Simple Test Statistics for a Fixed Number of Matched Samples with Ordinal Outcome Variables

In a preceding paper, we (Nurminen et al. 1981) advocated the use of the sole referent series as the basis of estimating moments in the construction of test statistics for comparative studies. Three simple test statistics, two metric approaches and one procedure based on ranks, incorporating this principle are introduced for small matched samples with ordinal outcome variables. Associated methods for computing an “exact” probability value are derived. The techniques are illustrated by real data from a study in the field of occupational health epidemiology.     

Quantifying Histological Features of Cancer Biospecimens for Biobanking Quality Assurance Using Automated Morphometric Pattern Recognition Image Analysis Algorithms

Biorepository-supported translational research depends on high-quality, well-annotated specimens. Histopathology assessment contributes insight into how representative lesions are for research objectives. Feasibility of documenting histological proportions of tumor and stroma was studied in an effort to enhance information regarding biorepository tissue heterogeneity. Using commercially available software, unique spatial-spectral algorithms were developed for applying automated pattern recognition morphometric image analysis to quantify histologic tumor and nontumor tissue areas in biospecimen tissue sections. Measurements were acquired successfully for 75/75 (100%) lymphomas, 76/77 (98.7%) osteosarcomas, and 60/70 (85.7%) melanomas. The percentage of tissue area occupied by tumor varied among patients and tumor types and was distributed around medians of 94% [interquartile range (IQR)=14%] for lymphomas, 84% for melanomas (IQR=24%), and 39% for osteosarcomas (IQR=44%). Within-patient comparisons from a subset, including multiple individual patient specimens, revealed ≤12% median coefficient of variation (CV) for lymphomas and melanomas. Phenotypic heterogeneity of osteosarcomas resulted in 33% median CV. Uniformly applied, tumor-specific pattern recognition software permits automated tissue-feature quantification. Furthermore, dispersion analyses of area measurements across collections, as well as of multiple specimens from individual patients, support using limited tissue slices to gauge features for some tumor types. Quantitative image analysis automation is anticipated to minimize variability associated with routine biorepository pathologic evaluations and enhance biomarker discovery by helping to guide the selection of study-appropriate specimens.     

遗传多样性的取样策略

合理取样是生物多样性有效保护、利用和研究所面临的最基本问题 ,它在很大程度上受到植物自身的生物学特性、环境条件和取样目的的影响。遗传多样性的取样策略是指对一定地理分布范围内的生物个体取样时 ,使样本具有代表性和包含尽可能多的遗传变异的最佳取样方法 ,包括了取样数目 (一个给定区域的居群数和一个居群的个体数 )以及取样方式。包括“哈迪 温伯格平衡 (Hardy WeinbergEquilibrium)”定律在内的居群遗传学基本原理是研究取样策略的理论基础 ,在此基础上可以对居群内的取样个体数及应获取的居群数进行理论计算 ,同时还可以根据物种居群的遗传结构特点和环境条件的异质性来决定取样的方式。因此 ,应该依据研究对象本身的特点和取样的目的来确定某一特定区域的居群取样数 ,以及某一居群内的样本数及取样方式。     

桔小实蝇分子生物学研究中样品采集及保存处理的改进方法

介绍了一种果实蝇,桔小实蝇Bactroceradorsalis的虫样采集和保存处理的方法。利用一种简易的诱捕装置对于野外短时间、大面积采集实蝇虫样效果显著;同时,用TE溶液浸泡的干燥虫样适用于桔小实蝇的DNA抽提和PCR扩增。这种虫样采集和保存方法也适用于果实蝇属其它几类实蝇的分子生物学研究。     

An Application of Logistic Models to the Analysis of Ordinal Responses

Logistic probability models—models linear in the log odds of the outcome event—have found extensive application in modelling of unordered categorical responses. This paper illustrates some extensions of logistic models to the modelling of probabilities of ordinal responses. The extensions arise naturally from discrete probability models for the conditional distribution of the ordinal response, as well as from linear modelling of the log odds of response. Methods of estimation and examination of fit developed for the binary logistic model extend in a straightforward manner to the ordinal models. The models and methods are illustrated in an analysis of the dependence of chronic obstructive respiratory disease prevalence on smoking and age.     

Goodness-of-Fit Tests for the Logistic Regression Model for Matched Case-Control Studies

A number of statistics have recently been proposed to asssess the fit of the multiple logistic regression model in both prospective and retrospective studies involving two independent samples as well as in cross sectional studies. These statistics are not appropriate for assessing fit with matched case-control studies. This paper presents methods for assessing fit for matched case-control studies. Both parametric and nonparametric approaches are suggested even though none are directly analogous to the statistics proposed in the unmatched situation. Several examples are included to illustrate the methods.     

WHAT SHOULD RESEARCH PARTICIPANTS UNDERSTAND TO UNDERSTAND THEY ARE PARTICIPANTS IN RESEARCH?

To give valid informed consent to participate in clinical research, potential participants should understand the risks, potential benefits, procedures, and alternatives. Potential participants also should understand that they are being invited to participate in research. Yet it is unclear what potential participants need to understand to satisfy this particular requirement. As a result, it is unclear what additional information investigators should disclose about the research; and it is also unclear when failures of understanding in this respect undermine the validity of potential participants' informed consent. An analysis of individuals' interests suggests that potential participants need to understand three additional facts to understand that they are being invited to participate in research: 1) research contribution : those who enroll in the study will be contributing to a project designed to gather generalizable knowledge to benefit others in the future; 2) research relationship : the investigators will rely on participants' efforts to gather the generalizable knowledge to benefit others; and 3) research impact : the extent to which participating in the study will alter what participants do and what happens to them.     

Searching for DNA in museum specimens: a comparison of sources in a mammal species

The number of genetic studies that use preserved specimens as sources of DNA has been steadily increasing during the last few years. Therefore, selecting the sources that are more likely to provide a suitable amount of DNA of enough quality to be amplified and at the minimum cost to the original specimen is an important step for future research. We have compared different types of tissue (hides vs. bones) from museum specimens of Iberian lynx and multiple alternative sources within each type (skin, footpad, footpad powder, claw, diaphysis, maxilloturbinal bone, mastoid process and canine) for DNA yield and probability of amplification of both mitochondrial and nuclear targets. Our results show that bone samples yield more and better DNA than hides, particularly from sources from skull, such as mastoid process and canines. However, claws offer an amplification success as high as bone sources, which makes them the preferred DNA source when no skeletal pieces have been preserved. Most importantly, these recommended sources can be sampled incurring minimal damage to the specimens while amplifying at a high success rate for both mitochondrial and microsatellite markers.     

FINES,ORDERS, FEAR . . . AND CONSENT? MEDICAL RESEARCH IN EAST AFRICA,C. 1950s

This article reconstructs the history of medical research in East Africa (Kenya, Tanganyika, Uganda), laying out the lies, rumours, and oppressive techniques that made research such a fraught enterprise during the colonial era. The focus is on the beginning stages of medical research: researchers' arrivals, villagers' responses, the gathering of subjects and consent. New archival and oral sources gathered in East Africa illuminate the research encounter and reintegrate the perspective of villagers cum subjects. Data from the 1950s shows that upon arrival in a village, researchers regularly lied in order to avoid sensitive topics and sidestep potential opposition. Misinformation fuelled villagers' fears, skepticism and rumours of blood stealing researchers. When it came to gathering subjects, researchers were rarely involved in the challenging work of enticing villagers to participate, preferring to rely on chiefs. Chiefs, however, often relied on heavy-handed and ethically questionable techniques. The article concludes by looking at the much-discussed concept of group consent, and showing that historically a chief never had the authority to consent on behalf of villagers.     

Biomedical applications of photon-induced X-ray fluorescence

An X-ray fluorescence method for in vitro analysis of trace elements is presented. The method is characterized by the use of an X-ray tube with secondary targets as a quasimonoenergetic radiation source, and by “infinitely thin” specimens. Different aspects have been examined in order to optimize the sensitivity of the method. It is extremely important to use secondary targets as pure as possible and collimators internally covered by the same element as the secondary target. It is also important to reduce the contribution at the XRF spectrum of photons scattered by the sample, by the sample support, and by the air. Preconcentration techniques can conveniently also be used to this purpose. In this work, biological samples are preconcentrated by reducing them to ash. Typical sensitivities obtained are in the order of 1–5 ng/cm² in a counting time of 10³ s for elements with atomic number ranging from 24 (chromium) to 40 (zirconium).     

生物样本库及其伦理问题简介

随着分子和基因组信息对流行病学影响的增加,无数遗传流行病学研究和后人类基因组计划的研究都越来越依赖人类生物样本库的使用。生物样本库的范围也已横跨学术或者医院环境下的小数量收集到大规模的全国性储藏。尽管生物样本库的概念并不新,但是在基因组研究和后人类基因组计划的背景下,伴随它们十几年极大发展的是无数待解决的伦理挑战。从生物样本库的概念着手,介绍了其与一般遗传数据库的区别以及建立生物样本库的意义;然后介绍并比较国际上已有的生物样本库,以及其伦理问题和伦理法律框架的发展趋势。