共查询到20条相似文献，搜索用时 15 毫秒
1.
Guoqing Diao Guanghan F. Liu Donglin Zeng William Wang Xianming Tan Joseph F. Heyse Joseph G. Ibrahim 《Biometrics》2019,75(3):1000-1008
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Maximilian Beckers Colin M. Palmer Carsten Sachse 《Acta Crystallographica. Section D, Structural Biology》2020,76(4):332-339
Confidence maps provide complementary information for interpreting cryo‐EM densities as they indicate statistical significance with respect to background noise. They can be thresholded by specifying the expected false‐discovery rate (FDR), and the displayed volume shows the parts of the map that have the corresponding level of significance. Here, the basic statistical concepts of confidence maps are reviewed and practical guidance is provided for their interpretation and usage inside the CCP‐EM suite. Limitations of the approach are discussed and extensions towards other error criteria such as the family‐wise error rate are presented. The observed map features can be rendered at a common isosurface threshold, which is particularly beneficial for the interpretation of weak and noisy densities. In the current article, a practical guide is provided to the recommended usage of confidence maps. 相似文献
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The paper is concerned with expected type I errors of some stepwise multiple test procedures based on independent p‐values controlling the so‐called false discovery rate (FDR). We derive an asymptotic result for the supremum of the expected type I error rate(EER) when the number of hypotheses tends to infinity. Among others, it will be shown that when the original Benjamini‐Hochberg step‐up procedure controls the FDR at level α, its EER may approach a value being slightly larger than α/4 when the number of hypotheses increases. Moreover, we derive some least favourable parameter configuration results, some bounds for the FDR and the EER as well as easily computable formulae for the familywise error rate (FWER) of two FDR‐controlling procedures. Finally, we discuss some undesirable properties of the FDR concept, especially the problem of cheating. 相似文献
5.
A central goal in designing clinical trials is to find the test that maximizes power (or equivalently minimizes required sample size) for finding a false null hypothesis subject to the constraint of type I error. When there is more than one test, such as in clinical trials with multiple endpoints, the issues of optimal design and optimal procedures become more complex. In this paper, we address the question of how such optimal tests should be defined and how they can be found. We review different notions of power and how they relate to study goals, and also consider the requirements of type I error control and the nature of the procedures. This leads us to an explicit optimization problem with objective and constraints that describe its specific desiderata. We present a complete solution for deriving optimal procedures for two hypotheses, which have desired monotonicity properties, and are computationally simple. For some of the optimization formulations this yields optimal procedures that are identical to existing procedures, such as Hommel's procedure or the procedure of Bittman et al. (2009), while for other cases it yields completely novel and more powerful procedures than existing ones. We demonstrate the nature of our novel procedures and their improved power extensively in a simulation and on the APEX study (Cohen et al., 2016). 相似文献
6.
In a typical clinical trial, there are one or two primary endpoints, and a few secondary endpoints. When at least one primary endpoint achieves statistical significance, there is considerable interest in using results for the secondary endpoints to enhance characterization of the treatment effect. Because multiple endpoints are involved, regulators may require that the familywise type I error rate be controlled at a pre-set level. This requirement can be achieved by using \"gatekeeping\" methods. However, existing methods suffer from logical oddities such as allowing results for secondary endpoint(s) to impact the likelihood of success for the primary endpoint(s). We propose a novel and easy-to-implement gatekeeping procedure that is devoid of such deficiencies. A real data example and simulation results are used to illustrate efficiency gains of our method relative to existing methods. 相似文献
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Li J 《Biometrical journal. Biometrische Zeitschrift》2011,53(5):797-809
Major objectives of a clinical trial are commonly stated in a hierarchical order as primary and secondary. The parallel gatekeeping testing strategy provides an opportunity to assess secondary objectives when all or partial primary objectives are achieved. The current available gatekeeping procedures have different pros and cons so users either need to justify the assumption associated with some procedures or tolerate suboptimal power performance of other procedures. By applying the Holm test with a flexible alpha splitting technique, we propose a procedure which (1) is powerful for assessing the primary objectives, (2) can be used when no assumption can be made on the dependency structure of test statistics, and (3) has the full flexibility to allocate user-preferred alpha to assess the secondary objectives based on the number of primary objectives achieved. A real clinical trial example is used for illustration of the proposed procedure. 相似文献
9.
本文讨论了一类具有强连续时滞的捕食-被捕食模型,分析了各非负平衡点的稳定性,利用区域连续收缩方法,得出非负平衡点全局稳定的充分条件,给出正平衡点全局稳定的充分条件,并给出系统出现Hopf的分支值． 相似文献
10.
In many applications where it is necessary to test multiple hypotheses simultaneously, the data encountered are discrete. In such cases, it is important for multiplicity adjustment to take into account the discreteness of the distributions of the p‐values, to assure that the procedure is not overly conservative. In this paper, we review some known multiple testing procedures for discrete data that control the familywise error rate, the probability of making any false rejection. Taking advantage of the fact that the exact permutation or exact pairwise permutation distributions of the p‐values can often be determined when the sample size is small, we investigate procedures that incorporate the dependence structure through the exact permutation distribution and propose two new procedures that incorporate the exact pairwise permutation distributions. A step‐up procedure is also proposed that accounts for the discreteness of the data. The performance of the proposed procedures is investigated through simulation studies and two applications. The results show that by incorporating both discreteness and dependency of p‐value distributions, gains in power can be achieved. 相似文献
11.
Sue‐Jane Wang H. M. James Hung Robert T. O'Neill 《Biometrical journal. Biometrische Zeitschrift》2009,51(2):358-374
The utility of clinical trial designs with adaptive patient enrichment is investigated in an adequate and well‐controlled trial setting. The overall treatment effect is the weighted average of the treatment effects in the mutually exclusive subsets of the originally intended entire study population. The adaptive enrichment approaches permit assessment of treatment effect that may be applicable to specific nested patient (sub)sets due to heterogeneous patient characteristics and/or differential response to treatment, e.g. a responsive patient subset versus a lack of beneficial patient subset, in all patient (sub)sets studied. The adaptive enrichment approaches considered include three adaptive design scenarios: (i) total sample size fixed and with futility stopping, (ii) sample size adaptation and futility stopping, and (iii) sample size adaptation without futility stopping. We show that regardless of whether the treatment effect eventually assessed is applicable to the originally studied patient population or only to the nested patient subsets; it is possible to devise an adaptive enrichment approach that statistically outperforms one‐size‐fits‐all fixed design approach and the fixed design with a pre‐specified multiple test procedure. We emphasize the need of additional studies to replicate the finding of a treatment effect in an enriched patient subset. The replication studies are likely to need fewer number of patients because of an identified treatment effect size that is larger than the diluted overall effect size. The adaptive designs, when applicable, are along the line of efficiency consideration in a drug development program. 相似文献
12.
Qian H. Li 《Biometrical journal. Biometrische Zeitschrift》2009,51(1):137-145
Often a treatment is assessed by co‐primary endpoints so that a comprehensive picture of the treatment effect can be obtained. Co‐primary endpoints can be different medical assessments angled at different aspects of a disease, therefore, are used collectively to strengthen evidence for the treatment effect. It is common sense that if a treatment is ineffective, the chance to show that the treatment is effective in all co‐primary endpoints should be small. Therefore, it may not be necessary to require all the co‐primary endpoints to be statistically significant at the 1‐sided 0.025 level to control the error rate of wrongly approving an ineffective treatment. Rather it is reasonable to allow certain variation for the p ‐values within a range close to 0.025. In this paper, statistical methods are developed to derive decision rules to evaluate co‐primary endpoints collectively. The decision rules control the error rate of wrongly accepting an ineffective treatment at the level of 0.025 for a study and the error rate at a slightly higher level for a treatment that works for all the co‐primary endpoints except perhaps one. The decision rules also control the error rates for individual endpoints. Potential applications in clinical trials are presented (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim) 相似文献
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Multiple endpoints are tested to assess an overall treatment effect and also to identify which endpoints or subsets of endpoints contributed to treatment differences. The conventional p‐value adjustment methods, such as single‐step, step‐up, or step‐down procedures, sequentially identify each significant individual endpoint. Closed test procedures can also detect individual endpoints that have effects via a step‐by‐step closed strategy. This paper proposes a global‐based statistic for testing an a priori number, say, r of the k endpoints, as opposed to the conventional approach of testing one (r = 1) endpoint. The proposed test statistic is an extension of the single‐step p‐value‐based statistic based on the distribution of the smallest p‐value. The test maintains strong control of the FamilyWise Error (FWE) rate under the null hypothesis of no difference in any (sub)set of r endpoints among all possible combinations of the k endpoints. After rejecting the null hypothesis, the individual endpoints in the sets that are rejected can be tested further, using a univariate test statistic in a second step, if desired. However, the second step test only weakly controls the FWE. The proposed method is illustrated by application to a psychosis data set. 相似文献
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Different coastal areas possess different pollution risks and ecosystem service values. The management strategies in these areas also differ. With limited environmental funds available, it is necessary to conduct in-depth study of pollution risks and ecosystem service values for developing marine conservation and management strategies. This paper proposes a management method that combines marine pollution risks and ecosystem service values to identify the management priorities of different sites, which are used to determine the appropriate management strategies. The management priorities of different bays in China's Bohai Sea were determined, and management strategies were recommended. The method can be used to determine effective management strategies for oceans around the world, especially in developing countries with limited environmental protection funds. 相似文献
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Fariborz Nasertorabi Andres Alonso Scott W. Rogers Tomas Mustelin Kristiina Vuori Lars Liljas Kathryn R. Ely 《Acta Crystallographica. Section F, Structural Biology Communications》2005,61(2):174-177
Cas‐family proteins serve as docking proteins in integrin‐mediated signal transduction. The founding member of this family, p130Cas, becomes tyrosine‐phosphorylated in response to extracellular stimuli such as integrin‐mediated cell adhesion and ligand engagement of receptor tyrosine kinases. Cas proteins are large multidomain molecules that transmit signals as intermediaries through interactions with signaling molecules such as FAK and other tyrosine kinases, as well as tyrosine phosphatases. After Cas is tyrosine‐phosphorylated, it acts as a docking protein for binding SH2 domains of Src‐family kinases. In order to examine the structural basis for a key step in propagation of signals by Cas, one of the major SH2‐binding sites of Cas has been crystallized in complex with the SH3‐SH2 regulatory domains of the Src‐family kinase Lck. Crystallization conditions were identified by high‐throughput screening and optimized with multiple rounds of seeding. The crystals formed at 295 K in space group P212121, with unit‐cell parameters a = 77.4, b = 107.3, c = 166.4 Å, and diffract to 2.7 Å resolution. 相似文献
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Todd M. Freeberg D. L. Book Rebecca L. Weiner 《Ethology : formerly Zeitschrift fur Tierpsychologie》2016,122(1):10-19
When animals detect predators they modify their behavior to avoid predation. However, less is known about whether prey species modify their behavior in response to predator body and behavioral cues. Recent studies indicated that tufted titmice, a small songbird, decreased their foraging behavior and increased their calling rates when they detected a potential predator facing toward a feeder they were using, compared to a potential predator facing away from that feeder. Here, we tested whether related Carolina chickadees, Poecile carolinensis, were also sensitive not just to the presence of a predator model, but to its facial/head orientation. Although chickadees are closely related to titmice, recent studies in different populations suggest chickadees respond to risky contexts involving predators differently than titmice. We conducted two field studies near feeders the birds were exploiting. In Study One, a mask‐wearing human observer stood near the feeder. In Study Two, a model of a domestic cat was positioned near the feeder. In both studies, the potential threatening stimulus either faced toward or faced away from the feeder. Chickadees avoided the feeder more in both studies when the potential predator was present, and showed strongest feeder avoidance when the potential predator faced toward the feeder. Chickadee calling behavior was also affected by the facial orientation of the potential predator in Study 1. These results suggest that, like titmice, chickadees exhibit predation‐risk‐sensitive foraging and calling behavior, in relation to facial and head orientation of potential threats. These small birds seem to attend to the likely visual space of potential predators. Sensitivity to predator cues like behavior and body posture must become more central to our theories and models of anti‐predator behavioral systems. 相似文献
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Melissa M. Heintz Susanne M. Brander James W. White 《Ethology : formerly Zeitschrift fur Tierpsychologie》2015,121(5):480-491
Endocrine disrupting compounds (EDCs) enter aquatic habitats from a variety of anthropogenic sources and can mimic, block, or modulate the synthesis of natural hormones. EDCs affect both reproductive and non‐reproductive behaviors because hormones mediate responses associated with aggression and fear. We examined the effects of two EDCs on risk‐taking behaviors in guppies (Poecilia reticulata). We quantified risk‐taking in terms of propensity to forage in a risky location and tendency to join groups in the presence of a predator. We found that male and female guppies responded oppositely to environmentally relevant concentrations of an estrogenic EDC, 17α‐ethinylestradiol (EE2), or an androgenic EDC, 17β‐trenbolone (TB). Males decreased risk‐taking with increasing EE2 concentration (as predicted), but females increased risk‐taking (contrary to prediction). In contrast, females increased risk‐taking with increasing TB concentrations (as predicted), but males decreased risk‐taking (contrary to prediction). These results did not match our expectation that EE2 would reduce risk‐taking and TB would increase risk‐taking in both sexes. We suspect EE2 and TB produced these counterintuitive effects by downregulating their corresponding hormone receptors and thus reducing levels of circulating endogenous hormones in females and males, respectively. These results show that EDCs can alter fish behavior and potentially reduce fitness in unexpected ways. 相似文献
18.
Simon Eckerstrm‐Liedholm Will Sowersby Sergey Morozov Wouter van der Bijl Piotr K. Rowi&#x;ski Alejandro Gonzalez‐Voyer Bjrn Rogell 《Evolution; international journal of organic evolution》2019,73(11):2312-2323
Species with fast life‐histories typically prioritize current over future reproductive events, compared to species with slow life‐histories. These species therefore require greater energetic input into reproduction, and also likely have less time to realize their reproductive potential. Hence, behaviors that increase access to both resources and mating opportunities, at a cost of increased mortality risk, could coevolve with the pace of life‐history. However, whether this prediction holds across species, remains untested under standardized conditions. Here, we test how risky behaviors, which facilitate access to resources and mating opportunities (i.e., activity, boldness, and aggression), along with metabolic rate, coevolve with the pace of life‐history across 20 species of killifish that present remarkable divergences in the pace of life‐history. We found a positive association between the pace of life‐history and aggression, but interestingly not with other behavioral traits or metabolic rate. Aggression is linked to interference competition, and in killifishes is often employed to secure mates, while activity and boldness are more relevant for exploiting energetic resources. Our results suggest that the trade‐off between current and future reproduction plays a more prominent role in shaping mating behavior, while behaviors related to energy acquisition may be influenced by ecological factors. 相似文献
19.
We derive and compare the operating characteristics of hierarchical and square array-based testing algorithms for case identification in the presence of testing error. The operating characteristics investigated include efficiency (i.e., expected number of tests per specimen) and error rates (i.e., sensitivity, specificity, positive and negative predictive values, per-family error rate, and per-comparison error rate). The methodology is illustrated by comparing different pooling algorithms for the detection of individuals recently infected with HIV in North Carolina and Malawi. 相似文献
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Valentina Caracciolo Marcella Macaluso Luca D'Agostino Micaela Montanari Jonathan Scheff Krzysztof Reiss Kamel Khalili Antonio Giordano 《Journal of cellular biochemistry》2010,110(1):182-190
The formation and progression of mudulloblastoma (MB) is poorly understood. However, somatic inactivation of pRb/p105, in combination with a somatic or a germ‐line TP53 inactivation, leads to MB in a mouse model. Presently, there is no specific evidence of pathway/s alterations for the other two members of the retinoblastoma family, pRb2/p130 and/or p107 in MB. JC virus (JCV) is a human polyomavirus. Although there is no firm evidence that this virus plays a causal role in human neoplasia, it has been clearly proven that JCV is highly oncogenic when injected into the brain of experimental animals. The mechanism of JCV‐induced tumorigenesis is not entirely clear. However, several studies relate the oncogenic properties of JCV mainly to its early protein large T‐antigen (T‐Ag), which is able to bind and inactivate both TP53 and Rb family proteins. Here, we compared the protein expression profiles of p53, p73, pRb family proteins, and PCNA, as main regulators of cell proliferation and death, in different cell lines of mouse primitive neuroectodermal tumors (PNET), either T‐Ag‐positive or ‐negative, and in human MB cell lines. Our goal was to determine if changes in the relative expression of these regulators could trigger molecular perturbations underlying MB pathogenesis in mouse and human cells. Our results support that the presence of JCV T‐Ag may interfere with the expression of pRb family proteins, specific p73 isoforms, and p53. In turn, this “perturbation” may trigger a network of signals strictly connected with survival and apoptosis. J. Cell. Biochem. 110: 182–190, 2010. © 2010 Wiley‐Liss, Inc. 相似文献