The concrete arch bridge is a natural and appropriate structural solution,aesthetically pleasing and easily integrated into the environment,especially in mountainous and island areas.However,construction difficulty an...The concrete arch bridge is a natural and appropriate structural solution,aesthetically pleasing and easily integrated into the environment,especially in mountainous and island areas.However,construction difficulty and cost will increase with heavy self-weight when the span enlarges.A potential solution is to use a composite box arch ring with steel web-concrete flange.Taking Wanzhou Yangtze River Bridge(the longest concrete arch bridge in the world with a main span of 420 m)as a prototype,trial designs of a composite box arch with steel webs(including corrugated steel webs and plain steel webs)and concrete flanges were carried out.Comparison of quantities and structural behaviors of the prototype concrete arch with the two trial designed composite arch was presented.It is shown that the selfweight of the composite arch can reduce about 28%and the structures can meet the design requirements,therefore it is possible to use the two composite arches in long span arch bridges.展开更多
Let G be a non-abelian group and let l2(G) be a finite dimensional Hilbert space of all complex valued functions for which the elements of G form the (standard) orthonormal basis. In our paper we prove results concern...Let G be a non-abelian group and let l2(G) be a finite dimensional Hilbert space of all complex valued functions for which the elements of G form the (standard) orthonormal basis. In our paper we prove results concerning G-decorrelated decompositions of functions in l2(G). These G-decorrelated decompositions are obtained using the G-convolution either by the irreducible characters of the group G or by an orthogonal projection onto the matrix entries of the irreducible representations of the group G. Applications of these G-decorrelated decompositions are given to crossover designs in clinical trials, in particular the William’s 6×3?design with 3 treatments. In our example, the underlying group is the symmetric group S3.展开更多
AIM:To present statistical tools to model and optimize the cost of a randomized clinical trial as a function of the stringency of patient inclusion criteria.METHODS: We consider a two treatment, dichotomous outcome tr...AIM:To present statistical tools to model and optimize the cost of a randomized clinical trial as a function of the stringency of patient inclusion criteria.METHODS: We consider a two treatment, dichotomous outcome trial that includes a proportion of patients who are strong responders to the tested intervention. Patients are screened for inclusion using an arbitrary number of test results that are combined into an aggregate suitability score. The screening score is regarded as a diagnostic test for the responsive phenotype, having a specific cutoff value for inclusion and a particular sensitivity and specificity. The cutoff is a measure of stringency of inclusion criteria. Total cost is modeled as a function of the cutoff value, number of patients screened, the number of patients included, the case occurrence rate, response probabilities for control and experimental treatments, and the trial duration required to produce a statistically significant result with a specified power. Regression methods are developed to estimate relevant model parameters from pilot data in an adaptive trial design. RESULTS: The patient numbers and total cost are strongly related to the choice of the cutoff for inclusion. Clear cost minimums exist between 5.6 and 6.1 on arepresentative 10-point scale of exclusiveness. Potential cost savings for typical trial scenarios range in millions of dollars. As the response rate for controls approaches 50%, the proper choice of inclusion criteria can mean the difference between a successful trial and a failed trial. CONCLUSION: Early formal estimation of optimal inclusion criteria allows planning of clinical trials to avoid high costs, excessive delays, and moral hazards of Type II errors.展开更多
Various adaptive designe have been proposed and applied to clinical trials,bioassay,psycho-physics,etc.Adaptive designs are also useful in high cost engineering trials.More and More people have been paying attention t...Various adaptive designe have been proposed and applied to clinical trials,bioassay,psycho-physics,etc.Adaptive designs are also useful in high cost engineering trials.More and More people have been paying attention to these desing methods.This paper introduces several broad families of designs,such as the play-the-winner rele,randomized play-the-winner rule and its generalization to the multi-arm case,doubly bi-ased coin adaptive design,Markov chain model.展开更多
The implementation of molecular profiling technologies in oncology deepens our knowledge for the molecular landscapes of cancer diagnoses, identifying aberrations that could be linked with specific therapeutic vulnera...The implementation of molecular profiling technologies in oncology deepens our knowledge for the molecular landscapes of cancer diagnoses, identifying aberrations that could be linked with specific therapeutic vulnerabilities. In particular, there is an increasing list of molecularly targeted anticancer agents undergoing clinical development that aim to block specific molecular aberrations. This leads to a paradigm shift, with an increasing list of specific aberrations dictating the treatment of patients with cancer. This paradigm shift impacts the field of clinical trials, since the classical approach of having clinico-pathological disease characteristics dictating the patients' enrolment in oncology trials shifts towards the implementation of molecular profiling as prescreening step. In order to facilitate the successful clinical development of these new anticancer drugs within specific molecular niches of cancer diagnoses, there have been developed new, innovative trial designs that could be classified as follows: i)longitudinal cohort studies that implement(or not) "nested" downstream trials, 2) studies that assess the clinical utility of molecular profiling, 3) "master" protocol trials, iv) "basket" trials, v) trials following an adaptive design. In the present article, we review these innovative study designs, providing representative examples from each category and we discuss the challenges that still need to be addressed in this era of new generation oncology trials implementing molecular profiling. Emphasis is put on the field of breast cancer clinical trials.展开更多
基金This work was supported by the International Science and Technology Cooperation Projects(No.2009DFA72220)Shanghai Post-Doctoral Projects(No.10R21416100).
文摘The concrete arch bridge is a natural and appropriate structural solution,aesthetically pleasing and easily integrated into the environment,especially in mountainous and island areas.However,construction difficulty and cost will increase with heavy self-weight when the span enlarges.A potential solution is to use a composite box arch ring with steel web-concrete flange.Taking Wanzhou Yangtze River Bridge(the longest concrete arch bridge in the world with a main span of 420 m)as a prototype,trial designs of a composite box arch with steel webs(including corrugated steel webs and plain steel webs)and concrete flanges were carried out.Comparison of quantities and structural behaviors of the prototype concrete arch with the two trial designed composite arch was presented.It is shown that the selfweight of the composite arch can reduce about 28%and the structures can meet the design requirements,therefore it is possible to use the two composite arches in long span arch bridges.
文摘Let G be a non-abelian group and let l2(G) be a finite dimensional Hilbert space of all complex valued functions for which the elements of G form the (standard) orthonormal basis. In our paper we prove results concerning G-decorrelated decompositions of functions in l2(G). These G-decorrelated decompositions are obtained using the G-convolution either by the irreducible characters of the group G or by an orthogonal projection onto the matrix entries of the irreducible representations of the group G. Applications of these G-decorrelated decompositions are given to crossover designs in clinical trials, in particular the William’s 6×3?design with 3 treatments. In our example, the underlying group is the symmetric group S3.
文摘AIM:To present statistical tools to model and optimize the cost of a randomized clinical trial as a function of the stringency of patient inclusion criteria.METHODS: We consider a two treatment, dichotomous outcome trial that includes a proportion of patients who are strong responders to the tested intervention. Patients are screened for inclusion using an arbitrary number of test results that are combined into an aggregate suitability score. The screening score is regarded as a diagnostic test for the responsive phenotype, having a specific cutoff value for inclusion and a particular sensitivity and specificity. The cutoff is a measure of stringency of inclusion criteria. Total cost is modeled as a function of the cutoff value, number of patients screened, the number of patients included, the case occurrence rate, response probabilities for control and experimental treatments, and the trial duration required to produce a statistically significant result with a specified power. Regression methods are developed to estimate relevant model parameters from pilot data in an adaptive trial design. RESULTS: The patient numbers and total cost are strongly related to the choice of the cutoff for inclusion. Clear cost minimums exist between 5.6 and 6.1 on arepresentative 10-point scale of exclusiveness. Potential cost savings for typical trial scenarios range in millions of dollars. As the response rate for controls approaches 50%, the proper choice of inclusion criteria can mean the difference between a successful trial and a failed trial. CONCLUSION: Early formal estimation of optimal inclusion criteria allows planning of clinical trials to avoid high costs, excessive delays, and moral hazards of Type II errors.
文摘Various adaptive designe have been proposed and applied to clinical trials,bioassay,psycho-physics,etc.Adaptive designs are also useful in high cost engineering trials.More and More people have been paying attention to these desing methods.This paper introduces several broad families of designs,such as the play-the-winner rele,randomized play-the-winner rule and its generalization to the multi-arm case,doubly bi-ased coin adaptive design,Markov chain model.
文摘The implementation of molecular profiling technologies in oncology deepens our knowledge for the molecular landscapes of cancer diagnoses, identifying aberrations that could be linked with specific therapeutic vulnerabilities. In particular, there is an increasing list of molecularly targeted anticancer agents undergoing clinical development that aim to block specific molecular aberrations. This leads to a paradigm shift, with an increasing list of specific aberrations dictating the treatment of patients with cancer. This paradigm shift impacts the field of clinical trials, since the classical approach of having clinico-pathological disease characteristics dictating the patients' enrolment in oncology trials shifts towards the implementation of molecular profiling as prescreening step. In order to facilitate the successful clinical development of these new anticancer drugs within specific molecular niches of cancer diagnoses, there have been developed new, innovative trial designs that could be classified as follows: i)longitudinal cohort studies that implement(or not) "nested" downstream trials, 2) studies that assess the clinical utility of molecular profiling, 3) "master" protocol trials, iv) "basket" trials, v) trials following an adaptive design. In the present article, we review these innovative study designs, providing representative examples from each category and we discuss the challenges that still need to be addressed in this era of new generation oncology trials implementing molecular profiling. Emphasis is put on the field of breast cancer clinical trials.
