BACKGROUND & AIMS: PURPOSE:The aim of this article is to propose a quantitative methodology for determining a criterion to discriminate the nonsurgical nuclear cataract from the surgical one taking into account objective measures of intraocular scattering in patients with good visual acuity (>0.6). METHODS:Two groups of subjects were taken into account: a control group and a group with nuclear cataracts. At a first stage, eyes belonging to the cataract group were classified into "nonsurgical" and "surgical" cataracts by ophthalmologists at their clinical settings. At a second stage a double-pass instrument was also used to determine the objective scatter index (OSI) at the laboratory. Receiver operating characteristic (ROC) curves were used to analyze OSI values to determine a value able to separate between nonsurgical and surgical cataracts. RESULTS:We obtained statistically significant differences among the control and both nuclear cataract groups (p < 0.05). ROC curves determined an OSI criterion level (of 2.1) to suggest surgery in nuclear cataracts with an area under curve of 0.83, i.e. with 80% of sensitivity and 80% of specificity. CONCLUSIONS:ROC analysis allows separating both groups of nuclear cataract, and we determined a value of OSI in nuclear cataract quantification for surgery.

背景与目标： 目的：本文的目的是提出一种定量方法，用于确定将非手术性核性白内障与手术性白内障区别开来的标准，同时考虑到对具有良好视力（> 0.6）的患者眼内散射的客观测量。
方法：考虑两组受试者：对照组和患有核性白内障的组。在第一阶段，眼科医生在其临床环境中将属于白内障组的眼睛分为“非手术性”和“手术性”白内障。在第二阶段，还使用双通道仪器确定实验室的客观散射指数（OSI）。接收者操作特征（ROC）曲线用于分析OSI值，以确定能够在非手术性白内障和手术性白内障之间进行区分的值。
结果：我们在对照组和两个核性白内障组之间均获得了统计学上的显着差异（p <0.05）。 ROC曲线确定了OSI标准水平（为2.1），建议在核白内障下进行手术，其曲线下面积为0.83，即敏感性为80％，特异性为80％。
结论：ROC分析可将两组白内障分开，我们确定OSI在手术白内障定量中的价值。

BACKGROUND & AIMS: UNLABELLED:In the diagnosis of giant cell arteritis (GCA) with aortic involvement, (18)F-FDG PET has been demonstrated to be a powerful tool. No other imaging method is able to directly detect acute inflammation within the aortic wall. However, because GCA is a rare PET indication, the assessment of GCA with (18)F-FDG PET remains difficult and highly dependent on the experience of the investigator. This study aimed to semiquantify the relationship between aortic and liver uptake and to introduce a receiver operating characteristic (ROC)-based cutoff ratio to allow investigator- and experience-independent GCA diagnosis with optimal sensitivity and specificity. Ratios of aortic wall uptake versus liver uptake were calculated in a group of GCA patients and a control group. These data were assessed in an ROC analysis, and finally, a cutoff-ratio-optimizing strategy was applied. METHODS:Twenty-three patients with initially suspected GCA (18 positive for GCA criteria, 5 negative) and 36 matched controls were included. The control subjects underwent PET for oncologic diagnostics. None had intrathoracic or hepatic disease or therapy-related tracer accumulation. Additionally, physiologic liver metabolism was ensured by the presence of normal liver enzymes. After defining regions of interest over the thoracic aorta and the liver, we calculated maximal standardized uptake value ratios. Sensitivities and specificities for cutoff ratios from 0.1 to 2.5 were estimated and were ultimately used to assess an optimal cutoff ratio for separating GCA patients from controls. To further investigate the usefulness of the resulting cutoff ratio, we tested it in a second control group with changed hepatic metabolism and elevated liver enzymes. RESULTS:ROC analysis revealed optimal selectivity for a cutoff ratio of 1.0. This ratio led to a sensitivity of 88.9%, a specificity of 95.1%, and an accuracy of 94.4%. When this aorta-to-liver ratio was applied to the control group with pathologic liver metabolism, the resulting specificity was 95.6%. CONCLUSION:The (18)F-FDG PET region-of-interest analysis with aorta-to-liver maximal standardized uptake value ratios is a reliable, investigator-independent indicator of GCA not affected by minor inflammation-associated changes in hepatic metabolism. Our results for a cutoff ratio of 1.0 prove that (18)F-FDG PET is a method of high sensitivity and specificity for GCA-related large-vessel inflammation.

背景与目标： 引爆标签：在诊断主动脉受累的巨细胞动脉炎（GCA）中，已证明（18）F-FDG PET是一种强大的工具。没有其他成像方法能够直接检测主动脉壁内的急性炎症。但是，由于GCA是一种罕见的PET适应症，因此用（18）F-FDG PET进行GCA评估仍然很困难，并且高度依赖于研究者的经验。这项研究旨在半定量主动脉和肝脏摄取之间的关系，并引入基于受体工作特征（ROC）的截留比，以使研究者和经验独立的GCA诊断具有最佳的敏感性和特异性。计算了一组GCA患者和对照组的主动脉壁摄取与肝脏摄取的比率。这些数据在ROC分析中进行了评估，最后，采用了截止比例优化策略。
方法：包括23例最初怀疑为GCA的患者（GCA标准为18例阳性，5例阴性）和36例匹配的对照组。对照组接受PET进行肿瘤诊断。没有人有胸内或肝病或与治疗有关的示踪剂蓄积。另外，正常肝酶的存在确保了生理肝的新陈代谢。在定义了胸主动脉和肝脏的目标区域后，我们计算了最大标准化摄取值比率。估计了截留比从0.1到2.5的敏感性和特异性，并最终用于评估将GCA患者与对照组分开的最佳截留比。为了进一步研究所得截留比的有用性，我们在肝代谢改变和肝酶升高的第二个对照组中进行了测试。
结果：ROC分析显示最佳的选择性为1.0的截止值。该比率导致灵敏度为88.9％，特异性为95.1％和准确度为94.4％。当将该主动脉与肝脏的比率应用于具有病理性肝代谢的对照组时，所产生的特异性为95.6％。
结论：（18）F-FDG PET感兴趣的区域分析具有主动脉-肝脏最大标准化摄取值比是一种可靠的，独立于研究者的指示性GCA指标，不受肝脏炎症相关的微小变化影响。我们的截留比为1.0的结果证明（18）F-FDG PET是一种针对GCA相关的大血管炎症的高灵敏度和特异性方法。

BACKGROUND & AIMS: RATIONALE AND OBJECTIVES:Several authors have encouraged the use of a quasi-continuous rating scale for data collection in receiver operating characteristic (ROC) curve analysis of diagnostic modalities, rather than rating scales based on five to seven ordinal categories or levels of suspicion. Although many investigators have gone over to this method, a discussion of the issues continues. The present work provides a quantitative analysis from the viewpoint of measurement science. MATERIALS AND METHODS:A simple model of the effect of data discretization or quantization on the measurement of the variance of noisy data was developed. Then Monte Carlo simulations of multiple-reader, multiple-case ROC experiments were performed and analyzed in terms of components-of-variance models to investigate the effect of data quantization in that more complex setting. RESULTS:For single-reader studies, discretization into five categories can reduce the precision of ROC measurements by a large amount. The effect may be attenuated in multireader studies. CONCLUSION:More precise measurements of diagnostic detection performance and thus more efficient use of resources are served by good measurement methods. These are promoted by the use of a quasi-continuous rating scale in ROC studies.

背景与目标： 理由和目标：几位作者鼓励在诊断模式的接收器工作特征（ROC）曲线分析中使用准连续评分量表进行数据收集，而不是基于五到七个序数类别或可疑程度的评分量表。尽管许多研究人员已经采用了这种方法，但有关问题的讨论仍在继续。本工作从测量科学的角度提供了定量分析。
材料与方法：建立了数据离散化或量化对噪声数据方差测量的影响的简单模型。然后，对多阅读器，多案例ROC实验进行了蒙特卡洛模拟，并根据方差分量模型进行了分析，以研究在更复杂的环境中数据量化的效果。
结果：对于单阅读器研究，离散化为五类可能会大大降低ROC测量的精度。在多阅读器研究中，这种作用可能会减弱。
结论：良好的测量方法可对诊断检测性能进行更精确的测量，从而更有效地利用资源。通过在ROC研究中使用准连续评分量表可以促进这些目的。

BACKGROUND & AIMS: :Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis function is associated with suicidal behavior. In suicide attempters with mood disorder, the non-suppressor status in the dexamethasone suppression test (DST) is associated with suicide indicating that HPA-axis hyperactivity is a biological risk factor for suicide and may be a useful predictor. The threshold of 5 microg/dl for cortisol levels measured at 08:00 a.m. or 4:00 p.m. following dexamethasone at 11:00 p.m. to define the DTS nonsuppression was derived as being optimal for the separation of melancholia and nonmelancholic conditions rather than the prediction of suicide. A different threshold may offer a better identification of suicide. The aim of this study was to find the optimal threshold level of post DST plasma cortisol at 4 p.m. for suicide prediction using receiver operating characteristics (ROC) analysis. A cohort of 106 depressed inpatients with an index suicide attempt admitted to the department of Psychiatry at the Karolinska University Hospital between 1980 and 2000, were submitted to DST and followed up for causes of death. During the follow-up (mean 17 years), 25 suicides (24%) were identified. The ROC analysis revealed that a lower threshold of 3.3 microg/dl for the nonsuppressor status predicted 17 of 25 suicides (sensitivity of 68%) compared with 15 of 25 suicides (sensitivity 60%) with a conventional threshold of 5 microg/dl at 4:00 p.m. In male suicide attempters the lower threshold for pathological DST result (3.3 microg/dl) changed the Odds ratio from 6.7 till 18. In female suicide attempters a higher threshold (7.3 microg/dl) optimised the value of DST as a biological test for suicide prediction indicating a gender difference.

背景与目标： ：下丘脑-垂体-肾上腺（HPA）轴功能失调与自杀行为有关。在患有情绪障碍的自杀未遂者中，地塞米松抑制试验（DST）中的非抑制状态与自杀有关，表明HPA轴过度活跃是自杀的生物学危险因素，可能是有用的预测因子。在上午08:00或下午4:00测量的皮质醇水平的阈值为5 microg / dl。晚上11:00进行地塞米松治疗后定义DTS的非抑制作用是分离忧郁症和非忧郁症疾病而不是自杀预测的最佳方法。不同的阈值可以更好地识别自杀。这项研究的目的是在下午4点找到DST后血浆皮质醇的最佳阈值水平。使用接收者工作特征（ROC）分析进行自杀预测。 1980年至2000年之间，卡罗林斯卡大学医院精神病科收治的106名抑郁指数低企的住院患者被送往DST，并就其死因进行了随访。在随访期间（平均17年），确定了25例自杀（占24％）。 ROC分析显示，非抑制状态的较低阈值3.3 microg / dl预测25种自杀中的17种（敏感性为68％），而25种自杀状态中有15种自杀（敏感性60％）在4下常规阈值为5 microg / dl ：00 pm在男性自杀未遂中，病理性DST结果的较低阈值（3.3 microg / dl）将比值比从6.7更改为18。在女性自杀未遂中，较高的阈值（7.3 microg / dl）优化了DST值作为自杀的生物学测试表示性别差异的预测。

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。