BACKGROUND & AIMS: :The objective of this study was to evaluate the response of the rat epidermal keratinocyte organotypic culture (ROC) to permeation enhancers, and to compare these responses to those in human cadaver skin. Different concentrations of two mixtures for enhancing permeation were investigated, sodium dodecyl sulfate:phenyl piperazine and methyl pyrrolidone:dodecyl pyridinium chloride, using skin impedance spectroscopy and two experimental compounds, the lipophilic corticosterone and the hydrophilic sucrose. The chemical irritation effects of the formulations were evaluated based on leakage of lactate dehydrogenase enzyme (LDH) and cellular morphological perturbation. This study provides evidence for direct correlations of permeation/permeation, impedance/impedance and permation/impedance between the culture model and human skin. The only exception was the enhancer induced permeation of sucrose which was 1-40-fold higher in ROC compared to human skin, reflecting the more disordered lipid organization in stratum corneum and consequently the greater number of polar pathways. LDH leakage and cellular morphology indicated that it was possible to differentiate between safe permeation enhancers from irritating agents. This is not only the first study to have compared the enhancer effects on a cultured skin model with human skin, but also it has demonstrated enhancer induced irritation using an artificial skin model.

背景与目标： ：这项研究的目的是评估大鼠表皮角质形成细胞器官型培养（ROC）对渗透促进剂的反应，并将这些反应与人体尸体皮肤的反应进行比较。使用皮肤阻抗光谱法和两种实验化合物脂溶性皮质酮和亲水性蔗糖，研究了十二烷基硫酸钠：苯基哌嗪钠和甲基吡咯烷酮：十二烷基吡啶鎓氯化物的两种不同浓度的混合物，以提高渗透性。基于乳酸脱氢酶（LDH）的泄漏和细胞形态扰动来评估制剂的化学刺激作用。这项研究提供了文化模型与人体皮肤之间渗透/渗透，阻抗/阻抗和渗透/阻抗直接相关的证据。唯一的例外是增强剂诱导的蔗糖渗透率在ROC中是人皮肤的1-40倍，这反映了角质层中脂质组织的紊乱程度更大，因此极性途径的数量也更多。 LDH泄漏和细胞形态表明，可以区分安全性增强剂和刺激性剂。这不仅是将人​​皮肤对培养的皮肤模型的增强效果进行比较的第一项研究，而且还证明了使用人工皮肤模型对增强剂引起的刺激作用。

BACKGROUND & AIMS: :Cullin-dependent ubiquitin ligases regulate a variety of cellular and developmental processes by recruiting specific proteins for ubiquitin-mediated degradation. Cullin proteins form a scaffold for two functional modules: a catalytic module comprised of a small RING domain protein Roc1/Rbx1 and a ubiquitin-conjugating enzyme (E2), and a substrate recruitment module containing one or more proteins that bind to and bring the substrate in proximity to the catalytic module. Here, we present evidence that the three Drosophila Roc proteins are not functionally equivalent. Mutation of Roc1a causes lethality that cannot be rescued by expression of Roc1b or Roc2 by using the Roc1a promoter. Roc1a mutant cells hyperaccumulate Cubitus interruptus, a transcription factor that mediates Hedgehog signaling. This phenotype is not rescued by expression of Roc2 and only partially by expression of Roc1b. Targeted disruption of Roc1b causes male sterility that is partially rescued by expression of Roc1a by using the Roc1b promoter, but not by similar expression of Roc2. These data indicate that Roc proteins play nonredundant roles during development. Coimmunoprecipitation followed by Western or mass spectrometric analysis indicate that the three Roc proteins preferentially bind certain Cullins, providing a possible explanation for the distinct biological activities of each Drosophila Roc/Rbx.

背景与目标： ：Cullin依赖性泛素连接酶通过募集特定蛋白进行泛素介导的降解来调节多种细胞和发育过程。 Cullin蛋白形成两个功能模块的支架：一个由小的RING域蛋白Roc1 / Rbx1和泛素结合酶（E2）组成的催化模块，以及一个底物募集模块，其中包含一个或多个与底物结合并带来底物的蛋白质。在催化模块附近。在这里，我们提供证据表明三种果蝇Roc蛋白在功能上不相同。 Roc1a的突变会导致致命性，而使用Roc1a启动子则无法通过表达Roc1b或Roc2挽救其致死性。 Roc1a突变细胞过度积累Cubitus interruptus，一种介导Hedgehog信号传导的转录因子。 Roc2的表达不能挽救这种表型，Roc1b的表达只能挽救一部分。 Roc1b的靶向破坏会导致雄性不育，通过使用Roc1b启动子表达Roc1a可部分挽救雄性不育，而不是通过类似的Roc2表达来恢复。这些数据表明，Roc蛋白在发育过程中起着非冗余的作用。免疫共沉淀后再进行Western或质谱分析表明，这三种Roc蛋白优先结合某些Cullins，为每种果蝇Roc / Rbx的独特生物活性提供了可能的解释。

BACKGROUND & AIMS: :Current ongoing genome-wide association (GWA) studies represent a powerful approach to uncover common unknown genetic variants causing common complex diseases. The discovery of these genetic variants offers an important opportunity for early disease prediction, prevention, and individualized treatment. We describe here a method of combining multiple genetic variants for early disease prediction, based on the optimality theory of the likelihood ratio (LR). Such theory simply shows that the receiver operating characteristic (ROC) curve based on the LR has maximum performance at each cutoff point and that the area under the ROC curve so obtained is highest among that of all approaches. Through simulations and a real data application, we compared it with the commonly used logistic regression and classification tree approaches. The three approaches show similar performance if we know the underlying disease model. However, for most common diseases we have little prior knowledge of the disease model and in this situation the new method has an advantage over logistic regression and classification tree approaches. We applied the new method to the type 1 diabetes GWA data from the Wellcome Trust Case Control Consortium. Based on five single nucleotide polymorphisms, the test reaches medium level classification accuracy. With more genetic findings to be discovered in the future, we believe a predictive genetic test for type 1 diabetes can be successfully constructed and eventually implemented for clinical use.

背景与目标： ：目前正在进行的全基因组关联（GWA）研究代表了一种强大的方法，可揭示导致常见复杂疾病的常见未知遗传变异。这些遗传变异的发现为疾病的早期预测，预防和个体化治疗提供了重要的机会。我们在这里描述一种基于似然比（LR）的最优性理论，将多种遗传变异结合起来进行早期疾病预测的方法。这种理论简单地表明，基于LR的接收机工作特性（ROC）曲线在每个截止点都具有最佳性能，并且在所有方法中，如此获得的ROC曲线下的面积最高。通过仿真和实际数据应用，我们将其与常用的逻辑回归和分类树方法进行了比较。如果我们知道潜在的疾病模型，则这三种方法显示出相似的性能。但是，对于大多数常见疾病，我们几乎没有疾病模型的先验知识，在这种情况下，新方法比逻辑回归和分类树方法更具优势。我们将新方法应用于来自Wellcome Trust病例对照协会的1型糖尿病GWA数据。基于五个单核苷酸多态性，该测试达到中等水平的分类准确性。随着将来发现更多的遗传发现，我们相信可以成功构建1型糖尿病的预测性遗传测试，并最终用于临床。

BACKGROUND & AIMS: :In Clinical Epidemiology, receiver operating characteristic (ROC) analysis is a standard approach for the evaluation of the performance of diagnostic tests for binary classification based on a tumour marker distribution. The area under a ROC curve is a popular indicator of test accuracy, but its use has been questioned when the curve is asymmetric. This situation often happens when the marker concentrations overlap in the two groups under study in the range of low specificity, corresponding to a subset of values useless for classification purposes (non-informative values). The partial area under the curve at a high specificity threshold has been proposed as an alternative, but a method to identify an optimal cut-off that separates informative from non-informative values is not yet available. In this study, a new statistical approach is proposed to perform this task. Furthermore, a statistical test associated with the area under a ROC curve corresponding to informative values only (restricted ROC curve) is provided and its properties are explored by extensive simulations. Finally, the proposed method is applied to a real data set containing peripheral blood levels of six tumour markers proposed for the diagnosis of neuroblastoma. A new approach to combine couples of markers for classification purposes is also illustrated.

背景与目标： ：在临床流行病学中，接受者操作特征（ROC）分析是用于评估基于肿瘤标志物分布的二元分类诊断测试性能的标准方法。 ROC曲线下的面积是测试准确性的常用指标，但是当曲线不对称时，其使用受到质疑。当标记物浓度在低特异性范围内的两组研究中重叠时，通常会发生这种情况，这对应于分类目的无用的值（非信息性值）的子集。已经提出了在高特异性阈值下的曲线下的局部区域作为替代方法，但是尚无法找到一种将信息和非信息值区分开的最佳临界值的方法。在这项研究中，提出了一种新的统计方法来执行此任务。此外，提供了与仅对应于信息性值的ROC曲线下区域（受限的ROC曲线）相关的统计检验，并通过广泛的模拟探索了其性能。最后，将所提出的方法应用于真实数据集，该数据集包含提议用于诊断神经母细胞瘤的六个肿瘤标志物的外周血水平。还说明了一种用于分类目的组合标记对的新方法。

BACKGROUND & AIMS: :The morphological and biochemical changes that occur during chemical hypoxic injury in a neural cell line were studied in the presence and absence of calcium. Oligodendroglial-glioma hybrid cells (ROC-1) were subjected to inhibitors of glycolytic and oxidative ATP synthesis (chemical hypoxia). Complete respiratory inhibition depleted [ATP] to less than 5% of control by 4 min. Blebs appeared on the cell surfaces and cells began to swell within a few minutes of ATP depletion. A 200% increase in cell volume and bleb coalescence preceded irreversible cell injury (lactate dehydrogenase release) which began at approximately 20 min with 50% cell death by 40 min. In energized cells an equivalent degree of osmotic swelling induced by ouabain inhibition of the Na+, K(+)-ATPase pump did not produce blebbing or cell death. Partial inhibition of respiration decreased [ATP] to approximately 10% of control by 40 min. Blebbing and swelling began at 40 min and bleb coalescence preceded plasma membrane disruption which began at approximately 55 min. ATP depletion, blebbing, swelling, and death followed similar time courses in the presence or absence of extracellular calcium ([Ca2+]e). Intracellular calcium ([Ca2+]i) was measured using fura-2. In calcium-containing medium metabolic inhibition caused a transient increase in resting [Ca2+]i (100 +/- 17 nM) followed by a low steady-state level preceding plasma membrane disruption. Following deenergization in calcium-free medium, [Ca2+]i remained below 60 nM throughout injury and death. These data suggest that decreased ATP initiates a sequence of events including bleb formation and cell swelling that lead to irreversible cell injury in the absence of large increases in [Ca2+]i.

背景与目标： ：研究了在有钙和无钙的情况下，神经细胞系在化学性低氧损伤过程中发生的形态和生化变化。少突胶质细胞-神经胶质瘤杂交细胞（ROC-1）受到糖酵解和氧化ATP合成的抑制剂（化学性缺氧）。到4分钟时，完全的呼吸抑制作用使[ATP]减少至控制量的5％以下。小球出现在细胞表面，并且在ATP耗尽的几分钟内细胞开始肿胀。细胞体积增加200％和气泡合并之前发生不可逆的细胞损伤（乳酸脱氢酶释放），这种损伤始于约20分钟，到40分钟时细胞死亡50％。在通电的细胞中，哇巴因对Na，K（）-ATPase泵的抑制作用引起的同等程度的渗透性溶胀不会产生起泡或细胞死亡。到40分钟，对呼吸的部分抑制使[ATP]降至对照的约10％。起泡和溶胀在40分钟开始，起泡聚结在质膜破裂之前发生，其在约55分钟开始。在存在或不存在细胞外钙（[Ca2] e）的情况下，ATP的消耗，起泡，膨胀和死亡也遵循相似的时间过程。使用呋喃2测定细胞内钙（[Ca2] i）。在含钙的培养基中，代谢抑制导致静止的[Ca2] i（100 /-17 nM）短暂增加，随后在质膜破裂之前处于低稳态水平。在无钙培养基中断电后，[Ca2] i在整个伤害和死亡中均保持在60 nM以下。这些数据表明，降低的ATP会引发一系列事件，包括气泡形成和细胞肿胀，在[Ca2] i没有大幅增加的情况下会导致不可逆的细胞损伤。

BACKGROUND & AIMS: :Ras of complex proteins (Roc) belongs to the superfamily of Ras-related small G-proteins that always occurs in tandem with the C-terminal of Roc (COR) domain. This Roc-COR tandem is found in the bacterial and eukaryotic world. Its most prominent member is the leucine-rich repeat kinase LRRK2, which is mutated and activated in Parkinson patients. Here, we investigated biochemically and structurally the Roco protein from Chlorobium tepidum. We show that Roc is highly homologous to Ras, whereas the COR domain is a dimerisation device. The juxtaposition of the G-domains and mutational analysis suggest that the Roc GTPase reaction is stimulated and/or regulated by dimerisation in a nucleotide-dependent manner. The region most conserved between bacteria and man is the interface between Roc and COR, where single-point Parkinson mutations of the Roc and COR domains are in close proximity. The analogous mutations in C. tepidum Roc-COR decrease the GTPase reaction rate, most likely due to a modification of the interaction between the Roc and COR domains.

背景与目标： ：复杂蛋白的Ras（Roc）属于与Ras相关的小G蛋白的超家族，该家族总是与Roc结构域的C端（COR）串联。这种Roc-COR串联结构在细菌和真核生物世界中发现。它最突出的成员是富含亮氨酸的重复激酶LRRK2，在帕金森病患者中被突变并激活。在这里，我们从生化和结构上研究了来自绿皮棉的洛可可蛋白。我们显示Roc与Ras高度同源，而COR域是二聚化设备。 G结构域的并置和突变分析表明，Roc GTPase反应是通过二聚作用以核苷酸依赖性方式刺激和/或调节的。细菌和人之间最保守的区域是Roc和COR之间的界面，Roc和COR域的单点帕金森突变非常接近。破伤风梭菌Roc-COR中的类似突变降低了GTPase反应速率，这很可能是由于Roc和COR域之间相互作用的修饰。

BACKGROUND & AIMS: :Developing prognostic markers of mortality for patients with chronic disease is important for identifying subjects at high risk of death and optimizing medical management. The usual approach in this regard is the use of time-dependent ROC curves, which are well adapted for censored data. Nevertheless, an important part of the mortality may not be due to the chronic disease, and it is often impossible to individually determine whether or not the deaths are related to the disease itself. In survival regression, one solution is to distinguish between the expected mortality of one general population (from life tables) and the excess mortality related to the disease, by using an additive relative survival model. In this paper, we propose a new estimator of time-dependent ROC curves, which includes this concept of net survival, in order to evaluate the capacity of a marker to predict disease-specific mortality. We performed simulations in order to validate this estimator. We also illustrate this method using two different applications: (i) predicting mortality related to primary biliary cirrhosis of the liver and (ii) predicting mortality related to kidney transplantation in end-stage renal disease patients. For each application, we evaluated a scoring system already established. The results demonstrate the utility of the proposed estimator of net time-dependent ROC curves.

背景与目标： ：为慢性病患者开发死亡率的预后标志物对于识别高死亡风险的受试者和优化医疗管理非常重要。在这方面，通常的方法是使用随时间变化的ROC曲线，该曲线非常适合于被检查的数据。然而，死亡率的重要部分可能不是由于慢性疾病引起的，通常无法单独确定死亡是否与疾病本身有关。在生存回归中，一种解决方案是通过使用累加相对生存模型来区分一个普通人群的预期死亡率（从生命表中）和与该疾病有关的超额死亡率。在本文中，我们提出了一种新的估计时间依赖性ROC曲线的方法，其中包括这种净存活率的概念，以便评估标记物预测疾病特异性死亡率的能力。我们进行了仿真，以验证该估计量。我们还使用两种不同的应用说明了该方法：（i）预测与原发性肝硬化肝有关的死亡率，以及（ii）预测与终末期肾脏疾病患者的肾移植有关的死亡率。对于每个应用程序，我们评估了已经建立的评分系统。结果证明了所提出的净时间依赖的ROC曲线估计器的实用性。

BACKGROUND & AIMS: PURPOSE:To compare the diagnostic performance of multirow-detector computed tomography (MDCT) and magnetic resonance imaging (MRI) in the differentiation of intraductal papillary mucinous neoplasms (IPMNs) from other pancreatic cystic masses. MATERIALS AND METHODS:A total of 53 patients with pathologically proven pancreatic cystic lesions who had undergone MDCT and MRI were included in this study. Two radiologists analyzed the morphologic features of the lesions and graded the lesion conspicuity on each examination. The readers assigned their confidence level regarding the differentiation of IPMN from other lesions and predicting ductal communication of the lesion. The radiologists' diagnostic confidence was compared using receiver operating characteristic (ROC) analysis. RESULTS:The Az values for each observer for predicting ductal communication of the lesion and differentiating IPMN from other lesions were as follows: For MRI they were respectively 0.949 and 0.995 for reader 1, and 0.916 and 0.932 for reader 2. For MDCT they were respectively 0.790 and 0.875 for reader 1, and 0.774 and 0.850 for reader 2. In addition, for differentiating IPMNs from other lesions, MRI was significantly more accurate than MDCT (P < 0.05) for one observer, but for the other observer there was no significant difference between the two examinations (P = 0.059). For predicting ductal communication of the cystic lesions for both observers, MRI was significantly more accurate than MDCT (P < 0.05). The weighted kappa values indicate good agreement (kappa = 0.61) between observers for MDCT, and excellent agreement (kappa = 0.82) for MRI. CONCLUSION:Pancreatic MRI shows better diagnostic performance than MDCT for differentiating IPMNs from other cystic lesions of the pancreas.

背景与目标： 目的：比较多排计算机断层扫描（MDCT）和磁共振成像（MRI）在将导管内乳头状黏液性肿瘤（IPMN）与其他胰腺囊性肿块相鉴别的诊断性能。
材料与方法：本研究共纳入53例经MDCT和MRI病理证实的胰腺囊性病变的患者。两名放射科医生分析了病变的形态特征，并在每次检查时对病变的明显程度进行了分级。读者为他们分配了关于IPMN与其他病变的区别以及预测病变的导管通透性的置信度。使用接收器工作特性（ROC）分析比较了放射科医生的诊断置信度。
结果：每个观察者用于预测病变的导管通气并将IPMN与其他病变区分开的Az值如下：对于MRI，阅读器1分别为0.949和0.995，阅读器2分别为0.916和0.932。读取器1的读数分别为0.790和0.875，读取器2的读数为0.774和0.850。此外，对于将IPMN与其他病变区分开来，一位观察者的MRI准确性明显高于MDCT（P <0.05），而另一位观察者则无统计学意义。两次检查之间的差异（P = 0.059）。为了预测两位观察者的囊性病变的导管连通性，MRI比MDCT准确得多（P <0.05）。加权kappa值表示MDCT观察者之间的一致性好（kappa = 0.61），而MRI则具有很好的一致性（kappa = 0.82）。
结论：与其他CT胰腺囊性病变相比，胰腺MRI显示出比MDCT更好的诊断性能。

BACKGROUND & AIMS: UNLABELLED:Energy-weighted acquisition is a technique for reducing Compton scatter effects in nuclear medicine images. The effect of energy-weighted acquisition on SPECT99mTc images was evaluated by comparing the energy-weighted acquisition images with those obtained using a 20% photopeak energy window. METHODS:SPECT images were compared using receiver operator characteristic (ROC) experiments testing the observer's ability to perform a pseudoclinical task. The tasks were detecting cold lesions within a uniform background and cold lesions within images created with a tomographic brain phantom. RESULTS:ROC analysis for each phantom produced different results. No significant difference was found between the two acquisition techniques in detecting cold lesions on uniform backgrounds. Energy-weighted acquisition improved cold lesion detection significantly within the brain phantom in comparison with 20% photopeak acquisition. CONCLUSION:Lesion detection in 99mTcSPECT images can be improved using energy-weighted acquisition. This improvement, however, is dependent on the nature of the object being imaged. Images with structure show improved detection, whereas uniform images do not.

背景与目标： 标注不明确：能量加权采集是一种用于减少核医学图像中康普顿散射效应的技术。通过将能量加权采集图像与使用20％光电峰能量窗口获得的能量加权采集图像进行比较，评估了能量加权采集对SPECT99mTc图像的影响。
方法：使用接收者操作员特征（ROC）实验比较SPECT图像，以测试观察者执行伪临床任务的能力。他们的任务是在均匀背景下检测冷损伤，并在通过层析X线体模创建的图像中检测冷损伤。
结果：每个体模的ROC分析产生不同的结果。在相同背景下检测冷损伤时，两种采集技术之间没有发现显着差异。与20％的光峰采集相比，能量加权采集显着改善了脑部幻影内的冷病变检测。
结论：利用能量加权采集可以改善99mTcSPECT图像中的病变检测。但是，这种改进取决于要成像的对象的性质。具有结构的图像显示出改进的检测，而均匀的图像则没有。

BACKGROUND & AIMS: :Spin-echo phase images have been shown to be sensitive to blood flow and have been used to differentiate slow flow from thrombus, with an apparent advantage in comparison with spin-echo intensity images alone. In order to quantify the diagnostic efficacy of phase images, a study was performed comparing the sensitivity and specificity of MR imaging in identifying intravascular thrombus using spin-echo magnitude images alone and combined with phase images. In 45 subjects, 66 vessels with questionable intraluminal signal were reviewed in a blinded manner by four radiologists using seven levels of certitude for the diagnosis of thrombus. Vessels in the thorax, abdomen, and pelvis were included in the evaluation and were selected on the basis of the presence of intraluminal signal, which raised the possibility of intravascular disease. Corroborative studies were available in all cases. Receiver-operator-characteristic curves were constructed for the accuracy of the decision of intraluminal thrombus vs flow signal when using magnitude images alone and when using magnitude plus phase images. Magnitude images identified thrombus with a sensitivity of 35% at a specificity of 90%. On the other hand, combining magnitude image and phase images yielded sensitivities of 85% and 83% at specificities of 90% and 95%, respectively. We conclude that addition of phase images substantially increases the level of confidence in detecting intravascular thrombosis.

背景与目标： ：自旋回波相位图像已显示出对血流敏感，并已被用于区分血流和血流，与单独的自旋回波强度图像相比，具有明显的优势。为了量化相位图像的诊断功效，进行了一项研究，比较了单独使用自旋回波幅值图像并与相位图像结合使用MR成像在识别血管内血栓中的敏感性和特异性。在45名受试者中，四名放射科医生以七种程度的可信度以盲法方式检查了66个管腔内信号有问题的血管，以诊断血栓。评估中包括胸部，腹部和骨盆中的血管，并根据腔内信号的存在来选择血管，这增加了血管内疾病的可能性。在所有情况下都可以进行确证研究。当仅使用幅度图像和使用幅度加相位图像时，构造接收器-操作者特征曲线以决定腔内血栓与流量信号的精确度。大小图像以90％的特异性识别出35％的血栓。另一方面，将幅值图像和相位图像相结合，分别在90％和95％的特异性下可获得85％和83％的灵敏度。我们得出结论，相图像的添加大大增加了检测血管内血栓形成的置信度。

BACKGROUND & AIMS: :The complicated structure of fMRI signals and associated noise sources make it difficult to assess the validity of various steps involved in the statistical analysis of brain activation. Most methods used for fMRI analysis assume that observations are independent and that the noise can be treated as white gaussian noise. These assumptions are usually not true but it is difficult to assess how severely these assumptions are violated and what are their practical consequences. In this study a direct comparison is made between the power of various analytical methods used to detect activations, without reference to estimates of statistical significance. The statistics used in fMRI are treated as metrics designed to detect activations and are not interpreted probabilistically. The receiver operator characteristic (ROC) method is used to compare the efficacy of various steps in calculating an activation map in the study of a single subject based on optimizing the ratio of the number of detected activations to the number of false-positive findings. The main findings are as follows: Preprocessing. The removal of intensity drifts and high-pass filtering applied on the voxel time-course level is beneficial to the efficacy of analysis. Temporal normalization of the global image intensity, smoothing in the temporal domain, and low-pass filtering do not improve power of analysis. Choices of statistics. the cross-correlation coefficient and t-statistic, as well as nonparametric Mann-Whitney statistics, prove to be the most effective and are similar in performance, by our criterion. Task design. the proper design of task protocols is shown to be crucial. In an alternating block design the optimal block length is be approximately 18 s. Spatial clustering. an initial spatial smoothing of images is more efficient than cluster filtering of the statistical parametric activation maps.

背景与目标： ：fMRI信号的复杂结构和相关的噪声源使得难以评估参与大脑激活统计分析的各个步骤的有效性。用于功能磁共振成像分析的大多数方法都假定观察是独立的，并且可以将噪声视为高斯白噪声。这些假设通常是不正确的，但是很难评估这些假设被违反的严重程度以及它们的实际后果是什么。在本研究中，直接比较了用于检测激活的各种分析方法的功能，而没有参考统计显着性估计。功能磁共振成像中使用的统计数据被视为旨在检测激活的指标，并且没有概率解释。接收者操作员特征（ROC）方法用于基于优化检测到的激活次数与假阳性发现次数的比率，比较单个受试者研究中计算激活图的各个步骤的功效。主要发现如下：预处理。消除在体素时程级别上应用的强度漂移和高通滤波有助于提高分析效率。全局图像强度的时间标准化，时域平滑和低通滤波不能提高分析能力。统计选择。根据我们的标准，互相关系数和t统计量以及非参数Mann-Whitney统计量被证明是最有效的，并且在性能上相似。任务设计。任务协议的正确设计被证明是至关重要的。在交替模块设计中，最佳模块长度约为18 s。空间聚类。图像的初始空间平滑比统计参数激活图的聚类过滤更有效。

BACKGROUND & AIMS: :Receiver operating characteristic (ROC) analysis is well established in the evaluation of systems involving binary classification tasks. However, medical tests often require distinguishing among more than two diagnostic alternatives. The goal of this work was to develop an ROC analysis method for three-class classification tasks. Based on decision theory, we developed a method for three-class ROC analysis. In this method, the objects were classified by making the decision that provided the maximal utility relative to the other two. By making assumptions about the magnitudes of the relative utilities of incorrect decisions, we found a decision model that maximized the expected utility of the decisions when using log-likelihood ratios as decision variables. This decision model consists of a two-dimensional decision plane with log likelihood ratios as the axes and a decision structure that separates the plane into three regions. Moving the decision structure over the decision plane, which corresponds to moving the decision threshold in two-class ROC analysis, and computing the true class 1, 2, and 3 fractions defined a three-class ROC surface. We have shown that the resulting three-class ROC surface shares many features with the two-class ROC curve; i.e., using the log likelihood ratios as the decision variables results in maximal expected utility of the decisions, and the optimal operating point for a given diagnostic setting (set of relative utilities and disease prevalences) lies on the surface. The volume under the three-class surface (VUS) serves as a figure-of-merit to evaluate different data acquisition systems or image processing and reconstruction methods when the assumed utility constraints are relevant.

背景与目标： ：接收机工作特性（ROC）分析在涉及二进制分类任务的系统评估中已得到充分确立。但是，医学测试通常需要在两个以上的诊断替代方案之间进行区分。这项工作的目的是为三类分类任务开发一种ROC分析方法。基于决策理论，我们开发了一种用于三类ROC分析的方法。在此方法中，通过做出相对于其他两个对象提供最大效用的决策来对对象进行分类。通过对错误决策的相对效用的大小进行假设，我们发现了一个决策模型，当使用对数似然比作为决策变量时，该模型最大化了决策的预期效用。该决策模型由以对数似然比为轴的二维决策平面和将该平面分为三个区域的决策结构组成。在决策平面上移动决策结构，这相当于在两类ROC分析中移动决策阈值，并计算真实的1类，2类和3类分数定义了3类ROC曲面。我们已经表明，生成的三类ROC曲面与两类ROC曲线具有许多特征；即，使用对数似然比作为决策变量会导致决策的最大预期效用，并且给定诊断设置（相对效用和疾病患病率的集合）的最佳操作点位于表面。当假定的效用约束相关时，三级表面下的体积（VUS）可作为评估不同数据采集系统或图像处理和重构方法的一个品质因数。

BACKGROUND & AIMS: :Diagnostic or predictive accuracy concerns are common in all phases of a disease management (DM) programme, and ultimately play an influential role in the assessment of programme effectiveness. Areas, such as the identification of diseased patients, predictive modelling of future health status and costs and risk stratification, are just a few of the domains in which assessment of accuracy is beneficial, if not critical. The most commonly used analytical model for this purpose is the standard 2 x 2 table method in which sensitivity and specificity are calculated. However, there are several limitations to this approach, including the reliance on a single defined criterion or cut-off for determining a true-positive result, use of non-standardized measurement instruments and sensitivity to outcome prevalence. This paper introduces the receiver operator characteristic (ROC) analysis as a more appropriate and useful technique for assessing diagnostic and predictive accuracy in DM. Its advantages include; testing accuracy across the entire range of scores and thereby not requiring a predetermined cut-off point, easily examined visual and statistical comparisons across tests or scores, and independence from outcome prevalence. Therefore the implementation of ROC as an evaluation tool should be strongly considered in the various phases of a DM programme.

背景与目标： 诊断或预测准确性问题在疾病管理（DM）计划的所有阶段中都很常见，最终在评估计划有效性中起着重要作用。诸如疾病患者的识别，未来健康状况和成本的预测模型以及风险分层等领域只是对准确性进行评估（即使不是很重要）的几个领域。为此目的，最常用的分析模型是标准的2 x 2表格方法，在其中计算灵敏度和特异性。但是，这种方法存在一些局限性，包括依赖单个定义的标准或确定真实阳性结果的临界值，使用非标准化的测量工具以及对结果普遍性的敏感性。本文介绍了接收机操作员特征（ROC）分析，这是一种用于评估DM诊断和预测准确性的更合适和有用的技术。它的优点包括：整个评分范围内的测试准确性，因此不需要预定的临界点，可以轻松检查跨测试或评分的视觉和统计比较，并且不受结局患病率影响。因此，应在DM计划的各个阶段中强烈考虑将ROC用作评估工具。

BACKGROUND & AIMS: :ROC analysis has proved useful in assessing diagnostic efficiency. Large x-ray film series of thoracic images intended for cardiovascular diagnosis were used for studying diagnostic efficiency in relation to random sample size. Exploration of random samples from two classes of findings requiring diagnostic differentiation, with the same number of x-ray films in each class, showed satisfactory convergence between the radiologists' rating and the ROC curve if the size of the random sample groups was about 200 images each or larger. The smaller the random sample size (less than 200 images), the greater the scatter of the rating performance. In another series the rating ability of experienced radiologists was compared with that of a semi-automatic classificator. The semi-automatic classificator attained almost the same performance index as the low-performance evaluator.

背景与目标： ：ROC分析已证明对评估诊断效率有用。旨在进行心血管诊断的大型X射线胶片胸部图像被用于研究与随机样本量相关的诊断效率。在需要诊断差异的两类发现中探索随机样本，每类中具有相同数量的X射线胶片，如果随机样本组的大小约为200张图像，则放射线医师的评级和ROC曲线之间的收敛性令人满意每个或更大。随机样本大小越小（少于200张图像），评分性能的分散性就越大。在另一个系列中，将经验丰富的放射科医生的评级能力与半自动分类器的评级能力进行了比较。半自动分类器的性能指标几乎与低性能评估器相同。

BACKGROUND & AIMS: :This paper presents and evaluates a wavelet-based statistical analysis of PET images for the detection of brain activation areas. Brain regions showing significant activations were obtained by performing Student's t tests in the wavelet domain, reconstructing the final image from only those wavelet coefficients that passed the statistical test at a given significance level, and discarding artifacts introduced during the reconstruction process. Using Receiver Operating Characteristic (ROC) curves, we have compared this statistical analysis in the wavelet domain to the conventional image-domain Statistical Parametric Mapping (SPM) method. For obtaining an accurate assessment of sensitivity and specificity, we have simulated realistic single subject [15O]-H2O PET studies with different hyperactivation levels of the thalamic region. The results obtained from an ROC analysis show that the wavelet approach outperforms conventional SPM in identifying brain activation patterns. Using the wavelet method, activation areas detected were closer in size and shape to the region actually activated in the reference image.

背景与目标： ：本文介绍并评估了基于小波的PET图像统计分析，以检测大脑激活区域。通过在小波域中执行Student's t检验，仅根据在给定显着性水平下通过统计检验的那些小波系数重建最终图像，并丢弃在重建过程中引入的伪像，即可获得显示出明显激活作用的大脑区域。使用接收器工作特性（ROC）曲线，我们已经将小波域中的这种统计分析与常规的图像域统计参数映射（SPM）方法进行了比较。为了获得对敏感性和特异性的准确评估，我们模拟了具有不同丘脑区域高激活水平的现实单项[15O] -H2O PET研究。从ROC分析获得的结果表明，在识别大脑激活模式方面，小波方法优于传统的SPM。使用小波方法，检测到的激活区域的大小和形状更接近参考图像中实际激活的区域。