The significance threshold for coherence when using the Welch's periodogram method: Effect of overlapping segments

A classical tool to identify coupling mechanisms between two biological signals is transfer function (TF) analysis, commonly estimated by the Welch's periodogram method. However, the reliability of TF estimation depends on the coherence function, an index of linear coupling in the frequency domain. Thus, a threshold value has to be determined before assuming a coupling between two signals at a given frequency.Koopmans (The spectral analysis of time series) proposed a theoretical expression in the case of non-overlapping segments. Overlapping segments, however, improves the estimation of TF.In the present study, a modification of the expression by Koopmans is proposed for taking into account the effect of the overlapping procedure, including the most common case of a 50% overlapping ratio. Simulation tests were done on non-coherent signals (using the Hanning window), and a Kolmogorov–Smirnov test was used to check for the adequacy with the proposed threshold formula. The results showed that for an overlapping ratio of 50%, no statistical difference could be found (P > 0.05), except when using less than seven segments.The method has been applied to the computation of the transfer function between systolic blood pressure and heart rate.     

Adjusting O'Brien's test to control type I error for the generalized nonparametric Behrens-Fisher problem

O'Brien (1984, Biometrics 40, 1079-1087) introduced a simple nonparametric test procedure for testing whether multiple outcomes in one treatment group have consistently larger values than outcomes in the other treatment group. We first explore the theoretical properties of O'Brien's test. We then extend it to the general nonparametric Behrens-Fisher hypothesis problem when no assumption is made regarding the shape of the distributions. We provide conditions when O'Brien's test controls its error probability asymptotically and when it fails. We also provide adjusted tests when the conditions do not hold. Throughout this article, we do not assume that all outcomes are continuous. Simulations are performed to compare the adjusted tests to O'Brien's test. The difference is also illustrated using data from a Parkinson's disease clinical trial.     

On the finite sample distribution of the likelihood ratio statistic for testing heterogeneity in meta-analysis

In meta-analysis, hypothesis testing is one of the commonly used approaches for assessing whether heterogeneity exists in effects between studies. The literature concluded that the Q-statistic is clearly the best choice and criticized the performance of the likelihood ratio test in terms of the type I error control and power. However, all the criticism for the likelihood ratio test is based on the use of a mixture of two chi-square distributions with 0 and 1 degrees of freedom, which is justified only asymptotically. In this study, we develop a novel method to derive the finite sample distribution of the likelihood ratio test and restricted likelihood ratio test statistics for testing the zero variance component in the random effects model for meta-analysis. We also extend this result to the heterogeneity test when metaregression is applied. A numerical study shows that the proposed statistics have superior performance to the Q-statistic, especially when the number of studies collected for meta-analysis is small to moderate.     

血源乙型肝炎疫苗的效力稳定性试验研究

对保存温度分别为３７℃、２－８℃、１８－２２℃,保存时间分别为１年、１．５年、２．５年的血源乙型肝炎疫苗进行了效力稳定性试验。结果表明,３７℃保存４周经效力测试已无活性存在,而２－８℃、１８－２２℃保存１年、１．５年、２．５年的疫苗经效力试验测定,２－８℃试ＥＤ５０／参ＥＤ５０比值可达１．０５－２．７４,２．５年后比值仍可达１．０５－１．６７,保持在合格限以上。但１８－２２℃试ＥＤ５０／参ＥＤ５０比值为０．７８－１．５２,其活性已下降。试验结果表明血源乙型肝炎疫苗在２－８℃保存的疫苗稳定性良好,其有效期至少在２．５年以上。     

The variance for the disequilibrium coefficient in the individual Hardy-Weinberg test

It is of interest to detect the deviation from Hardy-Weinberg proportion (HWP) for a particular heterozygote. Hernández and Weir (1989, Biometrics 45, 53-70) suggested a disequilibrium coefficient approach and proposed a 1-d.f. chi2 test. This note derives the appropriate variance under the null hypothesis for performing this individual HWP test. Examples of applying the test to human genetic disease data are presented.     

重组乙型肝炎疫苗(CHO细胞)鉴别试验的方法研究

目的：建立重组乙型肝炎疫苗(CHO细胞)鉴别试验的方法。方法：取重组乙型肝炎疫苗(CHO细胞)以1：10比例加入lmol/L盐酸调节pH值,采用ELISA双抗体夹心法检测,同时设以氢氧化铝、未处理的重组乙型肝炎疫苗、狂犬疫苗、出血热疫苗,以及试剂盒的阴、阳性作为对照。结果：狂犬疫苗、出血热疫苗及氢氧化铝对照为阴性,直接检测重组乙型肝炎疫苗(CHO细胞)呈弱阳性,加入盐酸调节pH值后原倍样品呈弱阳性,10倍稀释后呈强阳性。采用该方法检测5批疫苗均呈强阳性。组内平行试验,组间重复试验。结论：将重组乙型肝炎疫苗(CHO细胞)调节pH值后10倍稀释,用ELISA双抗体夹心法检测呈阳性,而且稳定可靠,该方法可用于该疫苗的鉴别试验。     

Development of a validation protocol to determine the ability of screw-top containers to be watertight and to withstand impact damage from accidental dropping

Polypropylene screw-top containers are used to collect, transport and store a variety of tissues within tissue banks. These containers are validated for use by tissue banks but no standard validation protocol is used. We present here a protocol for testing screw-top containers for leakage, evaporation and the ability to withstand accidental impact damage. Three different containers were tested, MedFor S072, MedFor S277 and MacoPharma PROT0483. The validation can detect differences between different manufacturer’s containers and this protocol will be used in future validations of screw-top containers within National Blood Service Tissue Services.     

Properties and Application of the Location-Test V (n,k)

The present paper is concerned with the properties of a test statistic V(n, k) to test location differences in the one-sample case with known hypothetical distribution G(x). The test is similar to the WILCOXON two-sample statistic after replacement of the second sample by quantiles of the hypothetical distribution. A comparison with the exact distribution of V(n, k) shows that an approximation by means of the normal distribution provides good results even for small sample sizes. The V-test is unbiased against one-tailed alternatives and it is consistent with a restriction which is hardly relevant in practical applications. With regard to the application we are interested especially in the power and robustness against extreme observations for small sample size n. It is shown that in a normal distribution with known standard deviation V(n, k) is more powerful than STUDENT's t for small n and more robust in the sense considered here. The test statistic is based on grouping of the observations into classes of equal expected frequency. A generalization to arbitrary classes provides an essential extension of applicability such as to discrete distributions and to situations where only relative frequencies of G(x) in fixed classes are known.     

The Power of the Mantel-Haenszel Test when Adjustment is by the True or Estimated Propensity Score

The power of the Mantel-Haenszel test for no treatment effect in the case of binary exposure and response variates was examined through simulation studies when subclasses were formed on the basis of the true and estimated propensity scores and by direct stratification on two continuous covariates. The power of these tests was also compared to the score test in a misspecified logistic regression model. In general adjustment by the true propensity score was most likely to reject a false null hypothesis, the score test was more likely to reject a false null hypothesis than the Mantel-Haenszel test when adjustment is by the estimated propensity score or subclassification on the covariates. There was litte difference in the observed powers of the Mantel-Haenszel tests between adjustment by the estimated propensity score and subclassification on the covariates.     

Smooth tests for the zero-inflated poisson distribution

In this article we construct three smooth goodness-of-fit tests for testing for the zero-inflated Poisson (ZIP) distribution against general smooth alternatives in the sense of Neyman. We apply our tests to a data set previously claimed to be ZIP distributed, and show that the ZIP is not a good model to describe the data. At rejection of the null hypothesis of ZIP, the individual components of the test statistic, which are directly related to interpretable parameters in a smooth model, may be used to gain insight into an alternative distribution.     

嗜酸乳杆菌LA-G80的毒理学研究

目的对嗜酸乳杆菌的毒性进行研究。方法采用大、小鼠急性毒性试验、Ames试验、小鼠骨髓细胞微核试验、小鼠精子畸形试验和大鼠30 d喂养等对嗜酸乳杆菌进行安全性试验研究。结果急性经口毒性试验表明,大、小鼠灌胃给予嗜酸乳杆菌,最大耐受剂量雌雄两性别均大于20.0 g/kg体重,Ames试验、微核试验和精子畸形试验结果均为阴性。大鼠30 d喂养试验结果表明各项指标均未见明显毒性反应。结论在本次实验条件下,嗜酸乳杆菌未见遗传毒性。由此可初步判定,使用嗜酸乳杆菌是安全可靠的。     

吸附精制百日咳菌苗、白喉、破伤风类毒素混合制剂稳定性的研究

将连续生产并已申报人体接种反应观察的三批吸附精制百日咳菌苗、白喉、破伤风类毒素混合制剂,分别于４～８℃、１８～２２℃、３７℃贮存半年、１年、１年半和３０天,然后以小鼠法或豚鼠法对该制剂进行安全稳定性、效力稳定性以及毒性逆转等测试。其毒力安全稳定性试验表明,三批混合制剂中的精制百日咳菌苗在４～８℃贮半年、１年、１年半后、它们的ＢＷＤＵ／ｍｌ、ＬＰＵ／ｍｌ、ＨＳＵ／ｍｌ均无显著性差异（Ｐ＞０．０５）;白喉及破伤风类毒素在４～８℃贮存半年,１年、１年半以及１８～２２℃贮存半年和３７℃贮存３０天后,三批测试组的豚鼠均健存且体重增加。在效力稳定性试验中,４～８℃贮存１年和１年半后精制百日咳菌苗的效力与贮存前（分别为２６．７３ＩＵ／ｍｌ、２１．０２ＩＵ／ｍｌ、１９．１７ＩＵ／ｍｌ）无显著性差异（ｔ＝０．１１４;Ｐ＞０．０５）;白喉及破伤风类毒素４～８℃贮存长达１年半后,效力仍在２～３．２ＩＵ／ｍｌ,动物保护率仍可达８０～１００％。三批混合制剂在３７℃贮存３０天后,通过Ｓｃｈｉｃｋ毒性试验及测定ＢＷＤＵ／ｍｌ、ＬＰＵ／ｍｌ、ＨＳＵ／ｍｌ各指标显示,精制百日咳菌苗、白喉和破伤风类毒素无毒性逆转。说明该吸附精制百、白、破混合