一种基于目录和关系的混合数据模型

目录和关系数据库分别在架构、安全、事务处理等方面各有优点,而许多信息管理系统,特别是互联网应用(电子商务、分布应用)系统中,既需要目录数据结构的与组织资源架构的一致性和分布特征,也需要关系数据对事务处理、数据挖掘的优势,两种数据结构的结合可以使系统数据更加结构化、应用开发更加高效、变更更加灵活.本文提出了一个基于LDAP/X500目录和SOL数据操作语言的关系数据库的混合数据模型框架,来解决一些具有组织结构、资源管理,又有事务处理、数据分析应用系统的数据框架问题.     

Improving Power by Dichotomizing (Even Under Normality)

This article reviews controversies surrounding dichotomization in biopharmaceutical research. Despite known loss of power following dichotomization in the univariate case, it is shown that dichotomizing continuous data can greatly improve the power of multiple testing procedures. To illustrate such gains, the apparently under-appreciated discrete multiple comparisons method is reviewed and applied to the case of dichotomization. The resulting method has precise control of the familywise error rate, and specific power gains relative to comparable methods that use the continuous data are demonstrated. Cases where such power gains are likely (even with normally distributed data) are identified, and applications to biopharmaceutical research are discussed. The first application is to gene expression analysis, where it is shown that power of classical multiple comparisons methods with normally distributed data (even false discovery rate controlling methods) can be arbitrarily low, while the dichotomized familywise error rate controlling method maintains a constant 0.92 power. A second application shows that multiple tests for endpoints in clinical trials can benefit by using dichotomization. Finally, in an analysis of multiple dichotomous thresholds to classify prostate cancer, it is shown that a discrete Boole inequality-based method can be quite powerful, even with highly correlated data.     

Size analysis of a pressurized metered dose inhaler-delivered suspension formulation by the API Aerosizer time-of-flight aerodynamic particle size analyzer.

Aerosizer time-of-flight (TOF) aerodynamic particle size analyzers (TSI-Amherst, Amherst, MA) are widely used for the rapid assessment of aerosols from a wide variety of drug delivery devices, including pressurized metered dose inhalers (pMDIs). This technique offers significant advantages in terms of rapid measurement times in comparison with the more time-consuming compendial methods such as the cascade impactor or multistage liquid impinger. Particle size analysis takes place by determining the TOF of individual particles following acceleration to supersonic velocity. No drug assay is performed; thus, the resulting size distribution also includes particles that do not contain any medication such as the excipients and surfactant that are present in most pMDI-based formulations. Illustrative data are presented for one particular formulation (Pulmicort: 200 micrograms of budesonide per dose; Astra Draco; Lund, Sweden) and demonstrate that bias from this source can significantly shift the reported particle distribution to finer sizes compared with impactor-based analysis in which direct assay for drug has taken place. In this case, the mass median aerodynamic diameter (MMAD) determined by an Aerosizer-LD was close to 2.4 microns, but was found to be approximately 4 microns using the cascade impactor-based procedure. Such a shift results in an overestimation of the fine particle fraction of the emitted dose, which may lead to misleading conclusions about the therapeutic benefit of a particular drug delivery system when making use of this formulation. TOF aerosol measurement techniques appear to be vulnerable to this type of bias for any suspension formulation in which the drug content is not homogeneously distributed within all particle sizes.     

人淋巴细胞转输SCID小鼠抗人脑胶质瘤特性分析

目的 探讨人外周血淋巴细胞转输给T和B淋巴细胞均先天性缺乏的SCID鼠后抗胶质瘤的免疫学特征。方法 采用APAAP、间接荧光原位杂交和流式细胞计数等检测转输在SCID鼠体内的人淋巴细胞分布、亚群变化和抗胶质瘤细胞毒活性。结果 尾静脉转输后CD3^ 、CD8^ 和HLA－Dr^ 等具有细胞毒活性细胞大部分分布在外周血和脾脏中,而腹腔转输者大部分在腹腔,这些细胞的功能维持1周时达高峰,在第2周下降时重复转输又可得到加强并具攻击肿瘤活性。结论 淋巴细胞免疫人化SCID模型是目前研究人胶质瘤免疫治疗的理想工具。     

One-way distribution system for water for injection: process management, microbiological quality control, and meeting regulatory requirements

The specifications for pharmaceutical water, the qualification and validation of water preparation facilities, strategies to prevent contamination by water-borne bacteria and lastly, the monitoring of microbiological purity are the topics of frequent seminars on Pharma Water Total Quality Management. The same subdivisions are used in the following paper on the process management and microbiological control of a one-way distribution system for Water for Injection. Since 1990, such a system has been in use in the production department of Pharma Hameln GmbH, a contract manufacturer of parenterals. Using this system as an example, the twin needs for flawless microbiological process control and for suitable measures to monitor water quality are discussed, which, together with extensive documentation of the qualification of the production and distribution system, ultimately led to acceptance of the system by regulatory authorities.     

Clinical Trials Do Not Use Random Samples Anymore

Current clinical trials do not use random samples, but, instead, convenience samples. This raises the risk of non-normal data.

The aim of this paper is to review and describe for a non-mathematical readership common methods for testing the normal property, as well as methods for analyzing the data in case of non-normality.

With slight departures from the normal distribution, normality tests can be used even so. They include, among other tests, the normal-, t-, chi-square- tests, analysis of variance, and regression analyses. They should not be used if the chi-square goodness of fit is significant. Rank-testing is, then, an alternative, but, sometimes, distributions do not allow for this approach either. This can be checked by the Kolmogorov-Smirnov test. If the latter test is also positive, rank-testing is not warranted, and confidence intervals can be derived from the data without prior assumption about the type of frequency distribution. This can be done by calculating the range within which 95% of all possible outcomes lie. Another popular method for this purpose is bootstrapping, which resamples at random from the study's own data. This paper reviews methods to assess data for compliance with normality, and summarizes solutions for the analysis of non-normal data. We strongly believe that normality statistics, although the mainstay of statistical analysis for centuries, will rapidly be replaced with non-normal testing as the awareness of non-normal sampling distributions grows, and we hope that the paper will strengthen this awareness and affect the design and analysis of future clinical trials.     

Managing the microbiological risks of drinking water

The microbiological contamination of drinking water supplies can have serious health consequences for consumers, and this has been dramatically illustrated in recent years by two disease outbreaks in Canada. In this paper, some factors that can influence the microbiological quality of drinking water and its management are examined. Frameworks have been proposed that help to clarify the main elements of health risk assessment and risk management, and, in accordance with these, risks can be logically characterized, evaluated and controlled. A protocol has been developed for microbiological risk assessment and a risk management framework now guides the development of Canada's national guidelines for drinking-water quality. Monitoring of indicator organisms and the application of adequate water treatment are the primary means recommended in the Canadian guidelines to safeguard health from the presence of water-borne pathogens. Understanding the biological characteristics of microbial pathogens is necessary for assessing their impact on community health and appraising the rationale behind drinking-water testing methods and their limitations. Improvements in health surveillance, monitoring, and risk characterization and application of concepts such as multiple barriers (source-to-tap) and total quality management should contribute to better management of the microbiological quality of drinking water.     

Microbiological and densitometric TLC analyses for peptides in liposomes

Quantitative determination of Leucinostatins and/or of similar peptides, such as Peptaibols, is sometimes quite difficult to perform especially when they are entrapped in vectors, i.e. liposomes, whose components display UV absorbances that may obscure those of the active principle. Therefore, in these cases, it is useful to find alternative ways, especially when high pressure liquid chromatography (HPLC) is difficult to perform or needs long procedure times. In the present paper, the use of microbiological and densitometric methods for quantitative analysis of Leucinostatin A (Leu-A) are described and the results compared with those from HPLC analyses. The use of microbiological and densitometric assays, furnished results comparable with those obtained by HPLC. Of the two methods used, the microbiological procedure appeared to be less accurate and precise.     

Statistical Methods for Conditional Survival Analysis

We investigate the survival distribution of the patients who have survived over a certain time period. This is called a conditional survival distribution. In this paper, we show that one-sample estimation, two-sample comparison and regression analysis of conditional survival distributions can be conducted using the regular methods for unconditional survival distributions that are provided by the standard statistical software, such as SAS and SPSS. We conduct extensive simulations to evaluate the finite sample property of these conditional survival analysis methods. We illustrate these methods with real clinical data.     

A method for normalizing drug responses to enhance reliability of parametric statistical tests

Experimental constraints often require that pharmacologists study the effects of treatments upon responses elicited with a single concentration of agonist. The choice of statistical analysis, nonparametric or parametric, will depend upon whether or not the responses are normally distributed. This study uses both Monte Carlo and theoretical approaches to examine the normality assumption as it applies to drug responses. Responses measured in systems where drug sensitivities follow a lognormal distribution are generally not normally distributed. A simple transformation of responses, however, can restore normality. Researchers may find it beneficial to transform response data prior to performing t tests, analysis of variance or other parametric statistics in order to preserve the power and confidence level of the test.     

A Mixture Distribution Approach to Assessing Medication Refill Compliance with Administrative Pharmacy Refill Records

The assessment of a patient’s medication compliance using pharmacy refill data is often challenging due to the complex distribution of the measures used to assess compliance. To address this problem, we propose a mixture distribution approach, with which methods based on the likelihood function, such as the likelihood ratio test, can be applied for testing intervention effects in randomized clinical trials. The advantage of a mixture distribution approach is that it allows for a flexible adaptation of censored data analysis to modeling refill data. It also supports visualization of the risk curve of noncompliance, conditional on given levels of refill compliance. Our approach is illustrated using pharmacy refill data from a prospective clinical trial.     

微生物检定法在抗生素质控分析中的应用

目的:分析微生物检定法在抗生素质控分析中的应用进展.方法:从抗生素的常量分析(抗生素成品及抗生素工业生产中间的质量控制)和微量分析(体内抗生素的分析一些物质中残留抗生素的分析)这两方面对微生素检定法的应用情况进行了论述.结果:微生物检定法在搞生素的含量测定中所占比例大幅度降低.结论:微生物检定法在抗生素的常量分析和微量分析中均是一种最常规的检测方法,但逐渐被高效液相色谱法取代已是发展趋势.     

Bacteriostatic versus bactericidal activity of ciprofloxacin in Escherichia coli assessed by flow cytometry using a novel far-red dye

As common microbiological methods for the assessment of bacteriostatic or bactericidal activities are very time-consuming, in this work we describe that the use of a novel far-red fluorescent stain, Vybrant DyeCycle Ruby (DCR) for the flow cytometric analysis of fluoroquinolone (ciprofloxacin) bacteriostatic and bactericidal activities in Escherichia coli proved to be specific for bacterial DNA and, after ciprofloxacin exposure, DNA distribution analysis was achieved using a 7.5?μM DCR concentration to stain 5 × 10? ethanol-fixed bacterial cells. The analysis of the bacterial DNA histograms obtained from the ciprofloxacin concentrations tested, enabled the distinction between ciprofloxacin bacteriostatic and bactericidal activities.     

环境分离菌在药品微生物检验中的应用

目的：讨论环境分离菌在药品微生物检验中的应用。方法：通过对各国药典、法规、指导原则、行业标准和行业指南等文件的梳理和分析,列出了环境分离菌在药品微生物检验中的应用建议和要求,并结合实例,进一步介绍了环境分离菌的应用范围。结果：各国药典和行业指南均要求或建议在消毒剂效能验证、抑菌效力检查、培养基方法适用性（培养基促生长试验）、检验方法的适用性、快速微生物检验方法和微生物检验替代方法验证等检验项目中增加使用环境分离菌（包括生产检验过程中人员、环境以及样品中分离菌）。结论：与标准菌株相比,环境分离菌更能够反映样品或环境实际存在微生物的情况,因此,在药品微生物检验中应用环境分离菌能够使检验结果对产品质量或环境做出更客观和科学的评价。可根据检验项目、药品的生产工艺和产品本身的特点,在风险评估的基础上选择适当的环境分离菌应用于检验过程中。     

Computerization of Ocular and Cutaneous Toxicological Data

Methods available for the computerization of research data depend heavily on professional programming using main frame systems.^1,2 Systems described for microcomputers depend on intensive programming languages such as PASCAL³ or BASIC⁴ for their system needs. This paper describes application of an “off-the-shelf” software package for the management of ocular and cutaneous toxicology data on consumer products.

Before a consumer product is available commercially, a solid history of chemical, microbiological, physical, and toxicological data has been generated. These data are a valuable product substantiation tool and must, therefore, be maintained in permanent files as part of a product's history. Over 46 years of support data have been generated in our department. The task of manually accessing the information was formidable and the size of the system itself precluded detailed data analysis or manipulation. Computerization of the data presented the best way to continue using the data and expand its application.     

Detecting phase separation of freeze-dried binary amorphous systems using pair-wise distribution function and multivariate data analysis

The purpose of this study is to investigate the use of multivariate data analysis for powder X-ray diffraction-pair-wise distribution function (PXRD-PDF) data to detect phase separation in freeze-dried binary amorphous systems. Polymer–polymer and polymer–sugar binary systems at various ratios were freeze-dried. All samples were analyzed by PXRD, transformed to PDF and analyzed by principal component analysis (PCA). These results were validated by differential scanning calorimetry (DSC) through characterization of glass transition of the maximally freeze-concentrate solute (T_g’). Analysis of PXRD-PDF data using PCA provides a more clear ‘miscible’ or ‘phase separated’ interpretation through the distribution pattern of samples on a score plot presentation compared to residual plot method. In a phase separated system, samples were found to be evenly distributed around the theoretical PDF profile. For systems that were miscible, a clear deviation of samples away from the theoretical PDF profile was observed. Moreover, PCA analysis allows simultaneous analysis of replicate samples. Comparatively, the phase behavior analysis from PXRD-PDF-PCA method was in agreement with the DSC results. Overall, the combined PXRD-PDF-PCA approach improves the clarity of the PXRD-PDF results and can be used as an alternative explorative data analytical tool in detecting phase separation in freeze-dried binary amorphous systems.     

《中国药典》微生物鉴定相关标准体系建立的回顾及展望

微生物污染在制剂、原辅料以及生产环境中具有分布不均匀、控制难度大等特点,控制不得当会严重影响着产品质量和用药安全。微生物鉴定在微生物的检验和控制工作中尤为重要,只有对微生物进行了适宜的鉴定,才能满足药品质量控制、偏差调查和溯源分析的需要,进而实现对药品的全生命周期质量控制。本综述全面回顾了《中国药典》收载的与微生物鉴定相关标准内容和检验方法,对比国外药典微生物鉴定相关部分标准要求,同时对《中国药典》微生物鉴定相关未来发展方向进行了展望,旨在为药品相关微生物检验工作提供信息,同时也为今后药典增修订相关通则及指导原则提供借鉴和参考。     

A simple method for optimising transformation of non‐parametric data: an illustration by reference to cortisol assays

Neuroendocrine data are typically positively skewed and rarely conform to the expectations of a Gaussian distribution. This can be a problem when attempting to analyse results within the framework of the general linear model, which relies on assumptions that residuals in the data are normally distributed. One frequently used method for handling violations of this assumption is to transform variables to bring residuals into closer alignment with assumptions (as residuals are not directly manipulated). This is often attempted through ad hoc traditional transformations such as square root, log and inverse. However, Box and Cox (Box & Cox, 1964 ) observed that these are all special cases of power transformations and proposed a more flexible method of transformation for researchers to optimise alignment with assumptions. The goal of this paper is to demonstrate the benefits of the infinitely flexible Box–Cox transformation on neuroendocrine data using syntax in spss . When applied to positively skewed data typical of neuroendocrine data, the majority (~2/3) of cases were brought into strict alignment with Gaussian distribution (i.e. a non‐significant Shapiro–Wilks test). Those unable to meet this challenge showed substantial improvement in distributional properties. The biggest challenge was distributions with a high ratio of kurtosis to skewness. We discuss how these cases might be handled, and we highlight some of the broader issues associated with transformation. Copyright © 2016 John Wiley & Sons, Ltd.     

Competitive Workflow: novel software architecture for automating drug design

As industrialization of laboratory processes for drug discovery continues to gather momentum, the bottleneck has moved toward exploitation of this tide of information to enable better quality decisions. The development of information-management systems to automate data and materials management can have a positive impact on productivity, as can increasingly sophisticated computer-aided molecular design approaches. However, as long as key decisions can only be taken by a small number of expert individuals working in a complex social environment, the impact of such innovations will be limited. This review describes Competitive Workflow, a distributed multi-agent system explicitly designed for the automation of decision making, currently the preserve of the expert. The approach builds on workflow architectures that capture best practice in information processing, but aims to extend these to model the tacit knowledge of the expert in the selection of alternative pathways through the workflow. The review also discusses recent developments in related workflow-management systems, particularly for information management and processing services front multiple sources, as well as distributed multi-agent approaches. A specific implementation of Competitive workflow--the Discovery Bus--and its application to meta-quantitative structure-activity relationship analysis is also described.     

Liquid chromatography for the quantitative analysis of antibiotics—some applications using poly(styrenedivinylbenzene)

Problems arising from the microbiological assay of antibiotics are discussed. The existence of several systems to express the potency leads to confusion. The use of potency to express the content of bulk products can lead to difficulties in the interpretation of the content of pharmaceutical preparations. Such problems can be avoided if the content of antibiotics is expressed as percentage weight in weight. This involves the application of selective assay methods such as liquid chromatography. The reproducibility of liquid chromatography depends largely on the quality of the stationary phase. Use of poly(styrene-divinylbenzene) as the stationary phase can lead to good reproducibility as is reported for erythromycin and for the tetracyclines, of which minocycline is discussed as an example.