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91.
For designs with longitudinal observations of ordered categorical data, a nonparametric model is considered where treatment effects and interactions are defined by means of the marginal distributions. These treatment effects are estimated consistently by ranking methods. The hypotheses in this nonparametric setup are formulated by means of the distribution functions. The asymptotic distribution of the estimators for the nonparametric effects are given under the hypotheses. For small samples, a rather accurate approximation is suggested. A clinical trial with ordered categorical data is used to motivate the ideas and to explain the procedures which are extensions of the Wilcoxon‐Mann‐Whitney test to factorial designs with longitudinal observations. The application of the procedures requires only some trivial regularity assumptions.  相似文献   
92.
Drought is a major and constantly increasing abiotic stress factor, thus limiting chickpea production. Like other crops, Kabuli Chickpea genotypes are screened for drought stress through Multi-environment trials (METs). Although, METs analysis is generally executed taking into account only one trait, which provides less significant reliability for the recommendation of genotypes as compared to multi trait-based analysis. Multi trait-based analysis could be used to recommend genotypes across diverse environments. Hence, current research was conducted for selection of superior genotypes through multi-trait stability index (MTSI) by using mixed and fixed effect models under six diverse environments. The genotypic stability was computed for all traits individually using the weighted average of absolute scores from the singular value decomposition of the matrix of best linear unbiased predictions for the genotype vs environment interaction (GEI) effects produced by a linear mixed-effect model index. A superiority index, WAASBY was measured to reflect the MPS (Mean performance and stability). The selection differential for the WAASBY index was 11.2%, 18.49% and 23.30% for grain yield (GY), primary branches per plant (PBP) and Stomatal Conductance (STOMA) respectively. Positive selection differential (0.80% ≤ selection differential ≤ 13.00%) were examined for traits averaged desired to be increased and negative (-0.57% ≤ selection differential ≤ -0.23%) for those traits desired to be reduced. The MTSI may be valuable to the plant breeders for the selection of genotypes based on many characters as being strong and simple selection process. Analysis of MTSI for multiple environments revealed that, the genotypes G20, G86, G31, G28, G116, G12, G105, G45, G50, G10, G30, G117, G81, G48, G85, G17, G32, G4, and G37 were the most stable and high yielding out of 120 chickpea genotypes, probably due to high MPS of selected traits under various environments. It is concluded that identified traits can be utilized as genitors in hybridization programs for the development of drought tolerant Kabuli Chickpea breeding material.  相似文献   
93.
Longini , Datta , and Halloran (1996) proposed to design HIV vaccine trials in a way that will permit the simultaneous estimation of the vaccine effects on susceptibility to infection and on infectiousness of vaccine brak-throughs. The main feature of their design is the inclusion of steady partners of trial participants. They estimate four parameters from the vaccine trial: the probability that a susceptible person will become infected from his/her steady partner, the probability of becoming infected from outside the partnership, the vaccine efficacy for susceptibility and the vaccine efficacy for infectiousness. We show how the estimates of these parameters can be used to predict the attack rate in a given population during a specified period following mass-vaccination. This is an iterative method, as the attack rate depends on the HIV prevalence which, in turn, depends on the number of new cases during that period. The same method is also used to estimate the attack rate in that population during the same period in the absence of vaccination. The estimated attack rates allow us to estimate the population vaccination effectiveness, defined as the fraction HIV cases prevented by a vaccination program.  相似文献   
94.
The classical group sequential test procedures that were proposed by Pocock (1977) and O'Brien and Fleming (1979) rest on the assumption of equal sample sizes between the interim analyses. Regarding this it is well known that for most situations there is not a great amount of additional Type I error if monitoring is performed for unequal sample sizes between the stages. In some cases, however, problems can arise resulting in an unacceptable liberal behavior of the test procedure. In this article worst case scenarios in sample size imbalancements between the inspection times are considered. Exact critical values for the Pocock and the O'Brien and Fleming group sequential designs are derived for arbitrary and for varying but bounded sample sizes. The approach represents a reasonable alternative to the flexible method that is based on the Type I error rate spending function. The SAS syntax for performing the calculations is provided. Using these procedures, the inspection times or the sample sizes in the consecutive stages need to be chosen independently of the data observed so far.  相似文献   
95.
96.
More than fifteen years ago, it was noted that the failure rate of antidepressant clinical trials was high, and such negative outcomes were thought to be related to the increasing magnitude of placebo response. However, there is considerable debate regarding this phenomenon and its relationship to outcomes in more recent antidepressant clinical trials. To investigate this, we accessed the US Food and Drug Administration (FDA) reviews for sixteen antidepressants (85 trials, 115 trial arms, 23,109 patients) approved between 1987 and 2013. We calculated the magnitude of placebo and antidepressant responses, antidepressant‐placebo differences, as well as the effect sizes and success rates, and compared these measures over time. Exploratory analysis investigated potential changes in trial design and conduct over time. As expected, the magnitude of placebo response has steadily grown in the past 30 years, increasing since 2000 by 6.4% (r=0.46, p<0.001). Contrary to expectations, a similar increase has occurred in the magnitude of antidepressant response (6.0%, r=0.37, p<0.001). Thus, the effect sizes (0.30 vs. 0.29, p=0.42) and the magnitude of antidepressant‐placebo differences (10.5% vs. 10.3%, p=0.37) have remained statistically equivalent. Furthermore, the frequency of positive trial arms has gone up in the past 15 years (from 47.8% to 63.8%), but this difference in frequency has not reached statistical significance. Trial design features that were previously associated with a possible lower magnitude of placebo response were not implemented, and their relationship to the magnitude of placebo response could not be replicated. Of the 34 recent trials, two implemented enhanced interview techniques, but both of them were unsuccessful. The results of this study suggest that the relationship between the magnitude of placebo response and the outcome of antidepressant clinical trials is weak at best. These data further indicate that antidepressant‐placebo differences are about the same for all of the sixteen antidepressants approved by the FDA in the past thirty years.  相似文献   
97.
Adipose-derived stem cells (ASCs) are mesenchymal stem cells (MSCs) that are obtained from abundant adipose tissue, adherent on plastic culture flasks, can be expanded in vitro, and have the capacity to differentiate into multiple cell lineages. Unlike bone marrow-derived MSCs, ASCs can be obtained from abundant adipose tissue by a minimally invasive procedure, which results in a high number of cells. Therefore, ASCs are promising for regenerating tissues and organs damaged by injury and diseases. This article reviews the implications of ASCs in tissue regeneration.  相似文献   
98.
There is an alleged tension between undue inducement and exploitation in research trials. This paper considers claims that increasing the benefits to research subjects enrolled in international, externally‐sponsored clinical trials should be avoided on the grounds that it may result in the undue inducement of research subjects. It proceeds from the premise that there are good grounds for thinking that, at least some, international research sponsors exploit trial participants because they do not provide the research population with a fair share of the benefits of research. This provides a prima facie argument for increasing the benefits for research participants. Concern over undue inducement is a legitimate moral concern; however, if this concern is to prevent research populations from receiving their fair share of benefits from research there must be sufficient evidence that these benefits will unduly influence patients’ decision‐making regarding trial participation. This article contributes to the debate about exploitation versus undue inducement by introducing an analysis of the available empirical research into research participants’ motivations and the influence of payments on research subjects’ behaviour and risk assessment. Admittedly, the available research in this field is limited, but the research that has been conducted suggests that financial rewards do not distort research subjects’ behaviour or blind them to the risks involved with research. Therefore, I conclude that research sponsors should prioritise the prevention of exploitation in international research by providing greater benefits to research participants.  相似文献   
99.
Both cucumber mosaic virus (CMV) and tobacco mosaic virus (TMV) coat protein (CP) genes have been transferred to chilli pepper (Capsicum annuum var. Longunt) cultivar 8212 by a modified procedure of Agrobacterium tumefaciens-mediated transformation using hypocotyl as the explant. PCR analysis revealed the presence of both CMV and TMV CP genes in at least 11 primary transformants out of 49 kanamycin-resistant chili pepper plants. Ten T1 lines from five independent transformation events were identified as putative homozygous transgenic lines based on the rooting assay of their T2 seedlings on the kanamycin-containing media. Integration and expression of CMV CP and TMV CP transgenes in one of the homozygous line, 16-13, were confirmed bySouthern blot, RT-PCR and western blot analyses. Line 16-13 was highly resistant to infection of homologous CMV and TMV strains in greenhouse conditions when successively challenged with CMV and TMV or challenged with TMV alone.Futhermore, field trials on T2, T3 and T4 progenies of Line 16-13 were performed on scales of 123, 300 and 10,000 plants, respectively, in consecutive years 1996, 1997 and 1998 with the permission of the Chinese government authority. The transgenic plants displayed delayed symptom development and significantly milder disease severity in field conditions when compared to untransformed chili pepper plants, resulting in 47 and 110% increase in pepper fruit yield in surveys conducted in 1997 and 1998 trials, respectively. Finally, quality analysis and biosafety assesment were performed on transgenic chili pepper fruit concurrently with the control fruit, and demonstrated that the transgenic chili pepper fruit is substantially equivalent to the non-transgenic pepper in terms of the quality and biosafety when consumed as a food additive.  相似文献   
100.
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