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In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. 体内验证的生物信息学为基础的工具,以确定降低复制能力的HIV-1。
Pub Date : 2010-01-01 Epub Date: 2010-12-03 DOI: 10.2174/1874431101004010225
Christina M R Kitchen, Paul Krogstad, Scott G Kitchen

Although antiretroviral drug resistance is common in treated HIV infected individuals, it is not a consistent indicator of HIV morbidity and mortality. To the contrary, HIV resistance-associated mutations may lead to changes in viral fitness that are beneficial to infected individuals. Using a bioinformatics-based model to assess the effects of numerous drug resistance mutations, we determined that the D30N mutation in HIV-1 protease had the largest decrease in replication capacity among known protease resistance mutations. To test this in silico result in an in vivo environment, we constructed several drug-resistant mutant HIV-1 strains and compared their relative fitness utilizing the SCID-hu mouse model. We found HIV-1 containing the D30N mutation had a significant defect in vivo, showing impaired replication kinetics and a decreased ability to deplete CD4+ thymocytes, compared to the wild-type or virus without the D30N mutation. In comparison, virus containing the M184V mutation in reverse transcriptase, which shows decreased replication capacity in vitro, did not have an effect on viral fitness in vivo. Thus, in this study we have verified an in silico bioinformatics result with a biological assessment to identify a unique mutation in HIV-1 that has a significant fitness defect in vivo.

尽管抗逆转录病毒药物耐药性在接受治疗的艾滋病毒感染者中很常见,但它并不是艾滋病毒发病率和死亡率的一致指标。相反,与HIV耐药性相关的突变可能会导致病毒适应度的变化,这对感染者有利。使用基于生物信息学的模型来评估许多耐药性突变的影响,我们确定HIV-1蛋白酶中的D30N突变在已知蛋白酶耐药性突变中复制能力下降幅度最大。为了在体内环境中测试这一结果,我们构建了几种耐药突变HIV-1菌株,并利用SCID-hu小鼠模型比较了它们的相对适应度。我们发现,与没有D30N突变的野生型或病毒相比,含有D30N变异的HIV-1在体内具有显著缺陷,表现出复制动力学受损和消耗CD4+胸腺细胞的能力下降。相比之下,逆转录酶中含有M184V突变的病毒在体外表现出复制能力下降,但在体内对病毒适应度没有影响。因此,在这项研究中,我们通过生物评估验证了计算机生物信息学结果,以确定HIV-1中一种在体内具有显著适应度缺陷的独特突变。
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引用次数: 0
DISTq: An Iterative Analysis of Glucose Data for Low-Cost, Real-Time and Accurate Estimation of Insulin Sensitivity. DISTq:低成本、实时、准确估计胰岛素敏感性的葡萄糖数据迭代分析。
Pub Date : 2009-12-02 DOI: 10.2174/1874431100903010065
Paul D Docherty, J Geoffrey Chase, Thomas Lotz, Christopher E Hann, Geoffrey M Shaw, Juliet E Berkeley, J I Mann, Kirsten McAuley

Insulin sensitivity (SI) estimation has numerous uses in medical and clinical situations. However, highresolution tests that are useful for clinical diagnosis and monitoring are often too intensive, long and costly for regular use. Simpler tests that mitigate these issues are not accurate enough for many clinical diagnostic or monitoring scenarios. The gap between these tests presents an opportunity for new approaches. The quick dynamic insulin sensitivity test (DISTq) utilises the model-based DIST test protocol and a series of population estimates to eliminate the need for insulin or C-peptide assays to enable a high resolution, low-intensity, real-time evaluation of SI. The method predicts patient specific insulin responses to the DIST test protocol with enough accuracy to yield a useful clinical insulin sensitivity metric for monitoring of diabetes therapy. The DISTq method replicated the findings of the fully sampled DIST test without the use of insulin or C-peptide assays. Correlations of the resulting SI values was R=0.91. The method was also compared to the euglycaemic hyperinsulinaemic clamp (EIC) in an in-silico Monte-Carlo analysis and showed a good ability to re-evaluate SI(EIC) (R=0.89), compared to the fully sampled DIST (R=0.98) Population-derived parameter estimates using a-posteriori population-based functions derived from DIST test data enables the simulation of insulin profiles that are sufficiently accurate to estimate SI to a relatively high precision. Thus, costly insulin and C-peptide assays are not necessary to obtain an accurate, but inexpensive, real-time estimate of insulin sensitivity. This estimate has enough resolution for SI prediction and monitoring of response to therapy. In borderline cases, re-evaluation of stored (frozen) blood samples for insulin and C-peptide would enable greater accuracy where necessary, enabling a hierarchy of tests in an economical fashion.

胰岛素敏感性(SI)估计在医学和临床情况下有许多用途。然而,对临床诊断和监测有用的高分辨率测试往往过于密集、耗时和昂贵,无法经常使用。减轻这些问题的简单测试对于许多临床诊断或监测场景来说不够准确。这些测试之间的差距为新方法提供了机会。快速动态胰岛素敏感性测试(DISTq)利用基于模型的DIST测试方案和一系列人群估计来消除对胰岛素或c肽检测的需要,从而实现高分辨率、低强度、实时的SI评估。该方法预测患者对DIST测试方案的特异性胰岛素反应,准确度足以为监测糖尿病治疗提供有用的临床胰岛素敏感性指标。DISTq方法在不使用胰岛素或c肽测定的情况下复制了完全抽样DIST测试的结果。所得SI值的相关性R=0.91。该方法还与蒙特卡罗计算机分析中的血糖高胰岛素钳(EIC)进行了比较,与完全采样的DIST (R=0.98)相比,显示出良好的重新评估SI(EIC)的能力(R=0.89)。使用基于DIST测试数据的后验群体函数的人群衍生参数估计可以模拟胰岛素谱,足够准确地估计SI到相对较高的精度。因此,昂贵的胰岛素和c肽检测对于获得准确、廉价、实时的胰岛素敏感性评估是没有必要的。这一估计对于SI的预测和治疗反应的监测具有足够的分辨率。在临界情况下,重新评估储存(冷冻)血液样本的胰岛素和c肽,在必要时可以提高准确性,从而以经济的方式进行分层测试。
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引用次数: 48
Analysis of Clinical Record Data for Anticoagulation Management within an EHR System. 分析电子病历系统中用于抗凝管理的临床记录数据。
Pub Date : 2009-08-19 DOI: 10.2174/1874431100903010054
T Austin, D Kalra, N C Lea, D L H Patterson, D Ingram

Objectives: This paper reports an evaluation of the properties of a generic electronic health record information model that were actually required and used when importing an existing clinical application into a generic EHR repository.

Method: A generic EHR repository and system were developed as part of the EU Projects Synapses and SynEx. A Web application to support the management of anticoagulation therapy was developed to interface to the EHR system, and deployed within a north London hospital with five years of cumulative clinical data from the previous existing anticoagulation management application. This offered the opportunity to critique those parts of the generic EHR that were actually needed to represent the legacy data.

Results: The anticoagulation records from 3,226 patients were imported and represented using over 900,000 Record Components (i.e. each patient's record contained on average 289 nodes), of which around two thirds were Element Items (i.e. value-containing leaf nodes), the remainder being container nodes (i.e. headings and sub-headings). Each node is capable of incorporating a rich set of context properties, but in reality it was found that many properties were not used at all, and some infrequently (e.g. only around 0.5% of Record Components had ever been revised).

Conclusions: The process of developing generic EHR information models, arising from research and embodied within new-generation interoperability standards and specifications, has been strongly driven by requirements. These requirements have been gathered primarily by collecting use cases and examples from clinical communities, and been added to successive generations of these models. A priority setting approach has not to date been pursued - all requirements have been received and almost invariably met. This work has shown how little of the resulting model is actually needed to represent useful and usable clinical data. A wider range of such evaluations, looking at different kinds of existing clinical system, is needed to balance the theoretical requirements gathering processes, in order to result in EHR information models of an ideal level of complexity.

目的:本文报告了对通用电子健康记录信息模型属性的评估:本文报告了对通用电子健康记录信息模型属性的评估,这些属性是在将现有临床应用程序导入通用电子健康记录存储库时实际需要和使用的:方法:作为欧盟项目 Synapses 和 SynEx 的一部分,开发了通用电子病历库和系统。开发了一个支持抗凝疗法管理的网络应用程序,与电子病历系统相连接,并在伦敦北部的一家医院内部署,其中包含了之前现有抗凝管理应用程序中累积的五年临床数据。这提供了一个机会,可以对通用电子病历中实际需要用来表示遗留数据的部分进行批判:导入了 3,226 名患者的抗凝记录,并使用超过 900,000 个记录组件(即每名患者的记录平均包含 289 个节点)来表示,其中约三分之二为元素项(即含数值的叶节点),其余为容器节点(即标题和副标题)。每个节点都能包含丰富的上下文属性,但在现实中,我们发现许多属性根本没有被使用过,有些甚至很少被使用(例如,只有约 0.5% 的记录组件被修改过):结论:开发通用电子病历信息模型的过程主要是由需求驱动的,这些需求来自研究,并体现在新一代互操作性标准和规范中。这些需求主要是通过从临床社区收集用例和实例收集而来,并被添加到这些模型的历代版本中。迄今为止,我们还没有采用确定优先级的方法--所有的要求都已收到,而且几乎无一例外地得到了满足。这项工作表明,所产生的模型实际上只需要很少的内容就能代表有用和可用的临床数据。为了平衡理论上的需求收集过程,需要对不同类型的现有临床系统进行更广泛的此类评估,以产生具有理想复杂程度的电子病历信息模型。
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引用次数: 0
New Application of IEEE 11073 to Home Health Care. IEEE 11073在家庭保健中的新应用
Pub Date : 2009-06-26 DOI: 10.2174/1874431100903010044
Isao Mizukura, Toshiyo Tamura, Yutaka Kimura, Wenwei Yu

We propose a new home health care network for the acquisition and transmission of data from ordinary home health care appliances based on IEEE11073. In this study, we develop a standard protocol for data collection and a simple interface to accommodate different monitoring systems that make use of different data protocols. The system provides for one-way data transmission, thus saving power and conforming to Japanese pharmaceutical law. Our standardized protocol was verified during a 1-year field test involving 20 households in Japan. Data transmission errors between home health care devices and the home gateway were 4.21 per a day with our newly developed standard protocol. Over a 1 year period, we collected and analyzed data from 241,000 separate sources associated with healthy, home-based patients and chronically ill, clinic-based patients, the latter through physician intervention. We evaluate some of the possible applications for collecting daily health care data and introduce some of our findings relating primarily to body weight and blood pressure monitoring for elderly subjects in their own homes.

我们提出了一种基于IEEE11073的新型家庭医疗网络,用于采集和传输来自普通家庭医疗设备的数据。在本研究中,我们开发了一个数据收集的标准协议和一个简单的接口,以适应使用不同数据协议的不同监控系统。该系统提供单向数据传输,从而节省电力并符合日本制药法。我们的标准化方案在日本20个家庭为期1年的现场测试中得到了验证。使用我们新开发的标准协议,家庭医疗保健设备与家庭网关之间的数据传输错误为每天4.21次。在1年的时间里,我们收集并分析了来自241,000个独立来源的数据,这些数据与健康的居家患者和慢性病患者相关,后者通过医生干预。我们评估了收集日常医疗保健数据的一些可能的应用,并介绍了我们的一些主要与老年人在自己家中监测体重和血压有关的发现。
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引用次数: 16
Classification of event-related potentials associated with response errors in actors and observers based on autoregressive modeling. 基于自回归模型的行为者和观察者反应误差相关电位分类。
Pub Date : 2009-05-15 DOI: 10.2174/1874431100903010032
Christos E Vasios, Errikos M Ventouras, George K Matsopoulos, Irene Karanasiou, Pantelis Asvestas, Nikolaos K Uzunoglu, Hein T Van Schie, Ellen R A de Bruijn

Event-Related Potentials (ERPs) provide non-invasive measurements of the electrical activity on the scalp related to the processing of stimuli and preparation of responses by the brain. In this paper an ERP-signal classification method is proposed for discriminating between ERPs of correct and incorrect responses of actors and of observers seeing an actor making such responses. The classification method targeted signals containing error-related negativity (ERN) and error positivity (Pe) components, which are typically associated with error processing in the human brain. Feature extraction consisted of Multivariate Autoregressive modeling combined with the Simulated Annealing technique. The resulting information was subsequently classified by means of an Artificial Neural Network (ANN) using back-propagation algorithm under the "leave-one-out cross-validation" scenario and the Fuzzy C-Means (FCM) algorithm. The ANN consisted of a multi-layer perceptron (MLP). The approach yielded classification rates of up to 85%, both for the actors' correct and incorrect responses and the corresponding ERPs of the observers. The electrodes needed for such classifications were situated mainly at central and frontal areas. Results provide indications that the classification of the ERN is achievable. Furthermore, the availability of the Pe signals, in addition to the ERN, improves the classification, and this is more pronounced for observers' signals. The proposed ERP-signal classification method provides a promising tool to study error detection and observational-learning mechanisms in performance monitoring and joint-action research, in both healthy and patient populations.

事件相关电位(ERPs)提供了与大脑处理刺激和准备反应相关的头皮电活动的非侵入性测量。本文提出了一种erp信号分类方法,用于区分行为者正确和错误反应的erp信号以及观察者看到行为者做出正确和错误反应的erp信号。该分类方法针对的是包含错误相关负性(ERN)和错误正性(Pe)成分的信号,这些成分通常与人脑中的错误处理有关。特征提取由多元自回归建模和模拟退火技术相结合组成。结果信息随后通过人工神经网络(ANN)在“留一交叉验证”场景下使用反向传播算法和模糊c均值(FCM)算法进行分类。该人工神经网络由多层感知器(MLP)组成。该方法产生了高达85%的分类率,无论是演员的正确和不正确的反应,还是观察者相应的erp。这种分类所需的电极主要位于中央和额叶区。结果表明ERN的分类是可以实现的。此外,除了ERN之外,Pe信号的可用性也改善了分类,这对于观察者的信号来说更为明显。提出的erp信号分类方法为健康人群和患者群体的绩效监测和联合行动研究中的错误检测和观察学习机制研究提供了一个有前途的工具。
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引用次数: 8
The check your cannabis screener: a new online personalized feedback tool. 检查你的大麻筛选器:一个新的在线个性化反馈工具。
Pub Date : 2009-05-07 DOI: 10.2174/1874431100903010027
John A Cunningham, Trevor van Mierlo

This brief report describes the development and first year of use of an Internet-based screener for Cannabis users. Two versions of the Check Your Cannabis screener were compared, one linked to an already established harm reduction website for young Cannabis users (as an exercise called "Check how I compare with others," on www.WhatsWithWeed.ca) and the other a standalone version (www.CheckYourCannabis.net). The What's With Weed version attracted ten times more users and had a significantly younger audience as compared to the standalone version, underlining the benefits of targeting a website to a specific audience and linking to websites with already established reputations. Further work is needed to establish any impact on actual Cannabis use from taking the Check Your Cannabis screener.

这份简短的报告描述了基于互联网的大麻使用者筛选器的发展和第一年的使用情况。我们比较了两个版本的“检查你的大麻”筛选器,其中一个链接到一个已经建立的针对年轻大麻使用者的危害减少网站(在www.WhatsWithWeed.ca上作为一项名为“检查我与他人的比较”的练习),另一个是独立版本(www.CheckYourCannabis.net)。与独立版本相比,What's With Weed版本吸引了10倍多的用户,并且拥有更年轻的用户,这突显了针对特定用户的网站以及链接到已建立声誉的网站的好处。需要进一步的工作来确定采取检查您的大麻筛选器对实际大麻使用的任何影响。
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引用次数: 13
Quantitative texture analysis and transesophageal echocardiography to characterize the acute myocardial contusion. 定量肌理分析及经食管超声心动图表征急性心肌挫伤。
Pub Date : 2009-04-21 DOI: 10.2174/1874431100903010013
Abdelaziz Amichi, Pascal Laugier

Myocardial contusion (MC) is a common injury following blunt chest trauma without any specific symptoms.Several techniques such as electrocardiogram, estimation of myocardial band fraction of creatine phosphokinase, chest radiography and the scintiscanning missed efficiency to characterize the MC.Another technique based on transesophageal echocardiography [TEE] allows to visualize the structures of the heart with a good spatial resolution.We postulated that the quantitative texture analysis of regional image texture in two- dimensional [2D] TEE echocardiograms would be an accurate method to differentiate normal from abnormal myocardial wall.This preliminary experimental study demonstrated the feasibility of the proposed technique.

心肌挫伤(MC)是钝性胸部外伤后常见的损伤,无特殊症状。一些技术,如心电图、肌酸磷酸激酶心肌带分数的估计、胸片和科学扫描,都不能有效地表征mc。另一种基于经食管超声心动图(TEE)的技术可以以良好的空间分辨率可视化心脏结构。我们认为对二维TEE超声心动图区域图像纹理的定量纹理分析将是一种准确区分正常与异常心肌壁的方法。初步的实验研究证明了该技术的可行性。
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引用次数: 5
Parametric analysis of orthopedic screws in relation to bone density. 骨科螺钉与骨密度关系的参数分析。
Pub Date : 2009-04-21 DOI: 10.2174/1874431100903010019
Elisabetta M Zanetti, Massimiliano Salaorno, Giovanni Grasso, Alberto L Audenino

A global study of geometry and material properties of orthopedic screws was performed, considering not only the effect of each single factor (screw pitch, number of threads, fillet angle, etc.) but also their interactions with respect to bone density.The stress patterns resulting from different screw geometries and bone densities were analyzed using finite element techniques, taking into account different levels of osseointegration between the screw and the bone. These numerical models where validated through experimental pull-out tests, where a pull out force of 120 N produced localized failure of the last thread (stresses above 0.42 MPa). The results of the numerical simulations were then summarised using a multi-factorial parametric analysis. This demonstrated the great relevance of the interaction between bone density and screw pitch, showing that the optimal screw pitch can vary by more than 25% for different densities (0.35 g/cm(3) and 0.47 g/cm(3), respectively).The parameters calculated by means of the multi-factorial analysis allow the pull out force to be estimated for different osseointegration levels, different screw geometries and material properties, and for different bone densities. The final objective is to determine the best choice of implant for each individual patient.

对骨科螺钉的几何和材料特性进行了全面研究,不仅考虑了每个单一因素(螺钉节距、螺纹数、圆角等)的影响,还考虑了它们与骨密度的相互作用。考虑到螺钉与骨之间不同程度的骨整合,使用有限元技术分析了不同螺钉几何形状和骨密度产生的应力模式。这些数值模型通过实验拉出测试进行了验证,其中120 N的拉出力导致最后一根螺纹局部失效(应力大于0.42 MPa)。数值模拟的结果,然后总结使用多因子参数分析。这表明骨密度和螺钉间距之间的相互作用具有很大的相关性,表明不同密度下的最佳螺钉间距可相差25%以上(分别为0.35 g/cm(3)和0.47 g/cm(3))。通过多因素分析计算出的参数可以估计不同骨整合水平、不同螺钉几何形状和材料特性以及不同骨密度下的拔出力。最终目标是为每个患者确定最佳的种植体选择。
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引用次数: 11
Do hummingbirds see in ultraviolet? 蜂鸟能看见紫外线吗?
Pub Date : 2009-04-02 DOI: 10.2174/1874431100903010009
M Curé, A G Palacios

We present a numerical model to fit the electroretinogram (ERG), a gross evoked eye visual potential, that originate in the retina through photons absorption by photoreceptors and then involve the contribution form others retinal neurons. We use the ERG measured in a hummingbird, to evaluate the most likely retinal mechanism - cones visual pigments and oil-droplets - that participate in their high dimensional tetra or pentachromatic color hyperspace. The model - a nonlinear fit - appears to be a very useful tool to predict the underlying contribution visual mechanism for a variety of retinal preparation.

我们提出了一个适合视网膜电图(ERG)的数值模型,ERG是一种总诱发眼视觉电位,它起源于视网膜,通过光感受器吸收光子,然后涉及其他视网膜神经元的贡献。我们使用在蜂鸟身上测量的ERG来评估最可能的视网膜机制——视锥视色素和油滴——它们参与了高维四色或五色超空间。该模型-一个非线性拟合-似乎是一个非常有用的工具,以预测潜在的贡献视觉机制的各种视网膜的准备。
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引用次数: 2
Cardiac health diagnosis using higher order spectra and support vector machine. 基于高阶谱和支持向量机的心脏健康诊断。
Pub Date : 2009-02-26 DOI: 10.2174/1874431100903010001
Chua Kuang Chua, Vinod Chandran, Rajendra U Acharya, Lim Choo Min

The Electrocardiogram (ECG) is an important bio-signal representing the sum total of millions of cardiac cell depolarization potentials. It contains important insight into the state of health and nature of the disease afflicting the heart. Heart rate variability (HRV) refers to the regulation of the sinoatrial node, the natural pacemaker of the heart by the sympathetic and parasympathetic branches of the autonomic nervous system. The HRV signal can be used as a base signal to observe the heart's functioning. These signals are non-linear and non-stationary in nature. So, higher order spectral (HOS) analysis, which is more suitable for non-linear systems and is robust to noise, was used. An automated intelligent system for the identification of cardiac health is very useful in healthcare technology. In this work, we have extracted seven features from the heart rate signals using HOS and fed them to a support vector machine (SVM) for classification. Our performance evaluation protocol uses 330 subjects consisting of five different kinds of cardiac disease conditions. We demonstrate a sensitivity of 90% for the classifier with a specificity of 87.93%. Our system is ready to run on larger data sets.

心电图(ECG)是一种重要的生物信号,代表了数百万个心脏细胞去极化电位的总和。它包含了对健康状况和折磨心脏的疾病性质的重要见解。心率变异性(HRV)是指自主神经系统交感神经和副交感神经分支对窦房结的调节,窦房结是心脏的天然起搏器。心率波动信号可以作为观察心脏功能的基础信号。这些信号本质上是非线性和非平稳的。因此,采用了更适合非线性系统且对噪声具有鲁棒性的高阶谱分析方法。心脏健康的自动智能识别系统在医疗保健技术中是非常有用的。在这项工作中,我们使用HOS从心率信号中提取了7个特征,并将它们输入到支持向量机(SVM)中进行分类。我们的绩效评估方案使用了330名受试者,包括五种不同的心脏疾病。我们证明该分类器的灵敏度为90%,特异性为87.93%。我们的系统可以在更大的数据集上运行。
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引用次数: 51
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The open medical informatics journal
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