gompertz were calculated. The rapid stage for aerenchyma formation was from the maximum acceleration point (1.38–1.76 cm from the root apex) to the maximum deceleration point (3.13–4.19 cm from the root apex). In this stage, the aerenchyma percentage increased by 5.3–15.7% per cm, suggesting that the cortical cells tended to die rapidly for the aerenchyma formation rather than for the respiration cost during this stage. Meanwhile, the volume of the aerenchyma of the entire roots could be computed using the integral function of the Ti-Gompertz model. We proposed that the longitudinal pattern of root aerenchyma formation modeled by the Ti-Gompertz model helped to deeply understand the relationship between the anatomical traits and physiological function in rice adventitious roots.

scholarly journals Population Pharmacokinetic Modeling and Pharmacodynamic Target Attainment Simulation of Piperacillin/Tazobactam for Dosing Optimization in Late Elderly Patients with Pneumonia

Antibiotics ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 113 ◽  
Author(s):  
Noriyuki Ishihara ◽  
Nobuhiro Nishimura ◽  
Kazuro Ikawa ◽  
Fumi Karino ◽  
Kiyotaka Miura ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Elderly Patients ◽  
Distribution Volume ◽  
Population Pharmacokinetic ◽  
Parameter Estimates ◽  
Target Attainment ◽  
Old Patients ◽  
Final Model ◽  
Concentration Time ◽  
Population Pk

The aim of this study was to develop a population pharmacokinetic model for piperacillin (PIPC)/tazobactam (TAZ) in late elderly patients with pneumonia and to optimize the administration planning by applying pharmacokinetic/pharmacodynamic (PK/PD) criteria. PIPC/TAZ (total dose of 2.25 or 4.5 g) was infused intravenously three times daily to Japanese patients over 75 years old. The plasma concentrations of PIPC and TAZ were determined using high-performance liquid chromatography and modeled using the NONMEM program. PK/PD analysis with a random simulation was conducted using the final population PK model to estimate the probability of target attainment (PTA) profiles for various PIPC/TAZ-regimen–minimum-inhibitory-concentration (MIC) combinations. The PTAs for PIPC and TAZ were determined as the fraction that achieved at least 50% free time > MIC and area under the free-plasma-concentration–time curve over 24 h ≥ 96 μg h/mL, respectively. A total of 18 cases, the mean age of which was 86.5 ± 6.0 (75–101) years, were investigated. The plasma-concentration–time profiles of PIPC and TAZ were characterized by a two-compartment model. The parameter estimates for the final model, namely the total clearance, central distribution volume, peripheral distribution volume, and intercompartmental clearance, were 4.58 + 0.061 × (CLcr − 37.4) L/h, 5.39 L, 6.96 L, and 20.7 L/h for PIPC, and 5.00 + 0.059 × (CLcr − 37.4) L/h, 6.29 L, 7.73 L, and 24.0 L/h for TAZ, respectively, where CLcr is the creatinine clearance. PK/PD analysis using the final model showed that in drug-resistant strains with a MIC > 8 μg/mL, 4.5 g of PIPC/TAZ every 6 h was required, even for the patients with a CLcr of 50–60 mL/min. The population PK model developed in this study, together with MIC value, can be useful for optimizing the PIPC/TAZ dosage in the over-75-year-old patients, when they are administered PIPC/TAZ. Therefore, the findings of present study may contribute to improving the efficacy and safety of the administration of PIPC/TAZ therapy in late elderly patients with pneumonia.

scholarly journals DELINEATION OF HOMOGENEOUS ZONES BASED ON GEOSTATISTICAL MODELS ROBUST TO OUTLIERS

2019 ◽  
Vol 32 (2) ◽  
pp. 472-481
Author(s):  
DANILO PEREIRA BARBOSA ◽  
EDUARDO LEONEL BOTTEGA ◽  
DOMINGOS SÁRVIO MAGALHÃES VALENTE ◽  
NERILSON TERRA SANTOS ◽  
WELLINGTON DONIZETE GUIMARÃES
Keyword(s):  
Linear Models ◽  
Information Criterion ◽  
Physicochemical Characteristics ◽  
Parameter Estimates ◽  
Mixed Linear Models ◽  
Management Zones ◽  
Geostatistical Models ◽  
Apparent Electrical Conductivity ◽  
External Drift ◽  
Theory And Model

ABSTRACT Measures of the apparent electrical conductivity (ECa) of soil are used in many studies as indicators of spatial variability in physicochemical characteristics of production fields. Based on these measures, management zones (MZs) are delineated to improve agricultural management. However, these measures include outliers. The presence or incorrect identification and exclusion of outliers affect the variogram function and result in unreliable parameter estimates. Thus, the aim of this study was to model ECa data with outliers using methods based on robust approximation theory and model-based geostatistics to delineate MZs. Robust estimators developed by Cressie-Hawkins, Genton and MAD Dowd were tested. The Cressie-Hawkins semivariance estimator was selected, followed by the semivariogram cubic fit using Akaike information criterion (AIC). The robust kriging with an external drift plug-in was applied to fitted estimates, and the fuzzy k-means classifier was applied to the resulting ECa kriging map. Models with multiple MZs were evaluated using fuzzy k-means, and a map with two MZs was selected based on the fuzzy performance index (FPI), modified partition entropy (MPE) and Fukuyama-Sugeno and Xie-Beni indices. The defined MZs were validated based on differences between the ECa means using mixed linear models. The independent errors model was chosen for validation based on its AIC value. Thus, the results demonstrate that it is possible to delineate an MZ map without outlier exclusion, evidencing the efficacy of this methodology.

Modeling of respiratory system impedances in dogs

1987 ◽  
Vol 62 (2) ◽  
pp. 414-420 ◽  
Author(s):  
A. C. Jackson ◽  
K. R. Lutchen
Keyword(s):  
Respiratory System ◽  
Element Model ◽  
Parameter Estimates ◽  
Frequency Range ◽  
Nonlinear Regression Analysis ◽  
Entire Frequency Range ◽  
Frequency Dependent ◽  
Impedance Data ◽  
Parameter Values ◽  
Gas Compressibility

Mechanical impedances between 4 and 64 Hz of the respiratory system in dogs have been reported (A.C. Jackson et al. J. Appl. Physiol. 57: 34–39, 1984) previously by this laboratory. It was observed that resistance (the real part of impedance) decreased slightly with frequency between 4 and 22 Hz then increased considerably with frequency above 22 Hz. In the current study, these impedance data were analyzed using nonlinear regression analysis incorporating several different lumped linear element models. The five-element model of Eyles and Pimmel (IEEE Trans. Biomed. Eng. 28: 313–317, 1981) could only fit data where resistance decreased with frequency. However, when the model was applied to these data the returned parameter estimates were not physiologically realistic. Over the entire frequency range, a significantly improved fit was obtained with the six-element model of DuBois et al. (J. Appl. Physiol. 8: 587–594, 1956), since it could follow the predominate frequency-dependent characteristic that was the increase in resistance. The resulting parameter estimates suggested that the shunt compliance represents alveolar gas compressibility, the central branch represents airways, and the peripheral branch represents lung and chest wall tissues. This six-element model could not fit, with the same set of parameter values, both the frequency-dependent decrease in Rrs and the frequency-dependent increase in resistance. A nine-element model recently proposed by Peslin et al. (J. Appl. Physiol. 39: 523–534, 1975) was capable of fitting both the frequency-dependent decrease and the frequency-dependent increase in resistance. However, the data only between 4 and 64 Hz was not sufficient to consistently determine unique values for all nine parameters.

scholarly journals International migration beyond gravity: A statistical model for use in population projections

2008 ◽  
Vol 105 (40) ◽  
pp. 15269-15274 ◽  
Author(s):  
Joel E. Cohen ◽  
Marta Roig ◽  
Daniel C. Reuman ◽  
Cai GoGwilt
Keyword(s):  
International Migration ◽  
Generalized Linear Model ◽  
Bayesian Information Criterion ◽  
Information Criterion ◽  
Population Projections ◽  
Parameter Estimates ◽  
Independent Variables ◽  
Indicator Variables ◽  
Starting Model ◽  
Country Specific

International migration will play an increasing role in the demographic future of most nations if fertility continues to decline globally. We developed an algorithm to project future numbers of international migrants from any country or region to any other. The proposed generalized linear model (GLM) used geographic and demographic independent variables only (the population and area of origins and destinations of migrants, the distance between origin and destination, the calendar year, and indicator variables to quantify nonrandom characteristics of individual countries). The dependent variable, yearly numbers of migrants, was quantified by 43653 reports from 11 countries of migration from 228 origins and to 195 destinations during 1960–2004. The final GLM based on all data was selected by the Bayesian information criterion. The number of migrants per year from origin to destination was proportional to (population of origin)0.86(area of origin)−0.21(population of destination)0.36(distance)−0.97, multiplied by functions of year and country-specific indicator variables. The number of emigrants from an origin depended on both its population and its population density. For a variable initial year and a fixed terminal year 2004, the parameter estimates appeared stable. Multiple R2, the fraction of variation in log numbers of migrants accounted for by the starting model, improved gradually with recentness of the data: R2 = 0.57 for data from 1960 to 2004, R2 = 0.59 for 1985–2004, R2 = 0.61 for 1995–2004, and R2 = 0.64 for 2000–2004. The migration estimates generated by the model may be embedded in deterministic or stochastic population projections.

Impact of low percentage of data below the quantification limit on parameter estimates of pharmacokinetic models

2011 ◽  
Vol 38 (4) ◽  
pp. 423-432 ◽  
Author(s):  
Xu Steven Xu ◽  
Adrian Dunne ◽  
Holly Kimko ◽  
Partha Nandy ◽  
An Vermeulen
Keyword(s):  
Parameter Estimates ◽  
Pharmacokinetic Models ◽  
Quantification Limit

scholarly journals DISTRIBUTION OF TRAFFIC SPEED IN DIFFERENT TRAFFIC CONDITIONS: AN EMPIRICAL STUDY IN BUDAPEST

Transport ◽  
2020 ◽  
Vol 35 (1) ◽  
pp. 68-86 ◽  
Author(s):  
Mohammad Maghrour Zefreh ◽  
Ádám Török
Keyword(s):  
Traffic Flow ◽  
Traffic Engineering ◽  
Goodness Of Fit ◽  
Graphical Representation ◽  
Information Criterion ◽  
Traffic Density ◽  
Time Interval ◽  
Fundamental Diagram ◽  
Traffic Conditions ◽  
Traffic Speed

Fundamental diagram, a graphical representation of the relationship among traffic flow, speed, and density, has been the foundation of traffic flow theory and transportation engineering for many years. Underlying a fundamental diagram is the relation between traffic speed and density, which serves as the basis to understand system dynamics. Empirical observations of the traffic speed versus traffic density show a wide-scattering of traffic speeds over a certain level of density, which would form a speed distribution over a certain level of density. The main aim of the current research is to study on the distribution of traffic speed in different traffic conditions in the urban roads since the distribution of traffic speed is necessary for many traffic engineering applications including generating traffic in micro-simulation systems. To do so, the traffic stream is videotaped at various locations in the city of Budapest (Hungary). The recorded videos were analysed by traffic engineering experts and different traffic conditions were extracted from these recorded videos based on the predefined scenarios. Then their relevant speeds in that time interval were estimated with the so-called “g-estimator method” using the outputs of the available loop detectors among the videotaped locations. Then different parametric candidate distributions have been fitted to the speeds by Maximum Likelihood Estimation (MLE) method. Having fitted different parametric distributions to speed data, they were compared by three goodness-of-fit tests along with two penalized criteria (Akaike Information Criterion – AIC and Bayesian Information Criterion – BIC) in order to overcome the over-fitting problems. The results showed that the speed of traffic flow follows exponential, normal, lognormal, gamma, beta and chisquare distribution in the condition that traffic flow followed over-saturated congestion, under saturated flow, free flow, congestion, accelerated flow and decelerated flow respectively.

scholarly journals Drug Interaction Management in Critically Ill Patient

2021 ◽  
pp. 396-416
Author(s):  
Hemraj Singh Rajput ◽  
Nirmal V. Shah
Keyword(s):  
Drug Interaction ◽  
Drug Interactions ◽  
Critically Ill ◽  
Clinical Pharmacist ◽  
Alternative Therapy ◽  
Drug Dosage ◽  
Critically Ill Patient ◽  
Time Interval ◽  
Patient Health ◽  
Interaction Management

Drug interaction in critically ill patient is very common and affecting patients Physically, Mentally and Financially. There are various measures which has been taken to minimize this burden on patient, such as books being prepared which include various drug interaction, maintain websites and database that provides information regarding drug interactions. With the use of these website and databases the drug interaction can be managed. It is common practice that side effects of drug interaction are being managed by additional drugs, the main reason behind it could be non-availability of alternative drugs or costlier alternative. These factors remain the main cause of treatment failure in majority of patients leading to prolong. The current study was performed for the duration of 12 months, from this study it was identified that 113 types of major drug interactions commonly found in total 250 prescriptions which were evaluated and managed accordingly. Suggestions being prescribed by various sites were, avoid concomitant use of drug, use alternative therapy, and monitor closely for any adverse effect. During suggestion made by the Clinical Pharmacist, for the same drug interactions it was identified that more of drug therapy adjustment can be done then provided by the online database. The parameter on which the drug interactions management are being suggested were focused on just type of drug interaction and its effect, it does not include the actual pharmacodynamic and pharmacokinetic changes in therapy. The suggestion made by the clinical pharmacist were includes drug removal, drug dosage changes, alternative therapy, alternative route of administration, change in time interval etc. From this study it was concluded that the drug interaction management can be done at various stages of treatment with proper therapy modification by the clinical pharmacist, and if done properly it will improve the overall outcome of patient health care.

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