The dilemma of negative analysis of variance estimators of intraclass correlation

Summary At least two common practices exist when a negative variance component estimate is obtained, either setting it to zero or not reporting the estimate. The consequences of these practices are investigated in the context of the intraclass correlation estimation in terms of bias, variance and mean squared error (MSE). For the one-way analysis of variance random effects model and its extension to the common correlation model, we compare five estimators: analysis of variance (ANOVA), concentrated ANOVA, truncated ANOVA and two maximum likelihood-like (ML) estimators. For the balanced case, the exact bias and MSE are calculated via numerical integration of the exact sample distributions, while a Monte Carlo simulation study is conducted for the unbalanced case. The results indicate that the ANOVA estimator performs well except for designs with family size n = 2. The two ML estimators are generally poor, and the concentrated and truncated ANOVA estimators have some advantages over the ANOVA in terms of MSE. However, the large biases may make the concentrated and truncated ANOVA estimators objectionable when intraclass correlation () is small. Bias should be a concern when a pooled estimate is obtained from the literature since <0.05 in many genetic studies.     

Bias of maximum likelihood estimator of intraclass correlation

Summary A bias correction was derived for the maximum likelihood estimator (MLE) of the intraclass correlation. The bias consisted of two parts: a correction from MLE to the analysis of variance estimator (ANOVA) and the bias of ANOVA. The total possible bias was always negative and depended upon both the degree of correlation and the design size and balance. The first part of the bias was an exact algebraic expression from MLE to ANOVA, and the corrected estimator by this part was ANOVA. It was also shown that the first correction term was equivalent to Fisher's reciprocal bias correction on hisZ scores. The total possible bias of MLE was large for small and moderate samples. Relative biases were larger for small parametric values and vice versa. To ensure a relative bias less than 10% assuming an intraclass correlation of 0.025, which is not unusual in most of the animal genetic studies, the total number of observations (N) should be not less than 500. From a design point of view, minimum bias occurred atn = 2, the minimum family size possible, underN fixed.     

Comparison of recent estimators of interclass correlation from familial data

The asymptotic and finite-sample properties of several recent estimators of interclass correlation are compared to more traditional estimators in the case of a variable number of siblings per family. It is shown that Karlin's family-weighted pairwise estimator (Karlin, Cameron, and Williams, 1981, Proceedings of the National Academy of Science 78, 2664-2668) is virtually equivalent to the ensemble estimator (Rosner, Donner, and Hennekens, 1977, Applied Statistics 26, 179-187), thus suggesting an estimator of the former's asymptotic variance. Further, an estimator proposed by Srivastava (1984, Biometrika 71, 177-185) is shown to be identical to the modified sib-mean estimator (Konishi, 1982, Annals of the Institute of Statistical Mathematics 34, 505-515) when the sib-sib correlation is estimated by the method of unweighted group means. Although the estimator due to Srivastava has smaller asymptotic variance than the other two, the gain in efficiency is slight, for familial data, both asymptotically and in finite samples.     

The relationship between force and focal complex development

To adhere and migrate, cells must be capable of applying cytoskeletal force to the extracellular matrix (ECM) through integrin receptors. However, it is unclear if connections between integrins and the ECM are immediately capable of transducing cytoskeletal contraction into migration force, or whether engagement of force transmission requires maturation of the adhesion. Here, we show that initial integrin-ECM adhesions become capable of exerting migration force with the recruitment of vinculin, a marker for focal complexes, which are precursors of focal adhesions. We are able to induce the development of focal complexes by the application of mechanical force to fibronectin receptors from inside or outside the cell, and we are able to extend focal complex formation to vitronectin receptors by the removal of c-Src. These results indicate that cells use mechanical force as a signal to strengthen initial integrin-ECM adhesions into focal complexes and regulate the amount of migration force applied to individual adhesions at localized regions of the advancing lamella.     

Quantifying test-retest reliability using the intraclass correlation coefficient and the SEM

Reliability, the consistency of a test or measurement, is frequently quantified in the movement sciences literature. A common metric is the intraclass correlation coefficient (ICC). In addition, the SEM, which can be calculated from the ICC, is also frequently reported in reliability studies. However, there are several versions of the ICC, and confusion exists in the movement sciences regarding which ICC to use. Further, the utility of the SEM is not fully appreciated. In this review, the basics of classic reliability theory are addressed in the context of choosing and interpreting an ICC. The primary distinction between ICC equations is argued to be one concerning the inclusion (equations 2,1 and 2,k) or exclusion (equations 3,1 and 3,k) of systematic error in the denominator of the ICC equation. Inferential tests of mean differences, which are performed in the process of deriving the necessary variance components for the calculation of ICC values, are useful to determine if systematic error is present. If so, the measurement schedule should be modified (removing trials where learning and/or fatigue effects are present) to remove systematic error, and ICC equations that only consider random error may be safely used. The use of ICC values is discussed in the context of estimating the effects of measurement error on sample size, statistical power, and correlation attenuation. Finally, calculation and application of the SEM are discussed. It is shown how the SEM and its variants can be used to construct confidence intervals for individual scores and to determine the minimal difference needed to be exhibited for one to be confident that a true change in performance of an individual has occurred.     

The relationship between human cytomegalovirus infection and atherosclerosis development

Transport characteristics of essential trace elements as zinc, copper, selenium and iron have been studied in maternal–fetal direction in normal pregnancies, using in vitro perfusion of human placental lobules. Solutions of trace elements corresponding to twice the physiological concentrations were injected (100 l bolus) into the maternal arterial perfusate. Serial perfusate samples were collected every 30 sec from venous outflows for a study period of 5 min. Concentrations of these trace elements and their transport kinetics were determined. Transport fractions (TF) of zinc, copper, selenium and iron averaged 0.21, 0.49, 0.55 and 0.10% of maternal load respectively. Other parameters such as area under the curve, clearance, elimination constant, absorption and elimination rates showed some significant differences between the various elements. Copper and selenium appear to be transported passively in maternal–fetal direction, while for iron and zinc, role of active transport for transfer across the human placental membrane cannot be discounted. We speculate that alterations in copper: zinc TR50 (transport rate for 50% efflux) and TF ratios could serve as useful indicators for assessing placental transport status of these essential elements in complicated pregnancy states.     

A comparison of confidence interval methods for the intraclass correlation coefficient

Different methods of obtaining confidence intervals for the intraclass correlation coefficient rho in the unbalanced one-way random-effects model are investigated, focusing on applications to family studies. Methods based on simple modifications of formulas for the case of equal group sizes are found to provide adequate coverage at small to moderate values of rho. A method based on the large-sample standard error of the sample intraclass correlation, as derived by Smith (1956, Annals of Human Genetics 21, 363-373), is shown to provide consistently good coverage at all values of rho. A method proposed by Thomas and Hultquist (1978, Annals of Statistics 6, 582-587) also provides consistently good coverage, but generates mean interval widths substantially greater than those generated by Smith's method at values of rho likely to arise in practice.     

The relationship between leaf canopy development and yield of barley

A study was carried out into the relationship between sowing date, canopy development and yield of four barley genotypes sown in autumn and spring. Yield was considered as the product of PAR absorbed by the crop canopy up till anthesis, the dry matter: radiation quotient, the ratio of grains m²at maturity to the weight of the crop at anthesis and the mean grain weight. Equations were derived to predict the time course of the proportion of PAR absorbed in relation to date of sowing using thermal time as predictor. In crops that were not short of water and were fully vernalised, genotypic differences were detected in plant population density, date of anthesis, and the four yield components identified above. All attributes except plant population density were affected by shortage of water but genotypes differed in their response.     

The correlation between oxidative stress and leaf senescence during plant development

In plants, besides being the final step leading to the death of the whole organism, senescence has a developmental function involving the coordinated degradation of macromolecules and the mobilization of nutrients out of senescing tissues into developing parts of the plant. Free radicals are thought to play an essential role in senescence, especially those derived from oxygen. Since these molecules are extremely toxic, the levels of the different reactive oxygen species have to be tightly regulated. However, at low concentrations, hydrogen peroxide may also serve as a signalling molecule. Therefore, a coordinated regulation of the free radical scavenging system, which comprises enzymatic components such as catalase, superoxide dismutase and ascorbate peroxidase, and non-enzymatic molecules such as ascorbate and glutathione is essential. The increased radical levels displayed during senescence are not only caused by the elevated production of radicals but also by a loss in antioxidant capacity.     

The functional relationship between feeding type and jaw and cranial morphology in ungulates

The relationship between jaw and skull morphology and feeding type (grazer, mixed feeder, browser, frugivorous, omnivorous) was analysed in 94 species of extant ungulates. A total of 21 morphological traits of the jaw and skull (17 and 4, respectively) were analysed using analysis of covariance, with body mass as covariate. To take into account the phylogenetic effect, simulations were generated under the Brownian motion model of character evolution. Analysis of covariance was applied to these simulations and the simulated F-ratios were used to assess the signification of the F-ratios for the real values of the traits. The feeding types had a weak effect on ungulate cranial and jaw morphology in comparison with the phylogenetic effect, since, before phylogeny correction, the analysis of covariance showed statistically significant differences associated with feeding type in 15 out of the 21 traits analysed. After controlling for phylogeny, only 2 significant traits remained, the length of the coronoid process and the occipital height. Omnivorous species had shorter coronoid processes than grazers or mixed feeders, and the occipital height was greater in the omnivorous species than in the grazers, mixed feeders or browsers. The coronoid process is involved in the generation of bite force, being the effective moment arm of the temporalis muscle, and occipital height is positively related to the force exerted by the temporalis muscle. This result matches the hypothesis that species with a toughness diet should show higher bite force (“toughness” describes the resistance of a material to being mechanically broken down). When the omnivorous species were excluded from the analysis, no differences in jaw and skull morphology were detected between the rest of the feeding types. Received: 1 September 1998 / Accepted: 2 November 1998     

Macronutrients mediate the functional relationship between Drosophila and Wolbachia

Wolbachia are maternally inherited bacterial endosymbionts that naturally infect a diverse array of arthropods. They are primarily known for their manipulation of host reproductive biology, and recently, infections with Wolbachia have been proposed as a new strategy for controlling insect vectors and subsequent human-transmissible diseases. Yet, Wolbachia abundance has been shown to vary greatly between individuals and the magnitude of the effects of infection on host life-history traits and protection against infection is correlated to within-host Wolbachia abundance. It is therefore essential to better understand the factors that modulate Wolbachia abundance and effects on host fitness. Nutrition is known to be one of the most important mediators of host–symbiont interactions. Here, we used nutritional geometry to quantify the role of macronutrients on insect–Wolbachia relationships in Drosophila melanogaster. Our results show fundamental interactions between diet composition, host diet selection, Wolbachia abundance and effects on host lifespan and fecundity. The results and methods described here open a new avenue in the study of insect–Wolbachia relationships and are of general interest to numerous research disciplines, ranging from nutrition and life-history theory to public health.     

促卵泡成熟激素受体与卵巢癌发生发展的关系研究进展

近年来促性腺激素及其受体与卵巢癌的关系研究受到人们的广泛关注,目前已在基础性研究和流行病学调查方面取得了巨大的进展.在体内和体外模型中都已证实,作为促性腺激素成分之一的促卵泡成熟激素通过其受体对卵巢上皮细胞的细胞增殖、凋亡、细胞粘附、侵袭和转移等生物学功能发挥了重要影响.这些研究证明了促卵泡成熟激素受体和卵巢癌的发生发展密切相关,它不但增强卵巢肿瘤细胞的增殖活性,还激活多种信号通路,促进肿瘤细胞的侵袭和转移能力;促卵泡成熟激素受体的脱敏化可能是卵巢癌发生的重要分子机制;从基因水平上,其多态性还与卵巢癌的易感性密切相关;由于它介导上皮性卵巢癌的多种恶性生物功能,因此,它是一个潜在的抗卵巢癌治疗的重要靶标.虽然如此,但是卵巢癌的发生是一个相当复杂的过程,促卵泡成熟激素及其受体在卵巢癌发病中的作用机制还不清楚.     

白背飞虱灯下虫量与气象要素关系的相关分析

研究白背飞虱Sogatellafurcifera(Horvath)灯下虫量与气象要素之间的关系。相关分析表明(1)白背飞虱灯下虫量与平均气温、最高气温、最低气温和相对湿度的最优曲线估计为Logistic曲线,其中与3个温度要素之间的相关达到极显著水平,与相对湿度的相关关系达到显著水平;(2)灯下诱虫量与降水量、日照时数、温雨系数和晴雨系数的最优曲线估计为幂函数曲线,除日照时数达到显著水平外,其余3个要素均达到极显著水平;(3)对白背飞虱灯下虫量变化影响较大的因子依次为温雨系数、降水量、日照时数和晴雨系数,相应的偏相关系数分别为0.3908,-0.3727,-0.2996和-0.2268;(4)虫量与相对湿度、平均气温、最低气温和最高气温的偏相关系数分别为-0.1229,0.1152,-0.0410和-0.0106,不相关概率为20.5%~91.3%,远未达到5%的显著水平;(5)通过分析,建立白背飞虱灯下虫量预报方程,为及时进行白背飞虱大田防治提供依据。     

Understanding relationship between sequence and functional evolution in yeast proteins

The underlying relationship between functional variables and sequence evolutionary rates is often assessed by partial correlation analysis. However, this strategy is impeded by the difficulty of conducting meaningful statistical analysis using noisy biological data. A recent study suggested that the partial correlation analysis is misleading when data is noisy and that the principal component regression analysis is a better tool to analyze biological data. In this paper, we evaluate how these two statistical tools (partial correlation and principal component regression) perform when data are noisy. Contrary to the earlier conclusion, we found that these two tools perform comparably in most cases. Furthermore, when there is more than one ‘true’ independent variable, partial correlation analysis delivers a better representation of the data. Employing both tools may provide a more complete and complementary representation of the real data. In this light, and with new analyses, we suggest that protein length and gene dispensability play significant, independent roles in yeast protein evolution. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.