The Optimal Inventory Policy with the Reusable Raw Material and Imperfect Items

This paper covers four topics regarding inventory models, namely reusable raw material, the EPQ model, imperfect-quality items, and the present value method. The relevant cost value used in traditional EPQ models does not include the stockholding cost of raw material, which makes such models unsuitable for investigating production. Because people in the world are attempting to reduce the impact of environmental impairment and increasing market competition, all products are manufactured from 100% reusable raw material and are screened during the manufacturing process. By taking the fixed proportion of imperfect-quality items and the time value into account and applying the present value method to analyze optimal inventory policies, this study creates a modified EPQ inventory model that is close to real life we meet. Furthermore, this model aims to promote the reputation of a company and ascertain its costs accurately

ESTIMATION IN A PROPORTIONAL HAZARD MODEL FOR SEMI-MARKOV COUNTING PROCESS

Abstract: Estimation is studied in a regression model for counting processes whose baseline intensity processes are of semi-Markov form. Asymptotic normality is established for a Breslow-type estimator of the cumulative baseline hazard for each gap time of the counting process

Tissue microarray analysis reveals a tight correlation between protein expression pattern and progression of esophageal squamous cell carcinoma

BACKGROUND: The development of esophageal squamous cell carcinoma (ESCC) progresses a multistage process, collectively known as precursor lesions, also called dysplasia (DYS) and carcinoma in situ (CIS), subsequent invasive lesions and final metastasis. In this study, we are interested in investigating the expression of a variety of functional classes of proteins in ESCC and its precursor lesions and characterizing the correlation of these proteins with ESCC malignant progression. METHODS: Fas, FADD, caspase 8, CDC25B, fascin, CK14, CK4, annexin I, laminin-5γ2 and SPARC were analyzed using immunohistochemistry on tissue microarray containing 205 ESCC and 173 adjacent precursor lesions as well as corresponding normal mucosa. To confirm the immunohistochemical results, three proteins, fascin, CK14 and laminin-5γ2, which were overexpressed in ESCC on tissue microarray, were detected in 12 ESCC cell lines by Western blot assay. RESULTS: In ESCC and its precursor lesions, FADD, CDC25B, fascin, CK14, laminin-5γ2 and SPARC were overexpressed, while Fas, caspase 8, CK4 and annexin I were underexpressed. The abnormalities of these proteins could be classified into different groups in relation to the stages of ESCC development. They were "early" corresponding to mild and moderate DYS with overexpression of fascin, FADD and CDC25B and underexpression of Fas, caspase 8, CK4 and annexin I, "intermediate" to severe DYS and CIS with overexpression of FADD and CK14, and "late" to invasive lesions (ESCC) and to advanced pTNM stage ESCC lesions with overexpression of CK14, laminin-5γ2 and SPARC. CONCLUSION: Analyzing the protein expression patterns of Fas, FADD, caspase 8, CDC25B, fascin, CK14, CK4, annexin I, laminin-5γ2 and SPARC would be valuable to develop rational strategies for early detection of lesions at risk in advance as well as for prevention and treatment of ESCC

Lot-to-lot consistency study of an Escherichia coli -produced bivalent human papillomavirus vaccine in adult women: a randomized trial.

An Escherichia. coli -produced HPV-16/18 bivalent vaccine has been proved to be well-tolerated and highly efficacious against diseases associated with vaccine HPV types. As a part of the multi-center, randomized, double-blind phase III clinical trial, this lot-to-lot consistency study aimed to assess the safety and immunogenicity consistency of this novel HPV vaccine, which is also one of the objectives of the phase III trial. A total of 3689 healthy women aged 18-45 years were enrolled and randomly assigned 1:1:1 to three lots of the HPV vaccine groups. The primary outcomes were the IgG antibody level at 1 month after the last dose (month 7). In the immunogenicity per-protocol set (PPS), almost all of the participants seroconverted at month 7 and remained seropositive at month 42. For each paired comparison of the three lot groups, the two-sides of 90% CIs of GMC ratios for both IgG and neutralizing antibodies for HPV-16 and HPV-18 at month 7 were within the equivalence interval [0.5, 2]. Lot consistency was also demonstrated at month 42. The majority of recorded solicited reactions were mild or moderate. The incidences of solicited reactions of Lot 2 and Lot 3 were slightly higher than Lot 1. However, the incidences of solicited reactions of ≥ grade 3 and solicited reactions by symptoms were all similar among the three lot groups. None of the SAEs was considered related to vaccination by the investigator. In conclusion, this study demonstrates lot-to-lot consistency of the 3 consecutive lots of the E. coli -produced HPV-16/18 bivalent vaccine

Efficacy, Safety, and Immunogenicity of an Escherichia coliProduced Bivalent Human Papillomavirus Vaccine: An Interim Analysis of a Randomized Clinical Trial

HPV是一种常见的生殖道感染病毒，高危型HPV持续性感染能够导致几乎所有的宫颈癌，其中HPV 16型和18型危害最大，可导致约70%的宫颈癌。预防性HPV疫苗有望减少甚至最终消灭由疫苗型别导致的宫颈癌，降低HPV相关的疾病负担。该研究是在全国4个中心5个现场的18-45岁健康女性中进行的多中心、随机、双盲、对照（戊肝疫苗）的三期临床试验，该研究结果证实我校自主研发的双价人乳头瘤病毒疫苗（大肠杆菌）具有良好的安全性、免疫原性和免疫持久性，可有效地预防HPV 16型和/或18型相关的宫颈高度癌前病变及持续性感染。 该论文报告了我校和厦门万泰沧海生物技术有限公司自主研发的双价人乳头瘤病毒疫苗（大肠杆菌）三期临床试验的期中分析结果。这是第一个进入临床试验并提交药品注册申请的国产人乳头瘤病毒疫苗（HPV疫苗），有望成为世界上第四个上市的HPV疫苗，受到世界卫生组织和盖茨基金会等国际组织的高度关注。 中国医学科学院肿瘤医院乔友林教授、我校吴婷教授、广西壮族自治区疾病预防控制中心李荣成主任医师、江苏省疾病预防控制中心胡月梅主任医师、北京大学人民医院魏丽惠教授、中国食品药品检定研究院李长贵研究员、中国医学科学院肿瘤医院陈汶教授为该论文的共同第一作者，我校张军教授、夏宁邵教授和中国医学科学院肿瘤医院乔友林教授为该论文的共同通讯作者。【Abstract】Background The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase 3 clinical trial was conducted to evaluate the efficacy, safety and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine. Methods A multi-centre, randomized, double-blind trial started on November 22, 2012, in China. In total, 7372 eligible women aged 18-45 years were age-stratified and randomly assigned to receiving 3 doses of the test or control (hepatitis E) vaccine at months 0, 1 and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received 3 doses of the vaccine. This report presents data from a pre-specified interim analysis used for regulatory submission. Results In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval [CI] = 55.6% to 100.0%, 0/3306 in the vaccine group vs. 10/3296 in the control group) and 97.8% (95% CI = 87.1% to 99.9%, 1/3240 vs. 45/3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months. Conclusions The Escherichia coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18 associated high-grade genital lesions and persistent infection in women.This work was supported by grants from the Chinese National High-tech R&D Program (863 program, 2012AA02A408), the Chinese National Major Scientific and Technological Special Project for “Significant New Drug Development” (2018ZX09308010 and 2012ZX09101316), the National Natural Science Foundation of China (81673240 and U1705283), the Fujian Provincial Major Scientific and Technological Project (2015YZ0002), the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS, 2017-I2M-B&R-03, and 2016-I2M-1-019) and Xiamen Innovax. 该研究获得了国家高技术研究发展计划（863计划）、新药创制国家科技重大专项、国家自然科学基金、福建省科技重大专项、中国医学科学院医学与健康科技创新工程基金以及厦门万泰沧海生物技术有限公司的资助