Performance in population models for count data,part II: A new SAEM algorithm

Analysis of count data from clinical trials using mixed effect analysis has recently become widely used. However, algorithms available for the parameter estimation, including LAPLACE and Gaussian quadrature (GQ), are associated with certain limitations, including bias in parameter estimates and the long analysis runtime. The stochastic approximation expectation maximization (SAEM) algorithm has proven to be a very efficient and powerful tool in the analysis of continuous data. The aim of this study was to implement and investigate the performance of a new SAEM algorithm for application to count data. A new SAEM algorithm was implemented in MATLAB for estimation of both, parameters and the Fisher information matrix. Stochastic Monte Carlo simulations followed by re-estimation were performed according to scenarios used in previous studies (part I) to investigate properties of alternative algorithms (Plan et al., 2008, Abstr 1372 []). A single scenario was used to explore six probability distribution models. For parameter estimation, the relative bias was less than 0.92% and 4.13% for fixed and random effects, for all models studied including ones accounting for over- or under-dispersion. Empirical and estimated relative standard errors were similar, with distance between them being <1.7% for all explored scenarios. The longest CPU time was 95 s for parameter estimation and 56 s for SE estimation. The SAEM algorithm was extended for analysis of count data. It provides accurate estimates of both, parameters and standard errors. The estimation is significantly faster compared to LAPLACE and GQ. The algorithm is implemented in Monolix 3.1, (beta-version available in July 2009).     

孕妇凝血指标的数学模型及指标异常变化警戒值探讨

目的探讨孕妇不同孕期凝血指标变化趋势的数学模型及凝血指标异常变化的警戒值估计,帮助临床医生及预防保健人员及早期发现高危人群,有效预防产科出血和凝血并发症的发生。方法对214例孕妇的孕期凝血指标进行回顾性追索,根据聚类分析的结果,建立方差分析、回归分析及ARIMA时间序列分析模型,比较各检测指标在不同孕期的变化规律。结果所建模型均能够很好的模拟不同孕期凝血指标的变化规律,结果显示:PLT指标值在孕晚期出现明显的下降(P0.05),PT与INR指标值在妊娠中期的下降明显(P0.01),APTT在整个妊娠期均下降(P0.01),FG指标值在妊娠晚期出现上升(P0.01),不同孕期凝血指标的警戒值表达式为:μ±2σ。结论所建模型能够较好的模拟不同孕期凝血指标变化规律,不同孕期凝血指标的正常参考值范围及异常警戒值具有一定的医学应用价值。     

化疗药物性静脉炎及渗漏损伤的动物实验模型研究概况

化疗药物性静脉炎及渗漏损伤的动物实验模型是研究体内化疗药物性静脉炎及渗漏损伤的发病机制和评价各种治疗方法的重要条件。化疗药物性静脉炎及渗漏损伤的实验研究进展缓慢,其主要原因是缺乏理想的动物模型。依文献报道,化疗药物性静脉炎模型主要以大白兔耳缘静脉注射长春瑞滨等化疗药物为多见,化疗药物渗漏损伤模型主要以大鼠及大白兔背部皮下注射盐酸阿霉素等化疗药物为多见。文章就近年来常用的一些化疗药物性静脉炎及渗漏损伤的动物模型综述如下。     

以新生儿重症监护病房为中心的早产儿视网膜病变筛查模式

目的：介绍一种较为完善的早产儿视网膜病变（ROP）筛查模式。方法：建立基本完善的ROP登记、会诊、筛查、转诊等制度,所有工作均在新生儿重症监护病房（N ICU）完成,形成以NICU为中心的ROP筛查模式,并按此模式开展筛查工作。结果：登记符合ROP筛查标准的患儿239例,其中接受至少一次筛查的患儿222例（占应筛查总数的92.89%）,按要求完成筛查的患儿176例（占应筛查总数的73.64%）。发现ROP患儿39例（占实际筛查数的17.57%）,其中阈值前期1型或阈值期病变11例（占实际筛查数的4.96%）。结论：这种以NICU为中心的ROP筛查模式,制度较为完善,临床中易于操作,能有效节约医疗资源,适合在中小城市中推广。     

灯盏细辛黄酮类成分对压力诱导的视网膜神经节细胞凋亡的影响

目的考察灯盏细辛中黄酮类成分(总黄酮、灯盏花素)对体外高压诱导的视网膜神经节细胞(retinal gan-glion cells,RGCs)凋亡的影响,探讨其视神经保护作用的物质基础。方法采用胰酶消化法将24只出生2~3d的SD(Sprague-Dawley)乳鼠视网膜制成细胞悬液,接种于经多聚鸟氨酸(HA)和层粘连蛋白(LN)包被的盖玻片中。培养72h后,将覆有细胞的血盖片转入加压装置中,加入黄酮类成分,继续培养48h,采用Fas蛋白免疫组化染色法及原位末端脱氧核苷酸转移酶标记(Tunel-POD)法进行检测,每天观察细胞形态,同时对部分细胞行NSE染色检查。结果细胞生长良好,NSE染色表明,85%以上的细胞为RGCs。给药组的Fas蛋白阳性表达指数和凋亡指数均明显低于模型组(P<0.05~0.01)。结论黄酮类成分均能对抗压力诱导的RGCs凋亡,为灯盏细辛视神经保护的有效组分。     

下颌第一磨牙三维有限元模型的建立

目的：建立下颌第一磨牙三维有限元模型。方法：通过螺旋CT扫描的方法，利用Mimics、Geomagic Studio 7等图像处理软件，HyperMesh网格自动划分软件，通过特定的MSC．MARC有限元软件建立下颌第一磨牙三维有限元模型。结果：准确的建立了牙本质、牙釉质、髓腔、牙槽骨、牙周膜等组织形态的三维有限元模型。结论：本实验建模方法可行性强，方便快捷，具有良好的生物力学与几何力学相似性。为临床口腔医师提供了一种简捷而精确的有限元建模方法。     

大鼠抗GBM肾炎模型的建立及不同病期的生化指标和肾组织病理学观察

目的：为研究人类新月体抗肾炎的发病机制，建立大鼠抗肾小球基底膜（BGM）肾炎的动物模型，方法：提取S－D大鼠GBM抗原，将此抗原免疫新西兰白兔获得抗血清，再将此抗血清从尾静脉一次性注射给S－D大鼠。实验分2组：肾炎模型组及正常对照组。定期于第4天、第14天第第21天检测大鼠24h尿蛋白，血肌酐及血尿素的含量和肾组织病理学改变。结果：大鼠肾炎模型组：大鼠注射抗血清后于第4天出现大量蛋白尿，第14天血肌酐，血尿素显著升高，并持续上升，肾组织病理表现为肾小球内细胞数明显增加，大量新月体形成及蛋白管型，GBM呈不规则增厚，足突融合，内皮细胞脱落，坏死，免疫荧光检查见IgG、鼠IgG沿GBM线形分布，大鼠正常对照组以上指标均无明显改变。结论：通过动态观察大鼠抗GBM肾炎的病变变化，证实该模型病变与人类新月体性肾炎的病变较为一致，该模型可用于探讨人类新月体体肾炎的实验研究。     

阻断大脑中动脉建立大鼠局灶性脑梗塞模型的观察

通过经颅阻断大鼠大脑中动脉制成局灶性脑缺血动物模型。大脑中动脉阻塞后大鼠均出现各种神经病学征象。氯化三苯基四氮唑染色发现梗塞区位于皮质及基底节。光镜和电镜观察大脑中动脉阻塞后脑组织的病理改变,发现梗塞区不同程度的细胞和间质变性坏死。结果表明该模型是比较理想的局灶性脑缺血模型.     

柯萨奇病毒诱发实验性多发性肌炎的初步研究

分别用不同量的柯萨奇病毒Ｂ１、２、３感染和兔肌匀浆加完全弗氏佐剂免疫正常豚鼠；拟建立多发性肌炎模型。结果发现：０．１ｍｌ毒力为１０－５ＴＣＩＤ５０柯萨奇病毒Ｂ１感染豚鼠组，３周后出现多发性肌炎症状。肌酶谱异常与其它组有明显差异，病理检查证实为多发性肌炎改变。单纯兔肌匀浆免疫对照组未发病。提示柯萨奇病毒Ｂ１感染及感染的病毒量与多发性肌炎的发病相关     

The influence of support conditions in the loading fixture on failure mechanisms in the push-out test: a finite element study

The usefulness of the push-out test as an indicator of interface strength was evaluated using finite element models of intact and partially failed cylindrical push-out specimens loaded against a rigid annular support. The irregular stress distributions that were found in intact specimens depended more on interface conditions at the loading fixture than on a 35% increase in interface area. The maximum stress at the interface was a tensile stress. Critical energy release rates for interface failure were calculated for flawed specimens in which flaw size was either 10 or 100 microns, and for boundary conditions at the loading fixture that were either fixed or slipping in the radial direction. The critical energy release rates depended heavily on the support boundary conditions. Thus, the results of parametric push-out tests can be reasonably compared only for specimens that are very similar in geometry and that are loaded in very carefully controlled fixtures.