Simulation for population analysis of Michaelis-Menten elimination kinetics

A simulation study was conducted to compare the cost and performance of various models for population analysis of the steady state pharmacokinetic data arising from a one-compartment model with Michaelis-Menten elimination. The usual Michaelis-Menten model (MM) and its variants provide no estimate of the volume of distribution, and generally give poor estimates of the maximal elimination rate and the Michaelis-Menten constant. The exact solution to the Michaelis-Menten differential equation (TRUE) requires a precise analysis method designed for estimation of population pharmacokinetic parameters (the first-order conditional estimation method) and also considerable computational time to estimate population mean parameters accurately. The one-compartment model with dose-dependent clearance (DDCL), in conjunction with the first-order conditional estimation or Laplacian method, ran approximately 20-fold faster than TRUE and gave accurate population mean parameters for a drug having a long biological half-life relative to the dosing interval. These findings suggest that the well-known MM and its variants should be used carefully for the analysis of blood concentrations of a drug with Michaelis-Menten elimination kinetics, and that TRUE, in conjunction with a precise analysis method, should be considered for estimating population pharmacokinetic parameters. In addition, DDCL is a promising alternative to TRUE with respect to computation time, when the dosing interval is short relative to the biological half-life of a drug. This work was supported in part by the Epilepsy Research Foundation, the Nakatomi Foundation, and a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan.     

用计算机拟合法制作ALT标准曲线

用赖氏法重复测丙氨酸氨基转移酶（ＡＬＴ）标准曲线１０次，计算机作线性回归和曲线拟合。直线回归结果，酶活性在不高于９７Ｕ的范围内，相关系数（Ｒ）＝０．９９９，斜率（ｂ）＋２．５５×１０＾－３，截距（ａ）＝０．０２８６；而达到２００Ｕ时，Ｒ＝０．０８６，ｂ＝１．９０×１０＾－３，ａ＝０．０６６，，显著性检验两者之间差别为极显著。表明：９７Ｕ以下线性较好但不过原点，大于９７Ｕ之后开始明显偏离该线性。拟合     

片剂含量均匀度计量检验新方案的研究

本文通过大量测试工作,查明10批国产小剂量片剂的含量分布,在此基础上提出了计量检验新方案。采用计算机模拟随机抽样的方法,通过计算绘制了USP XX,BP,JP和新方案在正态分布和10批实际分布下的OC曲线。结果表明,当用于测定生产规模的片剂批时,与国外片剂含量均匀度计数检验方案中统计特性最优的USP XX方案相比,新方案NEW能在化验工作量相近的前提下,作出更准确的判断;新方案SMA能在不降低判断准确性的前提下,减少化验工作虽约三分之一。新方案还可减免分析方法误差对判定结果的影响。     

基于“互联网+”的《临床检验仪器学》虚拟仿真教学实践

《临床检验仪器学》是一门实践性课程,为改变目前教学中实验场地局限、大型自动化检测仪器缺乏等限制,提出《临床检验仪器学》虚拟仿真教学探索思路。本文基于医学检验应用型人才培养目标,形成检验仪器学单个仪器和综合项目训练的虚拟仿真教学设计与管理举措;构建教学效果评价与质量监控的方法,显著提高学生的自主学习能力和综合实践能力;借助互联网共享优势促进医学检验实验教学的内涵建设。     

高效液相色谱分析虚拟仿真教学实施及效果评价

目的 研究传统教学结合虚拟仿真教学在高效液相色谱法中进行药物含量分析的教学效果。方法 以2016级两个平行班的学生为研究对象,分为试验组（44名）和对照组（38名）。以高效液相色谱法分析甲硝唑注射液含量及其方法学研究为例,试验组采用传统线下教学结合虚拟仿真教学,对照组采用传统线下教学。通过比较两组期中、期末考试成绩来评价两组教学效果。用SPSS 22.0软件进行独立样本t检验。结果 期中测试结果表明试验组在实际操作考核方面优于对照组[（17.98±6.75） vs. （14.03±5.92）],差异有统计学意义（P < 0.05）,而在理论、汇报及报告成绩方面两组差异无统计学意义。两组期末考试成绩各方面差异都无统计学意义。结论 采用传统线下教学结合虚拟仿真训练,可提高学生的实际操作能力,有助于提高药物含量分析实验的教学效果。通过本项目的训练,学生掌握了高效液相色谱法操作、药物制剂的含量测定、分析方法的验证、数据处理及分析报告的撰写等能力,具备了一定的实际分析工作能力。     

基于PBL的情景模拟教学在重症医学科住院医师规范化培训中的应用

目的 探讨基于以问题为基础的学习（problem-based learning,PBL）的情景模拟教学在重症医学科住院医师规范化培训中的作用和效果。方法 选取2019年3月至2019年12月在苏州大学附属第一医院重症医学科规范化培训的住院医师48人,分为试验组和对照组,每组各24人。试验组采用基于PBL的情景模拟教学,对照组采用传统教学。教学任务结束后比较两组规培学员成绩,对比和分析调查问卷结果差异。应用SPSS 17.0进行t 检验。结果 试验组的理论考核成绩（85.50±5.15）分和技能考核成绩（82.38±5.64）分均高于对照组[（77.04±8.69）分、（70.92±5.65）分],差异有统计学意义（P<0.05）。试验组在提升学习兴趣和效率、提高临床工作能力、强化临床思维能力、提高团队协作能力和提高医患沟通能力等5个方面均高于对照组,差异有统计学意义（P<0.05）。结论 基于PBL的情景模拟与传统教学相比优势明显,值得推广。     

Kubicek每搏心输出量计算公式的三维有限元仿真研究

我们从 Kubicek模型三维有限元仿真的角度对 Kubicek每搏心输出量计算公式的临床应用价值进行了研究。在计算机仿真研究中 ,我们对比了模型仿真结果、具体采用 Kubicek每搏心输出量计算公式所得结果以及所设模型的理论计算结果。仿真结果表明 :模型中阻抗改变与主动脉中血液容积改变之间存在着近似的线性关系 ,证明了 Kubicek每搏心输出量计算公式具有一定的临床应用价值 ,同时也为心阻抗血流图基础理论提供了新的研究途径。     

Computer simulations and the use of radiolabelled sulphur colloid to measure the efficiency of the mononuclear phagocyte system

Technique are described whereby the clearance of the radiolabelled blood borne colloid can be continuously and reproducibly measured non-invasively from the same animal in vivo or from the isolated perfused intact liver in vitro. Using these techniques, the rate of removal of radiolabelled sulphur colloid by the mononuclear phagocytes in vivo and in vitro was shown to be biexponential. The pattern of clearance of colloid and the factors contributing to this were analysed with the aid of a computer program which mimicked the in vitro liver perfusion.     

The Validity of the Neale and Kendler Model-Fitting Approach in Examining the Etiology of Comorbidity

Given that knowledge regarding the etiology of comorbidity between disorders can have a significant impact on research regarding the classification, treatment, and etiology of the disorders, the ability to reject incorrect hypotheses regarding the causes of comorbidity is very important. A simulation study was conducted to assess the validity of the Neale and Kendler (1995) model-fitting approach in examining the etiology of comorbidity between two disorders. First, data were simulated under the assumptions of the 13 alternative comorbidity models described by Neale and Kendler. Second, model-fitting analyses testing the comorbidity models were conducted on the simulated datasets. Thirteen sets of data with varying model parameters were simulated to test Neale and Kendler's assertion that their model-fitting approach is appropriate across a range of potential prevalences and degrees of familiality. The validity of the model-fitting approach in examining unselected twin data and a combination of selected family data and unselected family data was explored. The model-fitting approach successfully discriminated several classes of comorbidity models, although discrimination between models within classes of related models was less accurate. Results suggest that the model-fitting approach can be a useful tool in examining the etiology of the comorbidity between disorders if the caveats of the present study's results are considered carefully. As predicted by Neale and Kendler, variations in the disorder prevalences and familial correlations did not affect the validity of their model-fitting approach, but affected the power to discriminate the correct model. As suggested by Neale and Kendler, the model-fitting approach can be applied to both unselected and selected data and to both twin and family data.     

Voronoi Polyhedra Analysis of Optimized Arterial Tree Models

Topological and metric properties of Voronoi polyhedra (VP) generated by the distal end points of terminal segments in arterial tree models grown by the method of constrained constructive optimization (CCO) are analyzed with the aim to characterize the spatial distribution of their supply sites relative to randomly distributed points as a reference model. The distributions of the number N _f of Voronoi cell faces, cell volume V, surface area S, area A of individual cell faces, and asphericity parameter of the CCO models are all significantly different from the ones of random points, whereas the distributions of V, S, and are also significantly different among CCO models optimized for minimum intravascular volume and minimum segment length (p < 0.0001). The distributions of N _f , V, and S of the CCO models are reasonably well approximated by two-parameter gamma distributions. We study scaling of intravascular blood volume and arterial cross-sectional area with the volume of supplied tissue, the latter being represented by the VP of the respective terminal segments. We observe scaling exponents from 1.20 ± 0.007 to 1.08 ± 0.005 for intravascular blood volume and 0.77 ± 0.01 for arterial cross-sectional area. Setting terminal flows proportional to the associated VP volumes during tree construction yields a relative dispersion of terminal flows of 37% and a coefficient of skewness of 1.12. © 2003 Biomedical Engineering Society. PAC2003: 8719Uv, 8710+e, 4720Ky, 0260Pn, 0230Oz