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51.
    
In phase I trials, the main goal is to identify a maximum tolerated dose under an assumption of monotonicity in dose–response relationships. On the other hand, such monotonicity is no longer applied to biologic agents because a different mode of action from that of cytotoxic agents potentially draws unimodal or flat dose–efficacy curves. Therefore, biologic agents require an optimal dose that provides a sufficient efficacy rate under an acceptable toxicity rate instead of a maximum tolerated dose. Many trials incorporate both toxicity and efficacy data, and drugs with a variety of modes of actions are increasingly being developed; thus, optimal dose estimation designs have been receiving increased attention. Although numerous authors have introduced parametric model-based designs, it is not always appropriate to apply strong assumptions in dose–response relationships. We propose a new design based on a Bayesian optimization framework for identifying optimal doses for biologic agents in phase I/II trials. Our proposed design models dose–response relationships via nonparametric models utilizing a Gaussian process prior, and the uncertainty of estimates is considered in the dose selection process. We compared the operating characteristics of our proposed design against those of three other designs through simulation studies. These include an expansion of Bayesian optimal interval design, the parametric model-based EffTox design, and the isotonic design. In simulations, our proposed design performed well and provided results that were more stable than those from the other designs, in terms of the accuracy of optimal dose estimations and the percentage of correct recommendations.  相似文献   
52.
    
In this study we described development of boys’ and girls’ games on the school playground at recess as they progressed across the first year of primary school in London (UK) and Minneapolis (USA) in order to document age‐related trends in games during this period and to examine the predictive role of games in children's adjustment to school and more general social adjustment. Consistent with expectations, games accounted for a significant portion of children’s, but especially boys’, behavior during recess. American children played games more frequently, especially simple games, relative to English children. Consistent with expectation, the complexity of games increased, especially for boys, across the school year for children in both countries. We also examined the extent to which facility with games forecasted adjustment to school and social adjustment. Games predicted both, but only in the USA sample. Results are discussed in terms of games being an important developmental task for children of this age. Implications for future research and educational policy are discussed.  相似文献   
53.
    
Cultural pathways of identity formation have been largely unexplored. In many Asian cultures, youth are expected to concentrate on adaptation to their groups or relationships rather than pursuing their own uniqueness. Then, how do they develop a sense of identity while considering groups or relationships to be important? The purposes of this study were (a) to examine relationships between cultural self-construction (i.e. independence and interdependence) and identity processes (i.e. commitment, in-depth exploration, and reconsideration of commitment) in both societal and relational domains, and (b) to analyze the relationships of self-construction and identity processes with well-being, using a sample of Japanese emerging adults (i.e. university students and workers) aged 18–25 years. The findings indicated that relational identity was related to both independence and interdependence, whereas societal identity was mainly related to independence. Moreover, independence and identity in both societal and relational domains was positively related to well-being. Furthermore, the patterns of relationships among self-construction, identity, and well-being were found to be similar between university students and workers. These findings imply that while Japanese emerging adults have developmental needs to express one's own uniqueness, they are also directed to form a sense of identity emphasizing the maintenance of harmonious relationships with others.  相似文献   
54.
Antagonistic biological interactions with flower consumers and pathogens may influence reproductive success of flowering plants, affecting population dynamics and natural selection for floral traits. However, ecological and evolutionary consequences of the interactions may depend on both spatial and temporal patterns of the interactions. In a forest metapopulation ofPrimula sieboldii E. Morren, an endangered clonal plant species, we measured between-subpopulation patterns of seed sets and interactions with an influential flower consumer, a rove beetle,Eusphalerum bosatsu Watanabe, and a specific smut fungal pathogen,Urocystis tranzschelina (Lavrov) Zundel (Ustilaginales), for three years. Mean female fertility (seed set per flower) for individual subpopulations fluctuated moderately among years but was highly variable within each year among the five subpopulations studied. In two subpopulations, the impact ofEusphalerum beetle, was sufficiently large to result in almost complete failure in seed production over eight years including the three study and five previous preliminary observation years. In the two other subpopulations, seed set failure was caused by infection by the smut fungus. Infected capsules which constitute 10–30% of the capsules produced in the subpopulations were filled with ustilospores instead of seeds. In the subpopulation that escaped flower damage byEusphalerum beetles and smut fungal infection, seed sets of both pin and thrum flowers were much higher than in the other subpopulations. The spatial restriction of individual antagonistic agents to a part of subpopulations suggest that dispersal of the agents, as well as the mode of spatial subdivision of the plant population would be important for determining the overall effects of antagonistic interactions on plant performances at the metapopulation level.  相似文献   
55.

In this paper, we present a case study on the production planning and inventory system in a company manufacturing personal computer (PC) parts. In the case study, the targets are specified for developing a system for production planning and inventory control. The current state of the company is analysed for clarifying the points necessary to achieve the targets. Also, a system based on the analysis is proposed and its effects are estimated.  相似文献   
56.
    
Positive and negative predictive values describe the performance of a diagnostic test. There are several methods to test the equality of predictive values in paired designs. However, these methods were premised on large sample theory, and they may not be suitable for small‐size clinical trials because of inflation of the type 1 error rate. In this study, we propose an exact test to control the type 1 error rate strictly for conducting a small‐size clinical trial that investigates the equality of predictive values in paired designs. In addition, we execute simulation studies to evaluate the performance of the proposed exact test and existing methods in small‐size clinical trials. The proposed test can calculate the exact P value, and as a result of simulations, the empirical type 1 error rate for the proposed test did not exceed the significance level regardless of the setting, and the empirical power for the proposed test is not much different from the other methods based on large‐sample theory. Therefore, it is considered that the proposed exact test is useful when the type 1 error rate needs to be controlled strictly.  相似文献   
57.
Happiness is considered one of the goals of individuals and nations. Thus, many interdisciplinary efforts have attempted to determine the factors that lead to happiness. However, most of these efforts have ignored some important but less tangible factors, such as having a free press and a healthy environment. In this study, we argue that press freedom—a measure of social capital—along with human and built capital, and natural capital, predicts levels of life satisfaction across nations. Using data from 161 countries, our study provides empirical support to our theoretical model that forms of capital do not influence life satisfaction separately but are actually situated in a web of interrelationships. This is consistent with the assumptions that the road to happiness is not direct. It is a complex path where different forms of capital influence one another before leading to a happy life.  相似文献   
58.
59.
    
The phase II basket trial in oncology is a novel design that enables the simultaneous assessment of treatment effects of one anti-cancer targeted agent in multiple cancer types. Biomarkers could potentially associate with the clinical outcomes and re-define clinically meaningful treatment effects. It is therefore natural to develop a biomarker-based basket design to allow the prospective enrichment of the trials with the adaptive selection of the biomarker-positive (BM+) subjects who are most sensitive to the experimental treatment. We propose a two-stage phase II adaptive biomarker basket (ABB) design based on a potential predictive biomarker measured on a continuous scale. At Stage 1, the design incorporates a biomarker cutoff estimation procedure via a hierarchical Bayesian model with biomarker as a covariate (HBMbc). At Stage 2, the design enrolls only BM+ subjects, defined as those with the biomarker values exceeding the biomarker cutoff within each cancer type, and subsequently assesses the early efficacy and/or futility stopping through the pre-defined interim analyses. At the end of the trial, the response rate of all BM+ subjects for each cancer type can guide drug development, while the data from all subjects can be used to further model the relationship between the biomarker value and the clinical outcome for potential future research. The extensive simulation studies show that the ABB design could produce a good estimate of the biomarker cutoff to select BM+ subjects with high accuracy and could outperform the existing phase II basket biomarker cutoff design under various scenarios.  相似文献   
60.
We consider the allotment problem of homogeneous indivisible goods among agents with single-peaked and risk-averse von Neumann–Morgenstern expected utility functions. We establish that a rule satisfies coalitional strategy-proofness, same-sideness, and strong symmetry if and only if it is the uniform probabilistic rule. By constructing an example, we show that if same-sideness is replaced by respect for unanimity, this statement does not hold even with the additional requirements of no-envy, anonymity, at most binary, peaks-onlyness and continuity. We would like to thank the associate editor and two anonymous referees whose comments and suggestions significantly improve this paper. We are also grateful to Masaki Aoyagi, Kazuhiko Hashimoto, Hervé Moulin, Hiroo Sasaki, Koji Takamiya, William Thomson, Takuma Wakayama as well as other participants at the Eighth International Meeting of the Society for Social Choice and Welfare in Istanbul, the 2006 Autumn Annual Meeting of the Japanese Economic Association in Osaka, and Yokohama National University Seminar of Economic Theory for their helpful comments. We acknowledge financial supports from the Japan Society for the Promotion of Science via the Research Fellowship for Young Scientist (Hatsumi) and the Grant-in-Aid for Scientific Research (Serizawa).  相似文献   
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