• 【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:
  • 【在大量,多样化的系统性红斑狼疮患者和家庭成员中,传统和基于珠子的检测之间的自身抗体特异性比较。】 复制标题 收藏 收藏
    DOI:10.1002/art.34651 复制DOI
    作者列表:Bruner BF,Guthridge JM,Lu R,Vidal G,Kelly JA,Robertson JM,Kamen DL,Gilkeson GS,Neas BR,Reichlin M,Scofield RH,Harley JB,James JA
    BACKGROUND & AIMS: OBJECTIVE:Replacement of standard immunofluorescence methods with bead-based assays for antinuclear antibody (ANA) testing is a new clinical option. The aim of this study was to evaluate a large, multiethnic cohort of patients with systemic lupus erythematosus (SLE), blood relatives, and unaffected control individuals for familial aggregation and subset clustering of autoantibodies by high-throughput serum screening technology and traditional methods. METHODS:Serum samples (1,540 SLE patients, 1,154 unaffected relatives, and 906 healthy, population-based controls) were analyzed for SLE autoantibodies using a bead-based assay, indirect immunofluorescence (IIF), and immunodiffusion. Autoantibody prevalence, sensitivity for disease detection, clustering of autoantibodies, and associations between newer methods and standard immunodiffusion results were evaluated. RESULTS:The frequencies of ANAs in the sera from African American, Hispanic, and European American patients with SLE were 89%, 73%, and 67%, respectively, by BioPlex 2200 bead-based assay and 94%, 84%, and 86%, respectively, by IIF. When comparing the serum prevalence of 60-kd Ro, La, Sm, nuclear RNP A, and ribosomal P autoantibodies across assays, the sensitivity of detection ranged from 0.92 to 0.83 and the specificity ranged from 0.90 to 0.79. Autoantibody cluster analysis showed associations of autoantibody specificities in 3 subsets: 1) 60 kd Ro, 52-kd Ro, and La, 2) spliceosomal proteins, and 3) double-stranded DNA (dsDNA), chromatin, and ribosomal P. Familial aggregation of Sm/RNP, ribosomal P, and 60-kd Ro in SLE patient sibling pairs was observed (P ≤ 0.004). Simplex-pedigree SLE patients had a greater prevalence of dsDNA (P = 0.0003) and chromatin (P = 0.005) autoantibodies compared to patients with a multiplex SLE pedigree. CONCLUSION:The frequencies of ANAs detected by a bead-based assay are lower than those detected by IIF in European American patients with SLE. These assays have strong positive predictive values across ethnic groups, provide useful information for clinical care, and provide unique insights into familial aggregation and autoantibody clustering.
    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。
  • 【极低体重婴儿的PBSC收集: 单中心体验。】 复制标题 收藏 收藏
    DOI:10.1080/14653240701320270 复制DOI
    作者列表:Sevilla J,Plaza SF,González-Vicent M,Lassaletta A,Ramírez M,Madero L,Díaz MA
    BACKGROUND & AIMS: BACKGROUND:Peripheral blood progenitor cell (PBPC) collection has become the main source of hematopoietic cells for high-dose chemotherapy with stem cell rescue and, in some protocols, for allogeneic hematopoietic transplantation. This procedure is complicated in the smallest children because of difficulties related to their weight, and there is little published experience. We have conducted a prospective study to analyze the incidence of adverse events during PBPC collection in the smallest children (< or = 10 kg). METHODS:From January 2000 to November 2005, 257 leukapheresis were performed in our unit, and 13 of them (5%) in 12 children weighing up to 10 kg (median 9 kg, range 5.8-10.9 kg). RESULTS:Most cases had hypovolemic signs during the procedure (usually tachycardia); six cases had hypotension, five of them with pallor and diaphoresis, and, of those, two also had nausea. In all these cases infusion of saline or plasma volume expanders resolved the clinical findings. In two cases the nausea related to hypocalcemia was resolved after calcium gluconate infusion. Changes in platelet counts were also remarkable, with a median platelet loss of 52%. DISCUSSION:Leukapheresis with continuous-flow cell separators has frequent complications related to volume shift in the smallest children. These adverse events are mild and easily resolved with standard measures for hypovolemia, as plasma expander or normal saline infusions. However, we recommend that the procedure should only be performed by teams with extensive experience in the field.
    背景与目标:
  • 【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。
  • 【基于中性损失的磷酸肽识别: 一系列警告。】 复制标题 收藏 收藏
    DOI:10.1021/pr060573w 复制DOI
    作者列表:Lehmann WD,Krüger R,Salek M,Hung CW,Wolschin F,Weckwerth W
    BACKGROUND & AIMS: :The standard strategy for analysis by tandem mass spectrometry of protein phosphorylation at serine or threonine utilizes the neutral loss of H3PO4 (= 97.977/z) from proteolytic peptide molecular ions as marker fragmentation. Manual control of automatically performed neutral loss-based phosphopeptide identifications is strongly recommended, since these data may contain false-positive results. These are connected to the experimental neutral loss m/z error, to competing peptide fragmentation pathways, to limitations in data interpretation software, and to the general growth of protein sequence databases. The fragmentation-related limitations of the neutral loss approach cover (i) the occurrence of abundant 'close-to-98/z' neutral loss fragmentations, (ii) the erroneous assignment of a neutral loss other than loss of H3PO4 due to charge state mix-up, and (iii) the accidental occurrence of any fragment ion in the m/z windows of interest in combination with a charge-state mix-up. The 'close-to-98/z' losses comprise loss of proline (97.053/z), valine (99.068/z), threonine (101.048/z), or cysteine (103.009/z) preferably from peptides with N-terminal sequences PP, VP, TP, or CP, and loss of 105.025/z from alkylated methionine. Confusion with other neutral losses may occur, when their m/z window coincides with a 98/z window as result of a charge state mix-up. Neutral loss of sulfenic acid from oxidized methionine originating from a doubly charged precursor (63.998/2 = 31.999) may thus mimic the loss of phosphoric acid from a triply charged phosphopeptide (97.977/3 = 32.659). As a consequence of the large complexity of proteomes, peptide sequence ions may occur in one of the mass windows of H3PO4 loss around 97.977/z. Practical examples for false-positive annotations of phosphopeptides are given for the first two groups of error. The majority of these can be readily recognized using the guidelines presented in this study.
    背景与目标: : 通过串联质谱分析丝氨酸或苏氨酸蛋白磷酸化的标准策略利用蛋白水解肽分子离子中H3PO4 (= 97.977/z) 的中性损失作为标记片段。强烈建议手动控制自动执行的基于中性损失的磷酸肽鉴定,因为这些数据可能包含假阳性结果。这些与实验中性损失m/z误差,竞争性肽片段化途径,数据解释软件的局限性以及蛋白质序列数据库的总体增长有关。中性损失方法与碎片相关的限制涵盖 (i) 大量 “接近98/z” 中性损失碎片的发生,(ii) 由于电荷状态混淆而导致的除了H3PO4损失之外的中性损失的错误分配,(iii) 在感兴趣的m/z窗口中意外发生任何碎片离子,并结合电荷状态混合。“接近-98/z” 损失包括脯氨酸 (97.053/z) 、缬氨酸 (99.068/z) 、苏氨酸 (101.048/z) 或半胱氨酸 (103.009/z) 的损失,优选地来自具有N端序列PP、VP、TP或CP的肽,以及烷基化甲硫氨酸的105.025/z的损失。当电荷状态混合导致其m/z窗口与98/z窗口重合时,可能会发生与其他中性损耗的混淆。源自双重电荷前体 (63.998/2 = 31.999) 的氧化蛋氨酸的亚砜酸的中性损失因此可以模拟来自三重电荷磷酸肽 (97.977/3 = 32.659) 的磷酸的损失。由于蛋白质组的大量复杂性,肽序列离子可能出现在H3PO4丢失的质量窗口之一中,约97.977/z。针对前两组错误,给出了磷酸肽假阳性注释的实际示例。使用本研究中提出的指南可以很容易地识别出其中的大多数。
  • 【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。
  • 【执法机构防弹衣政策简介-LEMAS 2013数据的潜在类分析。】 复制标题 收藏 收藏
    DOI:10.1080/15459624.2017.1339163 复制DOI
    作者列表:Liu W,Taylor B
    BACKGROUND & AIMS: :The life-saving benefits of body armor have been well-documented, and law enforcement agency (LEA) body armor wear requirements have been cited by police officers as one of the most important reasons for them to wear body armor. However, research on LEAs' policies and practices regarding body armor is scarce. This study examined whether there are different agency-level profiles of various body armor-related policies, and related these body armor policy profiles to agency characteristics, size, location, etc. U.S. LEAs fell into four distinct profiles based on their body armor policies. Close to half of the LEAs had comprehensive coverage of body armor policies in all aspects. However, nearly one in five LEAs had very weak body armor policies in all aspects. The rest of the LEAs split into two groups, each with different strengths and weaknesses on selection, training, fitting, wearing, and inspection policies. Sheriff's offices and smaller LEAs were found to have weaker policies. In contrast, LEAs with a community policing emphasis and those with body armor grants were found to have stronger body armor polices, especially when it comes to mandatory wearing polices. Findings from the study provide a portrait of the current state of LEA body armor policies, and provide guidance for improving LEAs' body armor policies and practices.
    背景与目标: : 防弹衣的救生好处已有据可查,执法机构 (LEA) 的防弹衣穿着要求已被警察引用为他们穿着防弹衣的最重要原因之一。但是,有关leas关于防弹衣的政策和实践的研究很少。这项研究检查了各种与防弹衣相关的政策是否存在不同的机构级别的配置文件,并将这些防弹衣政策配置文件与机构特征,规模,位置等相关。美国LEAs根据其防弹衣政策分为四个不同的配置文件。近一半的lea在各个方面都全面覆盖了防弹衣政策。但是,近五分之一的lea在各个方面的防弹衣政策都非常薄弱。Lea的其余部分分为两组,每组在选择,培训,装配,穿着和检查政策方面都有不同的优缺点。发现警长办公室和较小的lea的政策较弱。相比之下,以社区警务为重点的lea和拥有防弹衣补助金的lea被发现具有更强的防弹衣政策,尤其是在强制性穿戴政策方面。研究结果提供了LEA防弹衣政策的现状,并为改善leas的防弹衣政策和实践提供了指导。
  • 【谈论人类乳头瘤病毒和癌症: 通过使用定性,定量和次要数据的专业利益相关者共同生产制定咨询指南。】 复制标题 收藏 收藏
    DOI:10.1136/bmjopen-2016-015413 复制DOI
    作者列表:Hendry M,Pasterfield D,Gollins S,Adams R,Evans M,Fiander A,Robling M,Campbell C,Bekkers MJ,Hiscock J,Nafees S,Rose J,Stanley M,Williams O,Makin M,Wilkinson C
    BACKGROUND & AIMS: BACKGROUND:High-risk human papillomaviruses (HPVs) cause all cervical cancer and the majority of vulvar, vaginal, anal, penile and oropharyngeal cancers. Although HPV is the most common sexually transmitted infection, public awareness of this is poor. In addition, many clinicians lack adequate knowledge or confidence to discuss sexual transmission and related sensitive issues. Complex science needs to be communicated in a clear, digestible, honest and salient way. Therefore, the aim of this study was to coproduce with patients who have cancer appropriate resources to guide these highly sensitive and difficult consultations. METHODS:A matrix of evidence developed from a variety of sources, including a systematic review and telephone interviews with clinicians, supported the production of a draft list of approximately 100 potential educational messages. These were refined in face-to-face patient interviews using card-sorting techniques, and tested in cognitive debrief interviews to produce a ‘fast and frugal’ knowledge tool. RESULTS:We developed three versions of a consultation guide, each comprising a clinician guidance sheet and patient information leaflet for gynaecological (cervical, vaginal, vulvar), anal or oropharyngeal cancers. That cancer could be caused by a sexually transmitted virus acquired many years previously was surprising to many and shocking to a few patients. However, they found the information clear, helpful and reassuring. Clinicians acknowledged a lack of confidence in explaining HPV, welcomed the clinician guidance sheets and considered printed information for patients particularly useful. CONCLUSION:Because of the ‘shock factor’, clinicians will need to approach the discussion of HPV with sensitivity and take individual needs and preferences into account, but we provide a novel, rigorously developed and tested resource which should have broad applicability in the UK National Health Service and other health systems.
    背景与目标:

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