Fisher information matrix for nonlinear mixed effects multiple response models: Evaluation of the appropriateness of the first order linearization using a pharmacokinetic/pharmacodynamic model

We focus on the Fisher information matrix used for design evaluation and optimization in nonlinear mixed effects multiple response models. We evaluate the appropriateness of its expression computed by linearization as proposed for a single response model. Using a pharmacokinetic–pharmacodynamic (PKPD) example, we first compare the computation of the Fisher information matrix with approximation to one derived from the observed matrix on a large simulation using the stochastic approximation expectation–maximization algorithm (SAEM). The expression of the Fisher information matrix for multiple responses is also evaluated by comparison with the empirical information obtained through a replicated simulation study using the first‐order linearization estimation methods implemented in the NONMEM software (first‐order (FO), first‐order conditional estimate (FOCE)) and the SAEM algorithm in the MONOLIX software. The predicted errors given by the approximated information matrix are close to those given by the information matrix obtained without linearization using SAEM and to the empirical ones obtained with FOCE and SAEM. The simulation study also illustrates the accuracy of both FOCE and SAEM estimation algorithms when jointly modelling multiple responses and the major limitations of the FO method. This study highlights the appropriateness of the approximated Fisher information matrix for multiple responses, which is implemented in PFIM 3.0, an extension of the R function PFIM dedicated to design evaluation and optimization. It also emphasizes the use of this computing tool for designing population multiple response studies, as for instance in PKPD studies or in PK studies including the modelling of the PK of a drug and its active metabolite. Copyright © 2009 John Wiley & Sons, Ltd.     

原位肛门整形重建术的研究

目的：探讨改进的内外括约肌在原位肛门整形重建术中的应用及其手术效果。方法：改进包括：①肛门内括约肌改进为双层双环肌套；②肛门外括约肌改进为股薄肌采用“围巾式”环绕结肠末端一周，其远端剖为两条，一条缝合固定于耻骨韧带；另一条缝合固定于骶尾韧带，即为肛门外括约肌重建和外括约肌浅部和深部的重建。结果：38例术后肛门外形及功能和远期生活质量、生存率均更为满意。术后随访总优良率达94．73％；远期生存率达76．32％。结论：低位直肠癌Miles术后，同时行改进的内外括约肌原位肛门整形重建的效果是可行的，更接近正常的肛门解剖结构和生理功能。     

Efficient high-frequency body coil for high-field MRI.

The use of body coils is favored for homogeneous excitation, and such coils are often paired with surface coils or arrays for sensitive reception in many MRI applications. While the body coil's physical size and resultant electrical length make this circuit difficult to design for any field strength, recent efforts to build efficient body coils for applications at 3T and above have been especially challenging. To meet this challenge, we developed an efficient new transverse electromagnetic (TEM) body coil and demonstrated its use in human studies at field strengths up to 4 T. Head, body, and breast images were acquired within peak power constraints of <8 kW. Bench studies indicate that these body coils are feasible to 8 T. RF shimming was used to remove a high-field-related cardiac imaging artifact in these preliminary studies. P41RR13230     

Acute encephalopathy associated with influenza and other viral infections

Acute encephalopathy is the most serious complication of pediatric viral infections, such as influenza and exanthem subitum. It occurs worldwide, but is most prevalent in East Asia, and every year several hundreds of Japanese children are affected by influenza-associated encephalopathy. Mortality has recently declined, but is still high. Many survivors are left with motor and intellectual disabilities, and some with epilepsy. This article reviews various syndromes of acute encephalopathy by classifying them into three major categories. The first group caused by metabolic derangement consists of various inherited metabolic disorders and the classical Reye syndrome. Salicylate is a risk factor of the latter condition. The second group, characterized by a systemic cytokine storm and vasogenic brain edema, includes Reye-like syndrome, hemorrhagic shock and encephalopathy syndrome, and acute necrotizing encephalopathy. Non-steroidal anti-inflammatory drugs, such as diclofenac sodium and mephenamic acid, may aggravate these syndromes. Severe cases are complicated by multiple organ failure and disseminated intravascular coagulation. Mortality is high, although methylprednisolone pulse therapy may be beneficial in some cases. The third group, characterized by localized edema of the cerebral cortex, has recently been termed acute encephalopathy with febrile convulsive status epilepticus, and includes hemiconvulsion-hemiplegia syndrome and acute infantile encephalopathy predominantly affecting the frontal lobes. Theophylline is a risk factor of these syndromes. The pathogenesis is yet to be clarified, but an increasing body of evidence points to excitotoxicity and delayed neuronal death.     

探究医院电子信息交换标准HL7

医药信息学在医学应用中的最大领域就是医院信息系统(Hospital Infornation System,HIS),随着HIS的快速发展,需要我们有一个开放的,统一的HIS开发和交换的标准.HL7是1987年开始发展起来的一个专门规范医疗机构用于临床信息,财务信息和管理信息电子信息交换的标准.它特别适合于解决不同厂商开发的医院信息系统、临床实验室系统及药学信息系统之间的互连问题.HL7在国内的发展刚刚起步,但是我国医疗卫生信息化发展很快,尤其是医疗保险、社区医疗和区域卫生信息系统等,都十分需要标准化的支持,HL7将成为建设这些系统的重要基础和关键技术.     

中医情志的发生机制刍议

在情志学说和脑主神明理论指导下对情志产生的生理机制作新的诠释。认为脑神的气化出入及整合作用是情志发生的生理基础 ;五脏所化的气血精津为情志发生的物质基础     

初次献血对红细胞膜Na+-K+-ATP酶活性的影响

目的探讨初次献血对红细胞膜Na+-K+-ATP酶活性的影响.方法应用比色法分别检测50例符合献血条件的健康初次献血者献血前后的红细胞膜Na+-K+-ATP酶活性,并对结果进行分析.结果初次献血者献血前后红细胞膜Na+-K+-ATP酶活性分别为3.121±0.441和2.907±0.397 μmol.Pi/107 RBC.h,两者比较无明显差异(P＞0.05).结论初次献血对红细胞膜Na+-K+-ATP酶活性无影响,献血不会造成红细胞功能损伤.     

冠心病危险因素与冠状动脉病变程度的相关性研究

目的:探讨冠心病危险因素与冠状动脉病变程度的关系.方法:选取150例冠心病患者行冠状动脉造影术及各项化验检查,冠状动脉病变程度以Gensini积分值表示,对冠心病危险因素和冠状动脉病变程度进行统计分析.结果:经多因素线性回归证实:非高密度脂蛋白胆固醇为冠状动脉病变程度的独立危险因素(P=0.030),而性别、年龄、空腹血糖、糖尿病、高血压、吸烟、家族史及甘油三酯、低密度脂蛋白胆固醇均与冠状动脉病变程度无明确相关.结论:非高密度脂蛋白胆固醇对冠状动脉病变严重程度具有重要的影响.     

加强学科建设提高中医儿科教学质量

中医儿科是河南省重点学科,加强学科管理,健全各项管理规章制度,科学合理设置儿科课程,实现理论与实践的结合,课堂与临床见习的结合;提高教师人文素质、教学水平,是保证儿科教学质量的关键.     

17β-雌二醇对子宫内膜异位症患者在位子宫内膜间质细胞β-catenin mRNA和蛋白表达的影响

目的研究17β-雌二醇(17β-E2)对子宫内膜异位症(内异症)患者在位子宫内膜间质细胞β-catenin mRNA和蛋白表达的影响,探讨Wnt/β-catenin信号通路在介导雌激素促进内异症发生发展的作用。方法体外分离培养内异症患者在位子宫内膜间质细胞。用不同浓度17β-E2处理子宫内膜间质细胞48 h;此后选用10-10mol/L 17β-E2处理子宫内膜间质细胞12、24和48 h,逆转录聚合酶链反应(RT-PCR)和免疫印迹法(Western blotting)检测17β-E2处理前后子宫内膜间质细胞β-catenin mRNA和蛋白的表达水平。同法分析雌激素受体拮抗剂ICI182,780(10-6mol/L)对17β-E2促进β-catenin mRNA和蛋白表达的影响。免疫组织化学染色观察17β-E2作用后β-catenin在子宫内膜间质细胞中的定位。结果17β-E2能明显促进内异症患者在位子宫内膜间质细胞β-catenin mRNA和蛋白的表达,并呈剂量和时间依赖性,于10-10mol/L作用48 h最明显。雌激素受体拮抗剂ICI182,780能明显抑制17β-E2对子宫内膜间质细胞β-catenin mRNA和蛋白的表达。免疫组织化学染色发现17β-E2能促进β-catenin在子宫内膜间质细胞核内的表达。结论雌激素可能通过激活Wnt/β-catenin信号通路促进内异症在位子宫内膜的异位种植。