• 【关于过分散计数数据的EM算法。】 复制标题 收藏 收藏
    DOI:10.1177/096228029700600106 复制DOI
    作者列表:McLachlan GJ
    BACKGROUND & AIMS: In this paper, we consider the use of the EM algorithm for the fitting of distributions by maximum likelihood to overdispersed count data. In the course of this, we also provide a review of various approaches that have been proposed for the analysis of such data. As the Poisson and binomial regression models, which are often adopted in the first instance for these analyses, are particular examples of a generalized linear model (GLM), the focus of the account is on the modifications and extensions to GLMs for the handling of overdispersed count data.

    背景与目标: 在本文中,我们考虑使用EM算法通过最大似然对过度分散的计数数据进行分布拟合。在此过程中,我们还对已提出的用于分析此类数据的各种方法进行了回顾。由于通常在这些分析中首先采用的泊松和二项式回归模型是广义线性模型 (GLM) 的特殊示例,因此该帐户的重点是对GLM的修改和扩展,以处理过度分散的计数数据。
  • 【临床试验中的缺失数据: 基于控制的均值归因和敏感性分析。】 复制标题 收藏 收藏
    DOI:10.1002/pst.1817 复制DOI
    作者列表:Mehrotra DV,Liu F,Permutt T
    BACKGROUND & AIMS: :In some randomized (drug versus placebo) clinical trials, the estimand of interest is the between-treatment difference in population means of a clinical endpoint that is free from the confounding effects of "rescue" medication (e.g., HbA1c change from baseline at 24 weeks that would be observed without rescue medication regardless of whether or when the assigned treatment was discontinued). In such settings, a missing data problem arises if some patients prematurely discontinue from the trial or initiate rescue medication while in the trial, the latter necessitating the discarding of post-rescue data. We caution that the commonly used mixed-effects model repeated measures analysis with the embedded missing at random assumption can deliver an exaggerated estimate of the aforementioned estimand of interest. This happens, in part, due to implicit imputation of an overly optimistic mean for "dropouts" (i.e., patients with missing endpoint data of interest) in the drug arm. We propose an alternative approach in which the missing mean for the drug arm dropouts is explicitly replaced with either the estimated mean of the entire endpoint distribution under placebo (primary analysis) or a sequence of increasingly more conservative means within a tipping point framework (sensitivity analysis); patient-level imputation is not required. A supplemental "dropout = failure" analysis is considered in which a common poor outcome is imputed for all dropouts followed by a between-treatment comparison using quantile regression. All analyses address the same estimand and can adjust for baseline covariates. Three examples and simulation results are used to support our recommendations.
    背景与目标: : 在一些随机 (药物与安慰剂) 临床试验中,感兴趣的估计是临床终点的人群治疗间差异,该临床终点不受 “抢救” 药物的混杂作用 (例如,hbA1c在24周时与基线相比的变化,无论是否或何时终止分配的治疗,在没有抢救药物的情况下都会观察到).在这种情况下,如果某些患者在试验中过早退出试验或开始使用抢救药物,则会出现数据丢失的问题,后者需要丢弃抢救后的数据。我们警告说,常用的混合效应模型重复测量分析与随机假设的嵌入缺失可以提供对上述感兴趣估计的夸大估计。发生这种情况的部分原因是对药物组中 “辍学” (即缺少感兴趣的终点数据的患者) 过于乐观的均值进行了隐含的估算。我们提出了一种替代方法,其中将药物组辍学的缺失平均值明确替换为安慰剂下的整个终点分布的估计平均值 (主要分析) 或在临界点框架内的一系列越来越保守的平均值 (敏感性分析); 不需要患者水平的估算。考虑了补充的 “辍学 = 失败” 分析,其中对所有辍学进行了共同的不良结果估算,然后使用分位数回归进行治疗之间的比较。所有分析都针对相同的估计,并且可以针对基线协变量进行调整。使用了三个示例和仿真结果来支持我们的建议。
  • 【从临床数据中检测有效草药处方的多阶段分析方法。】 复制标题 收藏 收藏
    DOI:10.1007/s11684-017-0525-8 复制DOI
    作者列表:Yang K,Zhang R,He L,Li Y,Liu W,Yu C,Zhang Y,Li X,Liu Y,Xu W,Zhou X,Liu B
    BACKGROUND & AIMS: :Determining effective traditional Chinese medicine (TCM) treatments for specific disease conditions or particular patient groups is a difficult issue that necessitates investigation because of the complicated personalized manifestations in real-world patients and the individualized combination therapies prescribed in clinical settings. In this study, a multistage analysis method that integrates propensity case matching, complex network analysis, and herb set enrichment analysis was proposed to identify effective herb prescriptions for particular diseases (e.g., insomnia). First, propensity case matching was applied to match clinical cases. Then, core network extraction and herb set enrichment were combined to detect core effective herb prescriptions. Effectiveness-based mutual information was used to detect strong herb-symptom relationships. This method was applied on a TCM clinical data set with 955 patients collected from well-designed observational studies. Results revealed that groups of herb prescriptions with higher effectiveness rates (76.9% vs. 42.8% for matched samples; 94.2% vs. 84.9% for all samples) compared with the original prescriptions were found. Particular patient groups with symptom manifestations were also identified to help investigate the indications of the effective herb prescriptions.
    背景与目标: : 确定针对特定疾病或特定患者群体的有效中药 (TCM) 治疗是一个困难的问题,需要进行调查,因为现实世界患者中复杂的个性化表现以及临床环境中规定的个性化组合疗法。在这项研究中,提出了一种结合倾向案例匹配,复杂网络分析和草药集富集分析的多阶段分析方法,以识别针对特定疾病 (例如失眠) 的有效草药处方。首先,将倾向病例匹配应用于临床病例匹配。然后,将核心网络提取和草药集富集相结合,以检测核心有效草药处方。基于有效性的互信息用于检测强烈的草药-症状关系。该方法应用于从精心设计的观察性研究中收集的955名患者的中医临床数据集。结果显示,与原始处方相比,发现了具有更高有效率的草药处方组 (匹配样品为76.9% 对42.8%; 所有样品为94.2% 对84.9%)。还确定了具有症状表现的特定患者组,以帮助调查有效草药处方的适应症。
  • 【LAS: 支持肿瘤数据管理的软件平台。】 复制标题 收藏 收藏
    DOI:10.1007/s10916-012-9891-6 复制DOI
    作者列表:Baralis E,Bertotti A,Fiori A,Grand A
    BACKGROUND & AIMS: :The rapid technological evolution in the biomedical and molecular oncology fields is providing research laboratories with huge amounts of complex and heterogeneous data. Automated systems are needed to manage and analyze this knowledge, allowing the discovery of new information related to tumors and the improvement of medical treatments. This paper presents the Laboratory Assistant Suite (LAS), a software platform with a modular architecture designed to assist researchers throughout diverse laboratory activities. The LAS supports the management and the integration of heterogeneous biomedical data, and provides graphical tools to build complex analyses on integrated data. Furthermore, the LAS interfaces are designed to ease data collection and management even in hostile environments (e.g., in sterile conditions), so as to improve data quality.
    背景与目标: : 生物医学和分子肿瘤学领域的快速技术发展为研究实验室提供了大量复杂和异构的数据。需要自动化系统来管理和分析这些知识,从而可以发现与肿瘤有关的新信息并改善医学治疗。本文介绍了实验室助理套件 (LAS),这是一个具有模块化体系结构的软件平台,旨在帮助研究人员完成各种实验室活动。LAS支持异构生物医学数据的管理和集成,并提供图形工具来对集成数据进行复杂分析。此外,LAS接口被设计成即使在恶劣的环境中 (例如,在无菌条件下) 也易于数据收集和管理,从而提高数据质量。
  • 【印度孕产妇保健支出负担: 国家数据的多层次分析。】 复制标题 收藏 收藏
    DOI:10.1007/s10995-012-1174-9 复制DOI
    作者列表:Leone T,James KS,Padmadas SS
    BACKGROUND & AIMS: :To quantify the economic burden of maternal health care services on Indian households and examine the levels of expenditure incurred in public and private health care institutions at the national, state and community levels. Cross-sectional population data from the 2004 National Sample Survey Organisation were used, which considered 9,643 households for the analysis where at least one woman received maternal health care services during the year preceding the survey. Multilevel linear regression techniques were used to estimate the effect of household, cluster and state characteristics on the proportion of maternal health care expenditures over total household expenditures. Over 80 % of households reported paying for maternal health care services, with those using private care facilities paying almost 4 times more than those using public facilities. Multilevel analyses show evidence of high burden of maternal health care expenditures, which varied significantly across states according to the level of health care utilisation, and with considerable heterogeneity at the household and community levels. Maternal health care services in India are offered free at the point of delivery, yet many families face significant out-of-pocket expenditures. The recent governmental policy interventions to encourage institutional births by providing nominal financial assistance is a welcome step but this might not help to compensate mothers for other indirect expenditures, especially those living in rural areas and poorer communities who are increasingly seeking care in private facilities.
    背景与目标: : 量化孕产妇保健服务对印度家庭的经济负担,并检查国家,州和社区各级公共和私人保健机构的支出水平。使用了2004全国抽样调查组织的横断面人口数据,该数据考虑了9,643家庭进行分析,其中至少有一名妇女在调查前一年接受了孕产妇保健服务。使用多级线性回归技术来估计家庭,集群和州特征对孕产妇保健支出占家庭总支出的比例的影响。超过80% 的家庭报告为孕产妇保健服务付费,使用私人护理设施的家庭付费几乎是使用公共设施的家庭付费的4倍。多层次分析表明,孕产妇保健支出负担很高,根据保健利用水平,各州之间的差异很大,并且在家庭和社区层面具有相当大的异质性。印度的产妇保健服务在分娩时免费提供,但许多家庭面临着大量的自付费用。最近的政府政策干预措施通过提供名义财政援助来鼓励机构分娩是一个可喜的步骤,但这可能无助于补偿母亲的其他间接支出,特别是那些生活在农村地区和贫困社区的母亲,他们越来越多地在私人设施中寻求护理。
  • 【使用PC/AT对微神经图尖峰数据进行自动分类和分析。】 复制标题 收藏 收藏
    DOI:10.1016/0165-0270(90)90155-9 复制DOI
    作者列表:Forster C,Handwerker HO
    BACKGROUND & AIMS: :Using a standard PC-AT with a commercial analog data interface a system was designed which supports microneurographic experiments and which may also be used for other types of extracellular spike recordings. The signal is sampled on-line at 25 kHz and a spike is detected if the signal passes a certain threshold. The spikes are displayed on the screen and stored on disk. A second on-line mode records the responses of the examined unit to electrical stimulations, which are used to identify the type of fibre and to test the subsequent spike classification. The spikes are classified off-line using a template matching algorithm, which has unsupervised learning and discrimination phases. The results are displayed in a time-frequency plot and may be checked with the responses to electrical stimulations. Artifacts from EMG and other electrical fields are reliably sorted out. In recordings, which include more than one unit, their spikes are discriminated with a low error rate.
    背景与目标: : 使用带有商业模拟数据接口的标准pc-at设计了一个系统,该系统支持微神经照相实验,也可用于其他类型的细胞外尖峰记录。信号以25 kHz在线采样,如果信号超过某个阈值,则检测到尖峰。尖峰显示在屏幕上并存储在磁盘上。第二个在线模式记录了被检查单元对电刺激的响应,该响应用于识别光纤的类型并测试随后的尖峰分类。使用模板匹配算法对尖峰进行离线分类,该算法具有无监督的学习和辨别阶段。结果显示在时频图中,并可以通过对电刺激的响应进行检查。可靠地解决了来自EMG和其他电场的伪像。在包含多个单元的录音中,它们的尖峰被区分为低错误率。
  • 【模拟复杂的数据结构,以规划研究,重点是生物标志物比较。】 复制标题 收藏 收藏
    DOI:10.1186/s12874-017-0364-y 复制DOI
    作者列表:Schulz A,Zöller D,Nickels S,Beutel ME,Blettner M,Wild PS,Binder H
    BACKGROUND & AIMS: BACKGROUND:There are a growing number of observational studies that do not only focus on single biomarkers for predicting an outcome event, but address questions in a multivariable setting. For example, when quantifying the added value of new biomarkers in addition to established risk factors, the aim might be to rank several new markers with respect to their prediction performance. This makes it important to consider the marker correlation structure for planning such a study. Because of the complexity, a simulation approach may be required to adequately assess sample size or other aspects, such as the choice of a performance measure. METHODS:In a simulation study based on real data, we investigated how to generate covariates with realistic distributions and what generating model should be used for the outcome, aiming to determine the least amount of information and complexity needed to obtain realistic results. As a basis for the simulation a large epidemiological cohort study, the Gutenberg Health Study was used. The added value of markers was quantified and ranked in subsampling data sets of this population data, and simulation approaches were judged by the quality of the ranking. One of the evaluated approaches, the random forest, requires original data at the individual level. Therefore, also the effect of the size of a pilot study for random forest based simulation was investigated. RESULTS:We found that simple logistic regression models failed to adequately generate realistic data, even with extensions such as interaction terms or non-linear effects. The random forest approach was seen to be more appropriate for simulation of complex data structures. Pilot studies starting at about 250 observations were seen to provide a reasonable level of information for this approach. CONCLUSIONS:We advise to avoid oversimplified regression models for simulation, in particular when focusing on multivariable research questions. More generally, a simulation should be based on real data for adequately reflecting complex observational data structures, such as found in epidemiological cohort studies.
    背景与目标:
  • 【通过流行病学数据post-PCV7的动态建模估算肺炎球菌疫苗效力的地理差异。】 复制标题 收藏 收藏
    DOI:10.1038/s41598-017-02955-y 复制DOI
    作者列表:Gjini E
    BACKGROUND & AIMS: :Although mean efficacy of multivalent pneumococcus vaccines has been intensively studied, variance in vaccine efficacy (VE) has been overlooked. Different net individual protection across settings can be driven by environmental conditions, local serotype and clonal composition, as well as by socio-demographic and genetic host factors. Understanding efficacy variation has implications for population-level effectiveness and other eco-evolutionary feedbacks. Here I show that realized VE can vary across epidemiological settings, by applying a multi-site-one-model approach to data post-vaccination. I analyse serotype prevalence dynamics following PCV7, in asymptomatic carriage in children attending day care in Portugal, Norway, France, Greece, Hungary and Hong-Kong. Model fitting to each dataset provides site-specific estimates for vaccine efficacy against acquisition, and pneumococcal transmission parameters. According to this model, variable serotype replacement across sites can be explained through variable PCV7 efficacy, ranging from 40% in Norway to 10% in Hong-Kong. While the details of how this effect is achieved remain to be determined, here I report three factors negatively associated with the VE readout, including initial prevalence of serotype 19F, daily mean temperature, and the Gini index. The study warrants more attention on local modulators of vaccine performance and calls for predictive frameworks within and across populations.
    背景与目标: : 尽管已经深入研究了多价肺炎球菌疫苗的平均效力,但疫苗效力 (VE) 的差异却被忽略了。环境条件,当地血清型和克隆组成以及社会人口统计学和遗传宿主因素可以驱动不同环境的净个体保护。了解功效变化会对人口水平的有效性和其他生态进化反馈产生影响。在这里,我表明,通过将多站点一模型的方法应用于疫苗接种后的数据,实现的VE可以在流行病学设置中有所不同。我分析了PCV7之后在葡萄牙,挪威,法国,希腊,匈牙利和香港的日托儿童中无症状携带的血清型患病率动态。对每个数据集的模型拟合提供了针对采集的疫苗功效和肺炎球菌传播参数的特定站点估计。根据该模型,可以通过从挪威的40% 到香港的10% 的可变PCV7功效来解释跨位点的可变血清型替代。尽管如何实现这种效果的细节仍有待确定,但在这里我报告了与VE读数负相关的三个因素,包括血清型19F的初始患病率,每日平均温度和基尼指数。该研究需要更多地关注疫苗性能的局部调节剂,并呼吁在人群内部和人群之间建立预测框架。
  • 【降低ST段抬高型心肌梗死放射状入路围手术期死亡率和出血率。来自ORPKI波兰国家注册中心的数据的倾向得分分析。】 复制标题 收藏 收藏
    DOI:10.4244/EIJ-D-17-00078 复制DOI
    作者列表:Siudak Z,Tokarek T,Dziewierz A,Wysocki T,Wiktorowicz A,Legutko J,Żmudka K,Dudek D
    BACKGROUND & AIMS: AIMS:We sought to evaluate bleeding complications and periprocedural outcomes of the radial approach (RA) as compared to the femoral approach (FA) during percutaneous coronary intervention (PCI) in "real-world" patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS:The study group consisted of 22,812 consecutive patients with STEMI treated with PCI and stent implantation between January 2014 and June 2015 in 151 tertiary invasive cardiology centres in Poland (the ORPKI Polish National Registry). Patients treated using the RA and FA were compared using a propensity score analysis to avoid possible selection bias. The analysis was carried out in an "as-treated" manner. The FA was used in 9,334 (40.9%) and the RA in 13,478 (59.1%) patients. After propensity score matching, a higher total amount of contrast (191.8±8.0 vs. 174.8±68.8 ml; p=0.001) and lower radiation doses (1,279.5±1,346.3 vs. 1,182.6±887 mGy; p=0.02) were reported in FA. More access-site-related bleeding complications after both angiography (0.17% vs. 0.02%; p=0.004) and PCI (0.23% vs. 0.09%; p=0.049) were reported in the FA group. Periprocedural death (1.94% vs. 0.93%; p=0.001) was more common after PCI performed with the FA. CONCLUSIONS:The radial approach was associated with a lower incidence of periprocedural death in STEMI patients as well as a significant reduction of bleeding complications at the access site.
    背景与目标:
  • 【通过使用改进的ENDF数据进行辐射捕获,在Cl对n-γ 测井工具的伽马射线光谱影响的数值建模方面取得了进展。】 复制标题 收藏 收藏
    DOI:10.1016/j.apradiso.2006.06.015 复制DOI
    作者列表:Cywicka-Jakiel T
    BACKGROUND & AIMS: :Quality of the numerical modelling (MCNP code) of the spectrometric neutron-gamma benchmark experiment, performed at the Polish Calibration Station BGW in Zielona Gora for quantification of the main rock elements: Si, Ca, Fe and H, is considered. Elemental concentrations obtained from the measurements and simulations, for the rock models with water-filled boreholes, are in good agreement. For chlorine present in the borehole, the quality of the numerical reproducibility of the measured elemental concentrations depends on the cross section library used for the Cl(n,gamma)Cl reaction. The standard evaluated nuclear data library ENDF/B-VI Release 2 supplies imperfect data for photon production from thermal neutron capture in Cl. The improved cross sections for Cl(n,gamma)Cl are included in the ENDF/B-VI Release 8 library. Superiority of this new compilation over the previous one is shown in the paper. The accuracies for the Si, Ca and Fe determination have been improved by about 36%, 19.9% and 21.4%, respectively, when the ENDF/B-VI Release 8 library has been used for Cl.
    背景与目标: : 在Zielona Gora的波兰校准站BGW进行的光谱中子-伽马基准实验的数值建模 (MCNP代码) 的质量,用于定量主要岩石元素: Si,Ca,Fe和H。对于带有注水钻孔的岩石模型,从测量和模拟中获得的元素浓度非常吻合。对于存在于钻孔中的氯,测得的元素浓度的数值重现性的质量取决于用于Cl(n,γ) Cl反应的横截面库。标准评估的核数据库ENDF/b-vi第2版提供了Cl中热中子俘获光子产生的不完善数据。Cl(n,γ) Cl的改进横截面包含在ENDF/b-vi版本8库中。本文显示了此新编译比前一个编译的优越性。当将ENDF/b-vi版本8文库用于Cl时,Si、Ca和Fe测定的准确度分别提高了约36% 、19.9% 和21.4%。
  • 【使用负训练数据对蛋白质-配体相互作用进行评分的参数估计。】 复制标题 收藏 收藏
    DOI:10.1021/jm050040j 复制DOI
    作者列表:Pham TA,Jain AN
    BACKGROUND & AIMS: :Surflex-Dock employs an empirically derived scoring function to rank putative protein-ligand interactions by flexible docking of small molecules to proteins of known structure. The scoring function employed by Surflex was developed purely on the basis of positive data, comprising noncovalent protein-ligand complexes with known binding affinities. Consequently, scoring function terms for improper interactions received little weight in parameter estimation, and an ad hoc scheme for avoiding protein-ligand interpenetration was adopted. We present a generalized method for incorporating synthetically generated negative training data, which allows for rigorous estimation of all scoring function parameters. Geometric docking accuracy remained excellent under the new parametrization. In addition, a test of screening utility covering a diverse set of 29 proteins and corresponding ligand sets showed improved performance. Maximal enrichment of true ligands over nonligands exceeded 20-fold in over 80% of cases, with enrichment of greater than 100-fold in over 50% of cases.
    背景与目标: : Surflex-Dock采用经验推导的评分函数,通过小分子与已知结构的蛋白质的灵活对接,对推定的蛋白质-配体相互作用进行排名。Surflex采用的评分功能是纯粹基于阳性数据开发的,包括具有已知结合亲和力的非共价蛋白质-配体复合物。因此,对于不正确的相互作用的评分函数项在参数估计中几乎没有权重,并且采用了一种避免蛋白质-配体相互渗透的临时方案。我们提出了一种通用方法,用于合并综合生成的负训练数据,该方法可以对所有评分函数参数进行严格估计。在新的参数化下,几何对接精度仍然非常好。此外,涵盖29种蛋白质和相应配体组的筛选效用测试显示出改进的性能。在超过80% 的情况下,非配体上真正配体的最大富集超过20倍,在超过50% 的情况下,富集超过100倍。
  • 【青光眼噪声视野数据的人工神经网络分析。】 复制标题 收藏 收藏
    DOI:10.1016/s0933-3657(97)00388-6 复制DOI
    作者列表:Henson DB,Spenceley SE,Bull DR
    BACKGROUND & AIMS: This paper reports on the application of an artificial neural network to the clinical analysis of ophthalmological data. In particular a 2-dimensional Kohonen self-organising feature map (SOM) is used to analyse visual field data from glaucoma patients. Importantly, the paper addresses the problem of how the SOM can be utilised to accommodate the noise within the data. This is a particularly important problem within longitudinal assessment, where detecting significant change is the crux of the problem in clinical diagnosis. Data from 737 glaucomatous visual field records (Humphrey Visual Field Analyzer, program 24-2) are used to train a SOM with 25 nodes organised on a square grid. The SOM clusters the data organising the output map such that fields with early and advanced loss are at extreme positions, with a continuum of change in place and extent of loss represented by the intervening nodes. For each SOM node 100 variants, generated by a computer simulation modelling the variability that might be expected in a glaucomatous eye, are also classified by the network to establish the extent of noise upon classification. Field change is then measured with respect to classification of a subsequent field, outside the area defined by the original field and its variants. The significant contribution of this paper is that the spatial analysis of the field data, which is provided by the SOM, has been augmented with noise analysis enhancing the visual representation of longitudinal data and enabling quantification of significant class change.

    背景与目标: 本文报告了人工神经网络在眼科数据临床分析中的应用。特别是二维Kohonen自组织特征图 (SOM) 用于分析青光眼患者的视野数据。重要的是,本文解决了如何利用SOM来容纳数据中的噪声的问题。在纵向评估中,这是一个特别重要的问题,在纵向评估中,检测出明显的变化是临床诊断问题的关键。来自737青光眼视野记录 (Humphrey视野分析仪,程序24-2) 的数据用于训练具有25个节点的SOM在方形网格上。SOM对组织输出图的数据进行聚类,以使具有早期和高级损失的字段处于极端位置,并且由中间节点表示连续的变化和损失程度。对于每个SOM节点100变体,由对青光眼眼中可能预期的可变性建模的计算机模拟生成,也由网络分类以建立分类时的噪声程度。然后,针对原始字段及其变体定义的区域之外的后续字段的分类来测量字段变化。本文的重要贡献在于,由SOM提供的现场数据的空间分析已通过噪声分析得到了增强,从而增强了纵向数据的视觉表示并能够量化重大的类别变化。
  • 【胆固醇晶体,平滑肌细胞和动脉粥样硬化发生的新数据。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Kiyak JH
    BACKGROUND & AIMS: The histologic appearance of atherosclerosis has been well described but its pathogenesis is still vigorously debated. The purpose of the present study is to clarify the stimuli for smooth muscle cells (SMC) migration and proliferation as well as the way of cholesterol crystals (CC) generation. We performed postmortem ultrastructural analysis of myocardial samples obtained from 45 patients (33 males, 12 females, age range 18-85) who died from different diseases, mainly from acute myocardial infarction-MI (37 cases). Tissue was taken by transthorax express-necropsy method immediately after patients' death in the clinic. In myocardial infarction cases intact zones of the heart were examined. We have found a few foci of modified SMC proliferation in the periarteriolar space around necrotic cellular debris in elder patients. Lymphocytes, myofibroblasts and some leukocytes infiltrated those areas. The modified SMC phagocyted necrotic material and formed secondary lysosomes, inside which from one to three CC originated. In parallel with the reduction of necrotic mass inside the lysosomes, CC size increased. In the final phase the CC were discharged from the SMC into the interstitium. After exocytosis a tendency for the CC to accumulate was observed. They formed clusters consisting of 20-30 crystals. Most of the CC were of typical needle-like or rhomboid shape. Modified SMC were producing not only CC but also collagen and elastin. This study indicates that atherosclerotic process in the myocardium is connected with the appearance of modified SMC inside which CC are generated.

    背景与目标: 动脉粥样硬化的组织学表现已得到很好的描述,但其发病机理仍在激烈辩论中。本研究的目的是阐明平滑肌细胞 (SMC) 迁移和增殖的刺激以及胆固醇晶体 (CC) 产生的方式。我们对45例死于不同疾病的患者 (男33例,女12例,年龄18-85岁) 的心肌样本进行了死后超微结构分析,这些患者主要死于急性心肌梗死 (MI) (37例)。患者在诊所死亡后,立即通过经胸快速尸检方法采集组织。在心肌梗塞病例中,检查了心脏的完整区域。我们在老年患者坏死细胞碎片周围的小动脉周围发现了一些SMC增殖的病灶。淋巴细胞、肌成纤维细胞和一些白细胞浸润这些区域。修饰的SMC吞噬了坏死物质,并形成了次级溶酶体,在其中产生了一到三个CC。与溶酶体内坏死质量减少同时,CC大小增加。在最后阶段,CC从SMC排放到间质中。胞吐后,观察到CC积累的趋势。他们形成了由20-30个晶体组成的簇。大多数CC为典型的针状或菱形形状。改性SMC不仅产生CC,还产生胶原蛋白和弹性蛋白。这项研究表明,心肌中的动脉粥样硬化过程与内部产生CC的改良SMC的出现有关。
  • 【在病例对照研究中检验单倍型和表型之间的关联: 使用模拟和真实数据检查从队列或临床试验到病例对照样本的算法应用的有效性。】 复制标题 收藏 收藏
    DOI:10.1534/genetics.105.054452 复制DOI
    作者列表:Furihata S,Ito T,Kamatani N
    BACKGROUND & AIMS: :The use of haplotype information in case-control studies is an area of focus for the research on the association between phenotypes and genetic polymorphisms. We examined the validity of the application of the likelihood-based algorithm, which was originally developed to analyze the data from cohort studies or clinical trials, to the data from case-control studies. This algorithm was implemented in a computer program called PENHAPLO. In this program, haplotype frequencies and penetrances are estimated using the expectation-maximization algorithm, and the haplotype-phenotype association is tested using the generalized likelihood ratio. We show that this algorithm was useful not only for cohort studies but also for case-control studies. Simulations under the null hypothesis (no association between haplotypes and phenotypes) have shown that the type I error rates were accurately estimated. The simulations under alternative hypotheses showed that PENHAPLO is a robust method for the analysis of the data from case-control studies even when the haplotypes were not in HWE, although real penetrances cannot be estimated. The power of PENHAPLO was higher than that of other methods using the likelihood-ratio test for the comparison of haplotype frequencies. Results of the analysis of real data indicated that a significant association between haplotypes in the SAA1 gene and AA-amyloidosis phenotype was observed in patients with rheumatoid arthritis, thereby suggesting the validity of the application of PENHAPLO for case-control data.
    背景与目标: : 在病例对照研究中使用单倍型信息是研究表型与遗传多态性之间关联的重点领域。我们检查了基于可能性的算法的应用的有效性,该算法最初是为分析来自队列研究或临床试验的数据而开发的,以及来自病例对照研究的数据。此算法是在称为PENHAPLO的计算机程序中实现的。在该程序中,使用期望最大化算法估计单倍型频率和渗透率,并使用广义似然比测试单倍型-表型关联。我们证明了该算法不仅对队列研究有用,而且对病例对照研究也很有用。在零假设下的模拟 (单倍型和表型之间没有关联) 表明,I型错误率是准确估计的。在替代假设下的模拟表明,即使单倍型不在HWE中,PENHAPLO也是分析病例对照研究数据的可靠方法,尽管无法估计实际的渗透率。使用似然比检验比较单倍型频率,PENHAPLO的能力高于其他方法。对真实数据的分析结果表明,在类风湿关节炎患者中观察到SAA1基因的单倍型与AA-淀粉样变表型之间存在显着关联,从而表明PENHAPLO在病例对照数据中的应用是有效的。
  • 【关于差异表达基因的鉴定: 改进Affymetrix微阵列基因表达数据的广义F统计量。】 复制标题 收藏 收藏
    DOI:10.1016/j.compbiolchem.2006.06.002 复制DOI
    作者列表:Lai Y
    BACKGROUND & AIMS: :It has been shown that the generalized F-statistics can give satisfactory performances in identifying differentially expressed genes with microarray data. However, for some complex diseases, it is still possible to identify a high proportion of false positives because of the modest differential expressions of disease related genes and the systematic noises of microarrays. The main purpose of this study is to develop statistical methods for Affymetrix microarray gene expression data so that the impact on false positives from non-expressed genes can be reduced. I proposed two novel generalized F-statistics for identifying differentially expressed genes and a novel approach for estimating adjusting factors. The proposed statistical methods systematically combine filtering of non-expressed genes and identification of differentially expressed genes. For comparison, the discussed statistical methods were applied to an experimental data set for a type 2 diabetes study. In both two- and three-sample analyses, the proposed statistics showed improvement on the control of false positives.
    背景与目标: : 已经表明,广义F统计量可以在用微阵列数据鉴定差异表达基因方面提供令人满意的性能。然而,对于一些复杂的疾病,由于疾病相关基因的适度差异表达和微阵列的系统噪声,仍然有可能识别出高比例的假阳性。这项研究的主要目的是开发Affymetrix微阵列基因表达数据的统计方法,以便可以减少对非表达基因假阳性的影响。我提出了两种新颖的通用F统计量来识别差异表达的基因,以及一种估计调整因子的新方法。所提出的统计方法系统地结合了非表达基因的过滤和差异表达基因的鉴定。为了进行比较,将讨论的统计方法应用于2型糖尿病研究的实验数据集。在两样本和三样本分析中,建议的统计数据均显示出对假阳性的控制有所改善。

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