Assessing the skill of yes/no predictions

Summary Should healthy, middle‐aged women receive precautionary mammograms? Should trauma surgeons use the popular TRISS score to predict the likelihood of patient survival? These are examples of questions confronting us when we decide whether to use a yes/no prediction. In order to trust a prediction we must show that it is more valuable than would be our best guess of the future in the absence of the prediction. Calculating value means identifying our loss should the prediction err and examining the past performance of the prediction with respect to that loss. A statistical test to do this is developed. Predictions that pass this test are said to have skill. Only skillful predictions should be used. Graphical and numerical methods to identify skill will be demonstrated. The usefulness of mammograms is explored.     

Correlation of protein expression, Gleason score and DNA ploidy in prostate cancer

The prognosis of prostate cancer correlates with tumor differentiation. Gleason score and DNA ploidy are two prognostic factors that correlate with prognosis. We analyzed differences in protein expression in prostate cancer of high and low aggressiveness according to these measures. From 35 prostatectomy specimens, 29 cancer samples and 10 benign samples were harvested by scraping cells from cut surfaces. DNA ploidy was assessed by image cytometry. Protein preparations from cell suspensions were examined by 2-DE. Protein spots that differed quantitatively between sample groups were identified by MS fingerprinting of tryptic fragments and MS/MS sequence analysis. We found 39 protein spots with expression levels that were raised or lowered in correlation with Gleason score and/or DNA ploidy pattern (31 overexpressed in high-malignant cancer, 8 underexpressed). Of these, 30 were identified by MS. Among overexpressed proteins were heat-shock, structural and membrane proteins and enzymes involved in gene silencing, protein synthesis/degradation, mitochondrial protein import (metaxin 2), detoxification (GST-pi) and energy metabolism. Stroma-associated proteins were generally underexpressed. The protein expression of prostate cancer correlates with tumor differentiation. Potential prognostic markers may be found among proteins that are differentially expressed and the clinical value of these should be validated.     

老年冠心病患者血清Lp-PLA2、hs-CRP、IL-27及MMP-9水平与Gensini积分的相关性研究*

目的:探讨老年冠心病患者血清脂蛋白相关磷脂酶A2(Lp-PLA2)、高敏C反应蛋白(hs-CRP)、白细胞介素-27(IL-27)及基质金属蛋白酶-9(MMP-9)水平与Gensini积分的相关性。方法:选取2015年10月至2018年2月我院收治的冠心病患者142例为研究对象,将所有患者按照不同的冠心病类型分为不稳定型心绞痛(UAP)组54例、稳定型心绞痛(SAP)组40例和急性心肌梗死(AMI)组48例。同时根据患者Gensini积分将其分为轻度47例、中度51例和重度44例。比较不同冠心病类型、不同严重程度的Lp-PLA2、hs-CRP、IL-27、MMP-9水平及Gensini积分,并分析冠心病患者上述指标水平与Gensini积分的相关性。结果:AMI组患者Lp-PLA2、hs-CRP、IL-27、MMP-9水平及Gensini积分均高于UAP组和SAP组,且UAP组高于SAP组(P0.05)。重度患者Lp-PLA2、hs-CRP、IL-27、MMP-9水平及Gensini积分均高于中度和轻度患者,且中度患者高于轻度患者(P0.05)。经Spearman相关性分析结果显示,冠心病患者Lp-PLA2、hs-CRP、IL-27、MMP-9水平与Gensini积分均呈正相关(P0.05)。结论:老年冠心病患者Lp-PLA2、hs-CRP、IL-27及MMP-9水平与患者冠状动脉病变Gensini积分均呈正相关。临床根据Lp-PLA2、hs-CRP、IL-27及MMP-9水平的变化,有助于评估老年冠心病患者的病情严重程度。     

Model misspecification and bias for inverse probability weighting estimators of average causal effects

Commonly used semiparametric estimators of causal effects specify parametric models for the propensity score (PS) and the conditional outcome. An example is an augmented inverse probability weighting (IPW) estimator, frequently referred to as a doubly robust estimator, because it is consistent if at least one of the two models is correctly specified. However, in many observational studies, the role of the parametric models is often not to provide a representation of the data-generating process but rather to facilitate the adjustment for confounding, making the assumption of at least one true model unlikely to hold. In this paper, we propose a crude analytical approach to study the large-sample bias of estimators when the models are assumed to be approximations of the data-generating process, namely, when all models are misspecified. We apply our approach to three prototypical estimators of the average causal effect, two IPW estimators, using a misspecified PS model, and an augmented IPW (AIPW) estimator, using misspecified models for the outcome regression (OR) and the PS. For the two IPW estimators, we show that normalization, in addition to having a smaller variance, also offers some protection against bias due to model misspecification. To analyze the question of when the use of two misspecified models is better than one we derive necessary and sufficient conditions for when the AIPW estimator has a smaller bias than a simple IPW estimator and when it has a smaller bias than an IPW estimator with normalized weights. If the misspecification of the outcome model is moderate, the comparisons of the biases of the IPW and AIPW estimators show that the AIPW estimator has a smaller bias than the IPW estimators. However, all biases include a scaling with the PS-model error and we suggest caution in modeling the PS whenever such a model is involved. For numerical and finite sample illustrations, we include three simulation studies and corresponding approximations of the large-sample biases. In a dataset from the National Health and Nutrition Examination Survey, we estimate the effect of smoking on blood lead levels.     

冠心病患者血浆CD69、DKK-1与血脂、炎性因子的关系及其诊断价值分析

摘要 目的：分析冠心病（CHD）患者血浆CD69、Wnt拮抗剂蛋白-1（DKK-1）与血脂、炎性因子的关系,并分析CD69和DKK1对于CHD患者的诊断价值。方法：选取2016年6月~2018年12月在我院诊治的CHD患者136例,根据Gensini评分分为轻度亚组、中度亚组、重度亚组,同时纳入与之年龄、性别匹配的冠状动脉造影正常者136例作为对照组。检测受试者血清炎性因子、血脂、及血浆CD69、DKK-1水平,分析CHD患者CD69、DKK-1水平与血脂、炎性因子、Gensini评分的相关性,采用受试者工作特征（ROC）曲线分析CD69和DKK1对于CHD患者的诊断价值。结果：CHD患者CD69、DKK-1、白细胞介素-10（IL-10)、白细胞介素-6（IL-6）、三酰甘油（TG）、总胆固醇（TC）、低密度脂蛋白（LDL）水平高于对照组,高密度脂蛋白（HDL）水平低于对照组（P<0.05）;随着冠脉狭窄病变程度的加重,CD69、DKK-1、IL-10、IL-6、TC、TG、LDL水平呈升高趋势,HDL水平呈降低趋势（P<0.05）。CHD患者CD69、DKK-1水平与IL-10、IL-6、TC、TG、LDL、Gensini评分均呈正相关,与HDL呈负相关（P<0.05）。ROC曲线分析结果显示,CD69、DKK-1联合检测诊断CHD的灵敏度、特异度分别为0.816、0.846。结论：CHD患者血浆DKK-1、CD69水平升高,与血脂、炎性因子和Gensini评分密切相关,两者联合检测可提高CHD诊断效能。     

血清IgE水平与冠心病的相关性分析

目的:探讨血清IgE水平与冠心病的相关性。方法:将我院收治的135例患者根据冠脉造影结果分为冠心病组(CHD)和非冠心病组(non-CHD),冠心病组根据临床症状分为稳定型心绞痛组(SAP)、不稳定型心绞痛组(UAP)和急性心肌梗死组(AMI),动脉堵塞程度用Gensini评分量化,采用SIMENS BNII全自动免疫散射比浊仪测定总IgE水平。比较CHD和non-CHD组患者及SAP、UAP和AMI组患者血清IgE水平的差异,并进一步分析血清IgE等级与冠心病Gensini积分的相关性。结果:non-CHD患者血清IgE水平(32.3(13.5,61)KU/L)明显低于CHD患者(69(26.4,169)KU/L)(P=0.001),UAP和AMI患者血清IgE水平(78.6(37.0,191.0)KU/L、118.5(75.3,148.1)KU/L)均显著高于SAP组(36.7(20.7,96.7)KU/L)(P=0.034和P=0.001),且多支血病变组患者血清IgE水平(67.2(30.9,249.0)KU/L)显著高于单支血管病变患者(34.6(18.1,59.0)KU/L)(P=0.039)。IgE水平根据四分位间距分为四个等级,随着IgE分级水平增加冠心病Gensini积分增加。结论:冠心病患者血清IgE水平升高,且与冠心病类型和血管堵塞程度都存在显著相关性,可能辅助冠心病的诊断及病情监测。     

Convergence to Normality of the Asymptotic Quasi‐Score Function on a Linear Model

The asymptotic quasi‐likelihood method is considered for the model y_t = f_t(θ) + M_t, t = 0,1, …,T where f_tθ) is a linear predictable process of the parameter of interest θ, M_t is a martingale difference, and the nature of E(M_t² | ℱ_t–1) is unknown. This paper is concerned with the limiting distribution of the asymptotic quasi‐score function of such a model. Confidence intervals and hypothesis testing of θ is derived from the limiting distribution. Comparison is made between the estimates obtained through this method and those obtained through the least squares method.