A Bayesian adaptive marker‐stratified design for molecularly targeted agents with customized hierarchical modeling

It is well known that the treatment effect of a molecularly targeted agent (MTA) may vary dramatically, depending on each patient's biomarker profile. Therefore, for a clinical trial evaluating MTA, it is more reasonable to evaluate its treatment effect within different marker subgroups rather than evaluating the average treatment effect for the overall population. The marker‐stratified design (MSD) provides a useful tool to evaluate the subgroup treatment effects of MTAs. Under the Bayesian framework, the beta‐binomial model is conventionally used under the MSD to estimate the response rate and test the hypothesis. However, this conventional model ignores the fact that the biomarker used in the MSD is, in general, predictive only for the MTA. The response rates for the standard treatment can be approximately consistent across different subgroups stratified by the biomarker. In this paper, we proposed a Bayesian hierarchical model incorporating this biomarker information into consideration. The proposed model uses a hierarchical prior to borrow strength across different subgroups of patients receiving the standard treatment and, therefore, improve the efficiency of the design. Prior informativeness is determined by solving a “customized” equation reflecting the physician's professional opinion. We developed a Bayesian adaptive design based on the proposed hierarchical model to guide the treatment allocation and test the subgroup treatment effect as well as the predictive marker effect. Simulation studies and a real trial application demonstrate that the proposed design yields desirable operating characteristics and outperforms the existing designs

Research on maintenance decision making based on vibration data

Based on vibration data monitoring, by factors including vibration intensity and fault probability, system health state can be characterized, factors’ weight coefficients can be calculated, and health state function can be established, which are formal representation of system health state. Health state is divided into five levels, each level obtains its membership function by analyzing the characteristic of each factor. Using system health state as input of maintenance decision-making, predictive maintenance decision can be established. Good maintenance decision can efficiently reduce the maintenance cost and improve system availability. In this thesis, research on function expression of system health state based on vibration data was conducted. Then, using opportunity-group maintenance function based on system health state, maintenance decision was made

Lyapunov-type inequalities for fractional differential equations

The principal aim of this paper is to discuss Lyapunov-type inequalities for fractional differential equations with fractional boundary conditions. Some new Lyapunov's inequalities are established, which almost generalize and improve some earlier results in the literature

Opial type inequalities for conformable fractional derivative and integral of two functions

In this paper, we establish the Opial type inequalities for conformable fractional derivative and integral of two function and give some results in special cases of alpha

High-density Vero cell perfusion culture in BioBLU 5p Single-Use Vessels

Vero cells are anchorage-dependent cells that are widely used as a platform for viral vaccine production. In stirred-tank bioreactors, they are ordinarily grown on microcarriers. Fibra-Cel® disks are a promising alternative attachment matrix with a high surface-to-volume ratio. They provide a three-dimensional environment that protects cells from damaging shear forces, helping to achieve high cell densities. In this study, we cultivated Vero cells in Eppendorf BioBLU 5p Single-Use Vessels pre-packed with Fibra-Cel. The process was controlled with a BioFlo® 320 bioprocess control station. We cultivated the cells in perfusion mode, which ensures a consistent supply of nutrients and the removal of toxic byproducts. We achieved the very high Vero cell density of approximately 43 million cells per mL, demonstrating great potential for Vero-cell-based vaccine production using Fibra-Cel packed-bed vessels