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CombiTool—A New Computer Program for Analyzing Combination Experiments with Biologically Active Agents combitool -一种新的分析生物活性药物组合实验的计算机程序
Pub Date : 1999-04-01 DOI: 10.1006/cbmr.1999.1509
Valeska Dreβler, Gerhard Müller, Jürgen Sühnel

CombiTool is a new computer program for the analysis of combination effects of biologically active agents. It performs model calculations and an analysis of experimental combination effects for two or three agents according to both the Bliss independence and the Loewe additivity criteria. Zero interaction response surfaces are calculated from single-agent dose–response relations and compared to experimental combination data. The calculation of response surfaces for Loewe additivity is based on a new approach which combines the implicit definition equation in terms of doses alone with single-agent dose–response relations. The simultaneous analysis of experimental data according to both Loewe additivity and Bliss independence within one program can hopefully contribute to a better understanding of the meaning and limits of the two criteria. CombiTool has a built-in graphics facility which allows the direct visualization of the response surfaces or the corresponding contour plots and the experimental data.

CombiTool是一种新的用于分析生物活性药物联合效应的计算机程序。它根据Bliss独立性和Loewe可加性标准对两个或三个代理进行模型计算和实验组合效应分析。根据单剂剂量-响应关系计算出零相互作用响应面,并与实验组合数据进行了比较。Loewe可加性响应面的计算基于一种新的方法,该方法将单剂剂量的隐式定义方程与单剂剂量-反应关系相结合。根据Loewe可加性和Bliss独立性在一个程序中同时分析实验数据,有望有助于更好地理解这两个标准的含义和局限性。CombiTool有一个内置的图形工具,允许直接可视化响应面或相应的等高线图和实验数据。
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引用次数: 45
Using the Internet to Calculate Clinical Action Thresholds 使用互联网计算临床行动阈值
Pub Date : 1999-04-01 DOI: 10.1006/cbmr.1998.1505
Iztok Hozo , Benjamin Djulbegovic

Understanding the risks and benefits of available treatments represents an essential element of clinical practice. Previous work has demonstrated that knowledge of net benefits and net risks can relate to our decisions on whether or not to administer a particular treatment or order a diagnostic test. A wider application of this model has been difficult because data on net benefits and net risks are not directly reported. We used more frequently reported data on treatment efficacy (E) and risks (Rrx) to obtain an equation for the treatment threshold probability above which treatment should be given and below which it should be withheld. The diagnostic test should only be performed if the probability of a disease is between the testing threshold and the treatment threshold. We first described a theoretical background for these calculations. We then used a JavaScript programming language to write a computer program which physicians can use to calculate these threshold probabilities effortlessly through the Internet. In most clinical situations we do not have to achieve maximum diagnostic certainty in order to act. However, we should never treat or order a diagnostic test if the risk of the treatment is greater than its efficacy. The minimally requiredE/Rratio of a particular treatment is equal to the reciprocal value of the mortality/morbidity of untreated disease. Similarly, the lowest number of patients needed to be treated (NNT) for therapy to be worth administering is equal to the reciprocal of the treatment risk. We show how evidence-based summary measures of therapeutic effects, such as the treatment efficacy, harms, and NNT, can successfully be integrated within a decision analytic model. This in turn will facilitate wider use of the quantitative benefit–risk analysis. Accessing the Internet for direct and immediate approach to the formulas described here should make this task even easier in everyday clinical decision making.

了解现有治疗方法的风险和益处是临床实践的基本要素。先前的研究表明,对净收益和净风险的了解与我们是否进行特定治疗或要求进行诊断测试的决定有关。由于没有直接报告净收益和净风险的数据,这一模型很难得到更广泛的应用。我们使用了更频繁报道的关于治疗疗效(E)和风险(Rrx)的数据,以获得治疗阈值概率的方程,高于该概率应给予治疗,低于该概率应不予治疗。只有当疾病的概率介于检测阈值和治疗阈值之间时,才应进行诊断试验。我们首先描述了这些计算的理论背景。然后,我们使用JavaScript编程语言编写了一个计算机程序,医生可以通过互联网毫不费力地计算这些阈值概率。在大多数临床情况下,我们不必达到最大限度的诊断确定性才能采取行动。然而,如果治疗的风险大于其疗效,我们不应该治疗或订购诊断测试。特定治疗的最低要求de / r等于未经治疗的疾病的死亡率/发病率的倒数值。同样,治疗值得实施的最低患者数量(NNT)等于治疗风险的倒数。我们展示了治疗效果的循证总结措施,如治疗效果、危害和NNT,如何成功地整合到决策分析模型中。这反过来又将促进更广泛地使用定量的利益-风险分析。通过访问互联网,可以直接和即时地获得这里所描述的公式,这将使这项任务在日常临床决策中变得更加容易。
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引用次数: 14
Prediction of Blood Glucose Levels in Diabetic Patients Using a Hybrid AI Technique 使用混合人工智能技术预测糖尿病患者的血糖水平
Pub Date : 1999-04-01 DOI: 10.1006/cbmr.1998.1506
Jan John Liszka-Hackzell

One of the problems in the management of the diabetic patient is to balance the dose of insulin without exactly knowing how the patient's blood glucose concentration will respond. Being able to predict the blood glucose level would simplify the management. This paper describes an attempt to predict blood glucose levels using a hybrid AI technique combining the principal component method and neural networks. With this approach, no complicated models or algorithms need be considered. The results obtained from this fairly simple model show a correlation coefficient of 0.76 between the observed and the predicted values during the first 15 days of prediction. By using this technique, all the factors affecting this patient's blood glucose level are considered, since they are integrated in the data collected during this time period. It must be emphasized that the present method results in an individual model, valid for that particular patient under a limited period of time. However, the method itself has general validity, since the blood glucose variations over time have similar properties in any diabetic patient.

糖尿病患者管理中的一个问题是在不确切知道患者血糖浓度如何反应的情况下平衡胰岛素的剂量。能够预测血糖水平将简化管理。本文描述了一种结合主成分法和神经网络的混合人工智能技术来预测血糖水平的尝试。使用这种方法,不需要考虑复杂的模型或算法。从这个相当简单的模型中得到的结果显示,在预测的前15天,观测值与预测值之间的相关系数为0.76。通过使用该技术,所有影响该患者血糖水平的因素都被考虑在内,因为它们被整合在这段时间内收集的数据中。必须强调的是,本方法产生的是个体模型,在有限的时间内对该特定患者有效。然而,该方法本身具有普遍的有效性,因为血糖随时间的变化在任何糖尿病患者中都具有相似的特性。
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引用次数: 33
Implementation of Three-Dimensional EEG Brain Mapping 三维脑电图脑图的实现
Pub Date : 1999-04-01 DOI: 10.1006/cbmr.1998.1503
Tomi Heinonen , Antti Lahtinen , Veikko Häkkinen

The electroencephalogram (EEG) visualization software was developed containing two-dimensional (2D) and three-dimensional (3D) brain mapping modules. The input to the program is standard clinical individual patient data recorded using digital EEG and magnetic resonance imaging (MRI). The software utilizes several techniques, such as heuristic triangulation, ray casting, Gouraud shading, and image fusion to form multimodal 3D images. The program has been applied to the 3D visualization of various EEG signals, “cortical” EEG signals, and potential fields generated by a computer model. The developed program appears to operate efficiently and intuitively in PC/Windows environment.

开发了包含二维(2D)和三维(3D)脑图模块的脑电图(EEG)可视化软件。该程序的输入是使用数字脑电图和磁共振成像(MRI)记录的标准临床个体患者数据。该软件利用了几种技术,如启发式三角剖分、光线投射、Gouraud阴影和图像融合来形成多模态3D图像。该程序已应用于各种脑电图信号的三维可视化,“皮质”脑电图信号,以及由计算机模型产生的势场。所开发的程序在PC/Windows环境下运行高效、直观。
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引用次数: 14
PALIREL, a Computer Program for Analyzing Particle-to-Membrane Relations, with Emphasis on Electron Micrographs of Immunocytochemical Preparations and Gold Labeled Molecules PALIREL,一个用于分析粒子与膜关系的计算机程序,重点是免疫细胞化学制剂和金标记分子的电子显微图
Pub Date : 1999-04-01 DOI: 10.1006/cbmr.1999.1508
H.K. Ruud, T.W. Blackstad

Many vital substances, such as receptors, transporters, and ion channels, in cells occur associated with membranes. To an increasing extent their precise localization is demonstrated by immunocytochemical methods including labeling with gold particles followed by electron microscopy. PALIREL has primarily been developed to facilitate such research, enabling rapid analysis of topographic relations of particles (gold or others) to neighboring linear interfaces (membranes). After digitization of membranes and particles, the program particularly allows computation of (1) the particle number and number per unit length of membrane, in individual bins (membrane lengths) interactively defined along the membrane; (2) the distance of each particle from the membrane; (3) the particle number, and the density (number per μm2), in zones defined along (over and under) the membrane; and (4) the particle number and density in “zonebins” resulting from zones and bins being defined simultaneously. If there occurs, somewhere in the membrane, a segment of different nature, such as a synapse, the quantitative data may be had separately for that and the adjoining parts of the membrane. PALIREL allows interactive redefinition of bins, zones, or objects (particle-line files) while other definitions are retained. The results can be presented on the screen as tables and histograms and be printed on request. A dedicated graphic routine permits inspection on screen of lines, particles, zones, and bins. PALIREL is equally applicable to biological investigations of other kinds, in which the topographic relations of points (structures represented as points) to lines (boundaries) are to be examined. PALIREL is available from the authors on a noncommercial basis.

细胞中的许多重要物质,如受体、转运体和离子通道,都与细胞膜有关。在越来越多的程度上,它们的精确定位是通过免疫细胞化学方法证明,包括用金颗粒标记,然后是电子显微镜。PALIREL主要是为了促进这类研究而开发的,能够快速分析颗粒(金或其他)与邻近线性界面(膜)的地形关系。在对膜和颗粒进行数字化后,该程序特别允许计算(1)沿膜交互定义的单个容器(膜长度)中的颗粒数量和单位膜长度的数量;(2)各颗粒与膜的距离;(3)膜上、膜下区域内的颗粒数和密度(每μm2数);(4)同时定义分区和分区所产生的“分区箱”中的颗粒数和密度。如果在膜的某个地方,有一个不同性质的片段,比如突触,那么定量数据可能是单独的,它和膜的邻近部分是分开的。PALIREL允许在保留其他定义的同时交互式地重新定义箱子、区域或对象(粒子线文件)。结果可以在屏幕上以表格和直方图的形式显示,并可根据要求打印。一个专用的图形程序允许在屏幕上检查线、粒子、区域和箱。PALIREL同样适用于其他类型的生物调查,其中点(表示为点的结构)与线(边界)的地形关系将被检查。PALIREL在非商业的基础上可以从作者那里获得。
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引用次数: 17
Classification of Nasal Inspiratory Flow Shapes by Attributed Finite Automata 基于有限自动机的鼻吸气流形态分类
Pub Date : 1999-02-01 DOI: 10.1006/cbmr.1998.1499
T. Aittokallio , O. Nevalainen , U. Pursiheimo , T. Saaresranta , O. Polo

In a significant proportion of individuals, the physiologic decrease of muscle tone during sleep results in increased collapsibility of the upper respiratory airway. At peak inspiratory flow, the pharyngeal soft tissues may collapse and cause airflow limitation or even complete occlusion of the upper airway (sleep apnea). While there are plenty of methods to detect sleep apnea, only a few can be used to monitor flow limitation in sleeping individuals. Nasal prongs connected to pressure sensor provide information of the nasal airflow over time. This paper documents a method to automatically classify each nasal inspiratory pressure profile into one without flow limitation or six flow-limited ones. The recognition of the sample signals consists of three phases: preprocessing, primitive extraction, and word parsing phases. In the last one, a sequence of signal primitives is treated as a word and we test its membership in the attribute grammars constructed to the signal categories. The method gave in practical tests surprisingly high performance. Classifying 94;pc of the inspiratory profiles in agreement with the visual judgment of an expert physician, the performance of the method was considered good enough to warrant further testing in well-defined patient populations to determine the pressure profile distributions of different subject classes.

在很大比例的个体中,睡眠期间肌肉张力的生理性降低导致上呼吸道塌陷性增加。在吸气流量达到峰值时,咽部软组织可能塌陷,导致气流受限甚至完全阻塞上呼吸道(睡眠呼吸暂停)。虽然有很多方法可以检测睡眠呼吸暂停,但只有少数方法可以用于监测睡眠个体的血流限制。连接到压力传感器的鼻尖提供了鼻腔气流随时间变化的信息。本文提出了一种将每个鼻吸气压力剖面自动划分为一个无流量限制或六个流量限制的方法。样本信号的识别包括预处理、原语提取和词解析三个阶段。在最后一种方法中,将一系列信号原语视为一个词,并测试其在为信号类别构造的属性语法中的隶属性。该方法在实际测试中表现出惊人的高性能。根据专家医师的视觉判断,该方法的性能足够好,可以在明确定义的患者群体中进行进一步测试,以确定不同学科类别的压力分布。
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引用次数: 24
Design of a PC-Based System for Time-Domain and Spectral Analysis of Heart Rate Variability 基于pc的心率变异性时域和频谱分析系统的设计
Pub Date : 1999-02-01 DOI: 10.1006/cbmr.1998.1502
Holger G. Adelmann

Investigation of heart rate variability is the subject of considerable interest in physiology, clinical medicine, and clinical pharmacology. The functional assessment of the autonomic nerve system by observation of its main actors, the sympathetic and parasympathetic branch, is emphasizing the importance of autonomic regulation under different physiological circum stances, in several disease states, and under drug therapy. This paper describes a PC-based system designed with LabView that performs time-domain and frequency-domain analyses of heart rate variability as suggested by the guidelines of theEuropean Society of Cardiologyand theNorth American Society of Pacing and Electrophysiology.Examples for heart rate variability are given for different physiological states along with an analysis and evaluation by the system described.

心率变异性的研究是生理学、临床医学和临床药理学中相当感兴趣的课题。通过观察其主要参与者交感神经和副交感神经分支来评估自主神经系统的功能,强调了在不同生理情况下,在几种疾病状态下以及在药物治疗下自主神经调节的重要性。本文描述了用LabView设计的基于pc的系统,该系统根据欧洲心脏病学会和北美起搏和电生理学会的指导方针进行心率变异性的时域和频域分析。针对不同的生理状态给出了心率变异性的例子,并通过所描述的系统进行了分析和评估。
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引用次数: 15
The MISCAN-COLON Simulation Model for the Evaluation of Colorectal Cancer Screening MISCAN-COLON模拟模型评价结直肠癌筛查
Pub Date : 1999-02-01 DOI: 10.1006/cbmr.1998.1498
F. Loeve, R. Boer, G.J. van Oortmarssen, M. van Ballegooijen, J.D.F. Habbema

A general model for evaluation of colorectal cancer screening has been implemented in the microsimulation program MISCAN-COLON. A large number of fictitious individual life histories are simulated in each of which several colorectal lesions can emerge. Next, screening for colorectal cancer is simulated, which will change some of the life histories. The demographic characteristics, the epidemiology and natural history of the disease, and the characteristics of screening are defined in the input. All kinds of assumptions on the natural history of colorectal cancer and screening and surveillance strategies can easily be incorporated in the model. MISCAN-COLON gives detailed output of incidence, prevalence and mortality, and the results and effects of screening. It can be used to test hypotheses about the natural history of colorectal cancer, such as the duration of progressive adenomas, and screening characteristics, such as sensitivity of tests, against empirical data. In decision making about screening, the model can be used for evaluation of screening policies, and for choosing between competing policies by comparing their simulated incremental costs and effectiveness outcomes.

一个评估结直肠癌筛查的通用模型已经在微模拟程序MISCAN-COLON中实现。大量虚构的个人生活史被模拟在每个几个结直肠病变可以出现。接下来,模拟结肠直肠癌的筛查,这将改变一些生活史。在输入中定义了疾病的人口统计学特征、流行病学和自然历史以及筛查特征。关于结直肠癌的自然史以及筛查和监测策略的各种假设都可以很容易地纳入模型。MISCAN-COLON给出了发病率、患病率和死亡率的详细输出,以及筛查的结果和效果。它可以用来检验关于结肠直肠癌自然史的假设,如进展性腺瘤的持续时间,以及筛查特征,如测试的敏感性,与经验数据相对照。在筛选决策中,该模型可用于评估筛选政策,并通过比较其模拟的增量成本和有效性结果,在竞争政策之间进行选择。
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引用次数: 190
Similarity Measurement Method for the Classification of Architecturally Differentiated Images 建筑差异图像分类的相似性度量方法
Pub Date : 1999-02-01 DOI: 10.1006/cbmr.1998.1500
Yoav Smith , Gershom Zajicek , Michael Werman , Galina Pizov , Yoav Sherman

A similarity measurement method for the classification of architecturally differentiated image sections is described. The strength of the method is demonstrated by performing the complex task of assigning severity grading (Gleason grading) to histological slides of prostate cancer. As shown, all that is required to employ the method is a small set of preclassified images. The images can be real world images acquired by means of a camera, computer tomography, etc., or schematic drawings representing samples of different classes. The schematic option allows a quick test of the method for a particular classification problem.

本文描述了一种用于结构差分图像分段分类的相似性度量方法。通过对前列腺癌的组织学切片进行严重程度分级(Gleason分级)的复杂任务,证明了该方法的强度。如图所示,采用该方法所需要的只是一小组预分类图像。所述图像可以是通过照相机、计算机断层扫描等手段获得的真实世界图像,或者是表示不同类别样本的示意图。原理图选项允许对特定分类问题的方法进行快速测试。
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引用次数: 47
A Novel Algorithm for the Heart Rate Variability Analysis of Short-Term Recordings: Polar Representation of Respiratory Sinus Arrhythmia 短期记录心率变异性分析的新算法:呼吸性窦性心律失常的极坐标表示
Pub Date : 1999-02-01 DOI: 10.1006/cbmr.1998.1495
Pierre-Franois Migeotte, Yves Verbandt

A new method for the analysis of heart rate variability in short-term recordings is presented which consists of an analysis of the respiratory sinus arrhythmia in the time domain by means of a polar representation. Its main advantage is that it is applicable in experiments in which the respiration of the subject is not controlled. The algorithm is applied to data recorded on two astronauts during the Euromir-95 space mission. Statistical hypothesis tests demonstrate that the presence of a mouthpiece induces an increase of the respiratory sinus arrhythmia amplitude.

本文提出了一种分析短期心率变异性的新方法,该方法采用极坐标表示法对呼吸窦性心律失常进行时域分析。它的主要优点是适用于实验对象的呼吸不受控制的情况。该算法应用于两名宇航员在欧洲mir-95太空任务期间记录的数据。统计假设检验表明,呼吸口的存在引起呼吸窦性心律失常幅度的增加。
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引用次数: 13
期刊
Computers and biomedical research, an international journal
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