A Quality Risk Management Model Approach for Cell Therapy Manufacturing

International regulatory authorities view risk management as an essential production need for the development of innovative, somatic cell‐based therapies in regenerative medicine. The available risk management guidelines, however, provide little guidance on specific risk analysis approaches and procedures applicable in clinical cell therapy manufacturing. This raises a number of problems. Cell manufacturing is a poorly automated process, prone to operator‐introduced variations, and affected by heterogeneity of the processed organs/tissues and lot‐dependent variability of reagent (e.g., collagenase) efficiency. In this study, the principal challenges faced in a cell‐based product manufacturing context (i.e., high dependence on human intervention and absence of reference standards for acceptable risk levels) are identified and addressed, and a risk management model approach applicable to manufacturing of cells for clinical use is described for the first time. The use of the heuristic and pseudo‐quantitative failure mode and effect analysis/failure mode and critical effect analysis risk analysis technique associated with direct estimation of severity, occurrence, and detection is, in this specific context, as effective as, but more efficient than, the analytic hierarchy process. Moreover, a severity/occurrence matrix and Pareto analysis can be successfully adopted to identify priority failure modes on which to act to mitigate risks. The application of this approach to clinical cell therapy manufacturing in regenerative medicine is also discussed.     

Opportunities of the minimum Anderson–Darling estimator as a variant of the maximum likelihood method

We reveal that the minimum Anderson–Darling (MAD) estimator is a variant of the maximum likelihood method. Furthermore, it is shown that the MAD estimator offers excellent opportunities for parameter estimation if there is no explicit formulation for the distribution model. The computation time for the MAD estimator with approximated cumulative distribution function is much shorter than that of the classical maximum likelihood method with approximated probability density function. Additionally, we research the performance of the MAD estimator for the generalized Pareto distribution and demonstrate a further advantage of the MAD estimator with an issue of seismic hazard analysis.     

Linearity of regression for non-adjacent record values

Let X₁,X₂,… be a sequence of iid random variables having a continuous distribution; by R₁,R₂,… denote the corresponding record values. All the distributions allowing linearity of regressions either E(R_m+k|R_m) or E(R_m|R_m+k) are identified.     

京郊乡镇企业产权结构分析与发展思考

文章分析了京郊乡镇企业产权多元化格局 ,并指出产权多元化后所存在的问题 ,针对存在问题 ,提出建立有效的集体资产运营机制、优化企业治理结构、切实转变政府职能等应对策略     

新时期大学生社团文化活动

高校社团的文化活动是大学生自我教育的第二课堂,是大学生素质拓展的重要环节,是大学生了解社会的重要桥梁.从新时期文化建设的战略意义出发,分析了高校大学生社团的文化活动有待加强的六个方面.并针对以上情况提出了大学生社团活动体现文化先进性要求的对策,即做到"四个结合". 认为,发现新时期大学生杜团文化活动存在的问题并提出相应的是开展社团活动、弘扬先进文化的重要举措之一.     

二阶段供应链中提前期压缩的影响与协调

提前期是衡量业务过程绩效一个重要的因素,基于时间竞争的供应链管理战略核心就在于提前期的压缩,提前期压缩是形成供应链战略优势的有力来源.在市场需求预测精度随提前期变化的假设下,采用逻辑证明和数值分析的方法,研究由供应商-零售商构成的两阶段供应链中提前期压缩对供应链及其成员收益的影响以及如何实现供应链的渠道协调.研究结果表明:当供应链的服务水平小于0.5时,提前期的压缩可以获得供应链成员收益的Pareto改进;当供应链的服务水平大于等于0.5,引入线性转移支付补偿机制,可以实现供应链的渠道协调,获得供应链成员收益的Pareto改进.     

ROBUSTNESS OF PROCEDURES FOR THE BEHRENS-FISHER PROBLEMS: EXTENSION TO BIVARIATE NORMAL MIXTURES

In the applied sciences, it is often important to be able to compare the mean values of two populations. However, testing a hypothesis can be complex, if the two populations are heteroscedastic and exhibit non-normality in the data. This paper reviews currently available strategies for the multivariate Behrens-Fisher problem. It then carries out Monte Carlo comparisons of selected procedures to assess their robustness when applied to data from normal mixture distributions. The overall conclusion is that Johansen's procedure appears to work best for small sample data both in terms of empirical power and significance level. Johansen's procedure works reasonably well even with mixture data. The simulation also provides researchers with specific guidelines to follow at the early designing and planning stages of the investigation.     

非单调二元非线性算子方程组的迭代求解

利用锥与半序理论和混合单调算子理论 ,讨论 Banach空间中非单调二元非线性算子方程组解的存在性与唯一性 ,并给出收敛于方程组解的迭代序列和误差估计 ,改进和推广了混合单调算子方程和一元算子方程的某些相应结果 .     

克服制约因素 改善听力教学

听是语言学习的重要途径,是从声音信号中获取信息的主要手段。听力直接影响学习者对语言信息的接收和理解。听力的提高常受到一些主客观因素的制约。本文列举了这些不利因素并提出一些消除它们进而改善听力教学的方法。     

Estimation of scale parameters in mixture distributions

Simultaneous estimation of scale parameters is considered in mixture distributions under squared-error loss. A general class of estimators is obtained which dominates the componentwise best multiple estimators and the moment estimators. As special cases, improved estimators are obtained for the multivariate t-distribution and the p-variate Lomax distribution.