Phenotypic and genotypic heterogeneity in gaucher disease: Implications for genetic counseling

Genetic counseling for Gaucher disease is complicated by the vast degree of clinical heterogeneity encountered in the disorder. Recent advances in our understanding of the molecular genetics of Gaucher disease are particularly relevant to genetic counseling. Although the identification of mutations in the glucocerebrosidase gene has enabled genotypic screening of Gaucher patients, the ability to reliably predict patient outcome on the basis of DNA studies is often limited. An appreciation of both the spectrum of clinical manifestations in Gaucher patients and the limitations of the available genotypic information is necessary when counseling patients, families and at-risk individuals.     

Fisher transformations for correlations corrected for selection and missing data

The validity of a test is often estimated in a nonrandom sample of selected individuals. To accurately estimate the relation between the predictor and the criterion we correct this correlation for range restriction. Unfortunately, this corrected correlation cannot be transformed using Fisher'sZ transformation, and asymptotic tests of hypotheses based on small or moderate samples are not accurate. We developed a Fisherr toZ transformation for the corrected correlation for each of two conditions: (a) the criterion data were missing due to selection on the predictor (the missing data were MAR); and (b) the criterion was missing at random, not due to selection (the missing data were MCAR). The twoZ transformations were evaluated in a computer simulation. The transformations were accurate, and tests of hypotheses and confidence intervals based on the transformations were superior to those that were not based on the transformations.     

Some properties of two measures of multivariate association

Two kinds of measures of multivariate association, based on Wilks' and the Bartlett-Nanda-Pillai trace criterionV, respectively, are compared in terms of properties of the univariateR ² which they generalize. A unified set of derivations of the properties is provided which are self-contained and not restricted to decompositions in canonical variates. One conclusion is that asymmetric index based on allows generalization of the multiplicative decomposition ofR ² in terms of squared partial correlations, but not the additive decomposition in terms of squared semipartial correlations, while the reverse is true for anasymmetric index based onV.We are indebted to Jos M. F. ten Berge for some fruitful discussions.     

Some effects of response-correlated increases in reinforcer magnitude on human behavior

After training under short or long fixed-interval schedules, humans responded under a modified fixed-interval schedule in which magnitude of reinforcement (X or 2X) was minimally correlated with response frequency. Response frequencies that equaled or exceeded a minimum response criterion were followed by the larger reinforcer at the end of the interval; otherwise, the smaller reinforcer was delivered. The modified schedule alternated with the baseline schedule across conditions. In a control condition, the reinforcer magnitudes produced by control subjects were yoked to those of experimental subjects. Experimental subjects, but not control subjects, showed increased responding. In addition to the baseline and modified fixed-interval schedules used in Experiment 1, subjects in Experiment 2 also responded under a second modified fixed-interval contingency in which increases in reinforcer magnitude were more highly correlated with response frequency. Experimental subjects, but not control subjects, showed increased responding under both procedures. Direct comparison of these two procedures showed that the high-correlation procedure produced greater increases in responding than did the low-correlation procedure.     

不同年龄妇科患者痛阈测试及其临床意义

采用双盲、前瞻性研究,选择90例妇科择期全麻下子宫肌瘤剔除或子宫全切手术患者,ASA分级Ⅰ或Ⅱ级,按年龄分两组,中青年组（A组）50例,年龄25岁～50岁,老年组（B组）40例,年龄60岁-80岁,术前使用电刺激测定并记录患者的痛阈和耐痛阈,观察不同年龄妇科患者痛阈和耐痛阈以及两者之间相关性。结果显示A组与B组痛阈分别为（1．86±0．51）mA和（1．89±0．66）mA差异无统计学意义;A组比B组耐痛阈低分别为（6．16±2．53）mA和（8．40士3．21）mA,差异有统计学意史;A组痛阈与耐痛阈之间有相关性（Spearman相关系数为-0．42,P〈0．05）;B组痛阈与耐痛阈之间无相关性。因此,老年患者耐痛阈升高,中青年患者术前痛阈和耐痛闽均可预测术后疼痛,老年患者术前痛阈不能预测术后疼痛。     

大数据时代背景下的医学思考*--转化医学新趋势前瞻

作为21世纪最具活力的医学发展模式,转化医学为基础和临床构建了交流沟通的高效平台,当前正朝着多学科、多领域、多系统的方向迈进。随着信息技术与生命科学的交叉融合,生物医学已经迈入大数据时代。大数据既保证了医学实践的深度,有深度才能洞悉本质;又保证了医学实践的高度,有高度才能总揽全局。因此,大数据的出现为深陷还原论泥潭的现代医学提供了有效的解决途径。大数据浪潮对医学基础研究和医疗实践的深远影响,必将为转化医学发展带来新的发展机遇。     

Aggregating to the between-person level in idiographic research designs: Personal goal research as an example of the need to distinguish between reliability and homogeneity

In several areas of personality research (e.g., personal networks, interpersonal behaviour, academic effort), the empirical data represent a multilevel structure, in which within-person variables are nested within individuals. Both within-person variation and between-person differences can be related to outcome variables (e.g., emotions, life satisfaction). One major precondition for aggregating within-person data to the between-person level is sufficient reliability of the aggregated data, a point that has received scant attention in previous research. Drawing on the example of personal goal research, we recommend that the two major forms of the intraclass correlation coefficient—the ICC(1) and the ICC(2)—be applied to within-person data in idiographic research designs. These indices allow the homogeneity and reliability of within-person data to be determined separately. Their application is illustrated using data from a study with 4,565 young adults.     

采用理想点方法检验生活取向测验及其修订版的单维性

该文从项目反应过程出发,认为可能是由于原有的维度分析方法将生活取向测验（LOT）及其修订版（LOT-R）这两个测验的项目反应理想点过程错误地限定为优势过程,导致两个测验违背单维性的结论;进而采用主成分分析的未旋转成分负荷散点图和对应分析的维度分数散点图,并结合项目相关矩阵法验证LOT和LOT-R的维度。结果显示LOT-R的单维性得到了验证,LOT由于包含两个测量应对的项目而导致违背单维性。最后作者提出应该与理想点过程相一致的心理计量学模型对LOT-R的数据进行分析。     

A note on moran's measure of multiple rank correlation

A measure of multiple rank correlation,T _y.12 ², is proposed for the situation with no tied observations in the variables. The measure is a weighted average of two squared Kendall taus. It is shown thatT _y.12 ² is equivalent to a statistic previously proposed by Moran and thus a new interpretation is given to Moran's statistic.The author wishes to thank Nancy Anderson, Willard Larkin, and Kent Norman for their helpful comments.     

Influence in canonical correlation analysis

The perturbation theory of the generalized eigenproblem is used to derive influence functions of each squared canonical correlation coefficient and the corresponding canonical vector pair. Three sample versions of these functions are described and some properties are noted. As particular applications, the influence function of the squared multiple correlation coefficient and influence functions of eigenvalues and eigenvectors in correspondence analysis are obtained. Three numerical examples are briefly discussed.We thank the Editor and the anonymous reviewers for their helpful comments. This research was carried out with the financial support of the Italian Ministry of the University and the National Research Council.