A Bootstrap Procedure for Adaptive Selection of the Test Statistic in Flexible Two‐Stage Designs

Adaptive two‐stage designs allow a data‐driven change of design characteristics during the ongoing trial. One of the available options is an adaptive choice of the test statistic for the second stage of the trial based on the results of the interim analysis. Since there is often only a vague knowledge of the distribution shape of the primary endpoint in the planning phase of a study, a change of the test statistic may then be considered if the data indicate that the assumptions underlying the initial choice of the test are not correct. Collings and Hamilton proposed a bootstrap method for the estimation of the power of the two‐sample Wilcoxon test for shift alternatives. We use this approach for the selection of the test statistic. By means of a simulation study, we show that the gain in terms of power may be considerable when the initial assumption about the underlying distribution was wrong, whereas the loss is relatively small when in the first instance the optimal test statistic was chosen. The results also hold true for comparison with a one‐stage design. Application of the method is illustrated by a clinical trial example.     

INVO: a simple, low cost effective assisted reproductive technology

⁵Correspondence address. E-mail: clauderanoux{at}bioxcell.com INVO procedure is a simple and effective infertility treatmentthat uses a new device, the INVOcell. INVO can be performedin a physician's office or in a satellite facility of an IVFcenter. The INVO procedure consists of fertilization of oocyte(s)and early embryo development in the INVOcell placed into thematernal vaginal cavity for incubation. The vaginal cavity replacesthe complex in vitro fertilization (IVF) laboratory. This studypresents the specially designed device, INVOcell that has receivedCE Certification. INVOcell overcomes the disadvantages of thepreviously used prototype and makes the procedure simpler andreproducible. INVO is a proven procedure that has demonstratedcomparable results to conventional IVF when comparative studieswere performed. Over 800 cycles have been published worldwidethat showed a clinical pregnancy rate of 19.6%. The INVO technologycan be performed in an office setting with minor capital equipment.INVO is a simple low-cost procedure that can be available almosteverywhere. INVO allows the treatment of a new population ofinfertile couples who could not benefit from IVF due to costand availability. The participation of the patient in the processof fertilization and early embryo development is a psychologicalbenefit that creates a high level of acceptance of INVO.     

Assessment of the eutrophication status of transitional,coastal and marine waters within OSPAR

Eutrophication (nutrient enrichment and subsequent processes) and its adverse ecosystem effects have been discussed as main issues over the last 20 years in international conferences and conventions for the protection of the marine environment such as the North Sea Conferences and the 1992 OSPAR Convention (OSPAR; which combined and updated the 1972 Oslo Convention on dumping waste at the sea and the 1974 Paris Convention on land-based sources of marine pollution). OSPAR committed itself to reduce phosphorus and nitrogen inputs (in the order of 50% compared with 1985) into the marine areas and ‘to combat eutrophication to achieve, by the year 2010, a healthy marine environment where eutrophication does not occur’. Within OSPAR, the Comprehensive Procedure (COMPP) has been developed and used to assess the eutrophication status of the OSPAR maritime area in an harmonised way. This is based on classification in terms of the following types of areas Non-Problem Areas (no effects), Potential Problem Areas (not enough data to assess effects) and Problem Areas (effects due to elevated nutrients and/or due to transboundary transport from adjacent areas). The COMPP consists of a set of harmonised assessment criteria with their area-specific assessment levels and an integrated area classification approach. The criteria cover all aspects of nutrient enrichment (nutrient inputs, concentrations and ratios) as well as possible direct effects (e.g. increased levels of nuisance and/or toxic phytoplankton species, shifts and/or losses of submerged aquatic vegetation) and indirect effects (e.g. oxygen deficiency, changes and/or death of benthos, death of fish, algal toxins). The COMPP also includes supporting environmental factors. It takes account of synergies and harmonisation with the EC Water Framework Directive, and has formed a major basis for the EC eutrophication guidance. Recently, additional components, such as total nitrogen, total phosphorus and transboundary transports have been included in the assessment of, e.g. the German Bight. The second application of the COMPP resulting in an update of the eutrophication status of the OSPAR maritime area will be finalised in 2008, and will include the agreed integrated set of Ecological Quality Objectives (EcoQOs) with respect to eutrophication. Guest editors: J. H. Andersen & D. J. Conley Eutrophication in Coastal Ecosystems: Selected papers from the Second International Symposium on Research and Management of Eutrophication in Coastal Ecosystems, 20–23 June 2006, Nyborg, Denmark     

A comparison of responses and stimuli as time markers

A rat's behavior, as well as a stimulus, may be a time marker. But do they lead to similar performance? Eight rats were trained on a 20-s DRL procedure in which head-entry responses were time markers, i.e., each head-entry response indicated that food would not be delivered for 20 s. Concurrently, eight rats were trained on a control procedure in which light stimuli, yoked to the responses of a rat in the DRL procedure, were time markers, i.e., each light stimulus indicated that food would not be delivered for 20 s. A comparison of performance between the two groups showed a lower response rate in the DRL procedure than in the yoked control procedure. However, similar response patterns between the two groups were observed, suggesting that rats anticipated the food similarly with a stimulus or a response as the time marker.     

Fewer peak trials per session facilitate acquisition of peak responding despite elimination of response rate differences

It has been shown in previous research [Kaiser, D.H., 2008. The proportion of fixed interval trials to probe trials affects acquisition of the peak procedure fixed interval timing task. Behav. Process., 77 (1), 100-108] that rats acquired peak responding sooner when fewer peak trials were presented during sessions of training with the peak procedure timing task. One potential problem with that research was that there were large differences in response rates among the groups. The present experiment attempted to examine the effect of proportion of peak trials when differences in response rate were controlled. Two groups of rats were each simultaneously tested with two versions of the peak procedure. One group was tested with 10% peak trials per session, and the other group was tested with 50% peak trials per session. For both of the groups, one of the panel lights and levers was associated with the traditional peak procedure. The other panel light and lever was associated with a similar peak procedure; however, reinforcement was provided at the end of each peak trial. This manipulation eliminated differences in response rate among the groups, however, Group 10% acquired peak responding more quickly than Group 50%, effectively replicating previous work in the absence of a response bias.     

Spatial distribution of benthic algae in the Gangqu River,Shangrila, China

This study consisted of sampling benthic algae at 32 sites in the Gangqu River, an important upstream tributary of the Yangtze River. Our aims were to characterize the benthic algae communities and relationships with environmental variables. Among the 162 taxa observed, Achnanthes linearis and Achnanthes lanceolata var. elliptica were the dominant species (17.10% and 14.30% of the total relative abundance, respectively). Major gradients and principal patterns of variation within the environmental variables were detected by principal component analysis (PCA). Then non-metric multidimensional scaling (NMS) divided all the sites into three groups, which were validated by multi-response permutation procedures (MRPP). Canonical correspondence analysis (CCA) indicated that three environmental variables (TN, TDS, and TP) significantly affected the distribution of benthic algae. Weighted averaging regression and cross-calibration produced strong models for predicting TN and TDS concentration, which enabled selection of algae taxa as potentially sensitive indicators of certain TN and TDS levels: for TN, Achnanthes lanceolata, Achnanthes lanceolata var. elliptica, and Cymbella ventricosa var. semicircularis; for TDS, Cocconeis placentula, Cymbella alpina var. minuta, and Fragilaria virescens. The present study represents an early step in establishing baseline conditions. Further monitoring is suggested to gain a better understanding of this region.     

Electroeluting DNA Fragments

Purified DNA fragments are used for different purposes in Molecular Biology and they can be prepared by several procedures. Most of them require a previous electrophoresis of the DNA fragments in order to separate the band of interest. Then, this band is excised out from an agarose or acrylamide gel and purified by using either: binding and elution from glass or silica particles, DEAE-cellulose membranes, "crush and soak method", electroelution or very often expensive commercial purification kits. Thus, selecting a method will depend mostly of what is available in the laboratory. The electroelution procedure allows one to purify very clean DNA to be used in a large number of applications (sequencing, radiolabeling, enzymatic restriction, enzymatic modification, cloning etc). This procedure consists in placing DNA band-containing agarose or acrylamide slices into sample wells of the electroeluter, then applying current will make the DNA fragment to leave the agarose and thus be trapped in a cushion salt to be recovered later by ethanol precipitation.     

系统发育分析中的最大简约法及其优化

随着生物技术的不断发展和系统发育学的深入研究, 在重构系统发育树时, 研究人员往往要面对更多的挑战和困难, 比如： (1)需要分析的样本数（物种数或个体数）不断增加; (2)需要分析的数据量迅速扩大。尤其在基因组测序技术的推动下, 基于分子信息的系统发育重建需要极大的计算量, 因此数学方法、 计算机技术以及其他辅助工具对于系统发育重建的效率和精确度起着至关重要的作用。最大简约法（maximum parsimony）是一种重要的系统发育重建方法, 提高其计算效率对系统发育学研究具有重要意义, 针对该算法的优化改进需要生物学家和计算机专家的共同努力。本文通过详细地阐述最大简约法的计算流程, 分析其参数选择对计算效率的影响, 帮助更多的计算机使用者, 在并不了解系统发育学基础的情况下, 更方便地针对实际的系统发育算法问题给出更好、 更快、 更精准的解决方案; 同时为系统发育研究工作者, 较为清晰地解释最大简约法的构树思想和计算逻辑, 推动针对最大简约法的不断改进与优化。     

Optimal sampling in retrospective logistic regression via two-stage method

Case-control sampling is popular in epidemiological research because of its cost and time saving. In a logistic regression model, with limited knowledge on the covariance matrix of the point estimator of the regression coefficients a priori, there exists no fixed sample size analysis. In this study, we propose a two-stage sequential analysis, in which the optimal sample fraction and the required sample size to achieve a predetermined volume of a joint confidence set are estimated in an interim analysis. Additionally required observations are collected in the second stage according to the estimated optimal sample fraction. At the end of the experiment, data from these two stages are combined and analyzed for statistical inference. Simulation studies are conducted to justify the proposed two-stage procedure and an example is presented for illustration. It is found that the proposed two-stage procedure performs adequately in the sense that the resultant joint confidence set has a well-controlled volume and achieves the required coverage probability. Furthermore, the optimal sample fractions among all the selected scenarios are close to one. Hence, the proposed procedure can be simplified by always considering a balance design.     

91例主动脉夹层动脉瘤的临床治疗体会

目的:依据临床经验,熟练运用开放手术、腔内修复术及杂交手术方法治疗各类主动脉夹层动脉瘤。方法:收集2009年7月~2013年1月在我院手术治疗的主动脉夹层动脉瘤患者共91例,StanfordB型夹层动脉瘤36例(其中21例降主动脉瘤、9例腹主动脉及双髂动脉瘤行腔内覆膜支架隔绝术,6例行腹主动脉人工血管置换术),StanfordA型夹层动脉瘤55例(其中单纯Sun,s手术12例伴Bentall术6例,Bentall术伴部分主动脉弓人工血管置换36例,1例行Ⅱ型的主干与分支动脉人工血管转流+介入腔内隔绝降主动脉及左半弓杂交术),分别以不同的手术方法给予治疗。结果:顺利治愈出院85例,死亡6例,4例因全弓置换术后出现难以控制的大出血、肠坏死、肾功能不全、少尿等并发症而死亡,2例死于Bentall术后严重多功能脏器急性衰竭,1例杂交手术术后出现高血压伴神经系统并发症,1例伴肺部感染及低心排综合征,给予对症治疗后效果不佳,有2例出现肾功能不全,经过透析治愈。腔内修复术后有神经系统的并发症2例,下肢的功能障碍2例,少量内漏4例,以上并发症均经对症治疗后痊愈。术后随访76例,时间3~12个月,除2例于术后第9个月死亡、1例因脑梗塞、脑血管意外等与手术无关的疾病而死亡,2例因吻合口动脉瘤或动脉瘤破裂大出血死亡外,余患者生活状态良好,心功能在I~Ⅱ级。结论:根据主动脉瘤疾病的临床特点和定位诊断,合理选择和运用治疗方法使手术操作变得更为迅速、安全和方便,同时能够取得良好的临床治疗效果。