Antibody-Drug Conjugates (ADCs): Navigating Four Pillars of Safety, Development, Supply Chain and Manufacturing Excellence

Antibody-drug conjugates (ADCs) are pioneering biologics that merge antibodies’ specificity with small molecules’ potency. With a handful of FDA-approved ADCs in the market and many under development, ADCs are poised to revolutionize therapeutics. This paper examines the complexities of ADC production, emphasizing the importance of process characterization and the pivotal role of supply chain characteristics, safety requirements, and Contract Manufacturing Organizations (CMOs) with proficiency. The swift transition of antibody-drug conjugate (ADC) programs from early to advanced clinical stages underscores the urgency for quick and efficient commercial launch preparation. This article delves into strategies to hasten commercial readiness, supply chain strategy, the significance of partnering with adept contract development and manufacturing organizations (CDMOs), and the challenges of ADC production.

Effects of proton pump inhibitors on inflammatory bowel disease:An updated review

Inflammatory bowel disease(IBD)is believed to be caused by various factors,including abnormalities in disease susceptibility genes,environmental factors,immune factors,and intestinal bacteria.Proton pump inhibitors(PPIs)are the primary drugs used to treat acid-related diseases.They are also commonly prescribed to patients with IBD.Recent studies have suggested a potential association between the use of certain medications,such as PPIs,and the occurrence and progression of IBD.In this review,we summarize the potential impact of PPIs on IBD and analyze the underlying mechanisms.Our findings may provide insights for conducting further investigations into the effects of PPIs on IBD and serve as an important reminder for physicians to exercise caution when prescribing PPIs to patients with IBD.

基于S-CAD方法的安全生产治本攻坚政策评估

国务院安委会牵头发布《安全生产治本攻坚三年行动方案(2024—2026年)》(简称“总政策”),为此,各部门制定了31个部门子方案及部分省级行动实施方案(简称“子政策”),从而形成“1+31+N”的安全生产治本攻坚总体方案。论文运用S-CAD方法和NVivo12 Plus软件,对上述政策文本开展量化政策评估。通过系统梳理从目标到结果的逻辑链条,研究发现,总政策与子政策在目标与手段、手段与价值观/立场存在逻辑上的高度一致性,手段对目标的实现上存在较强充分性。在行动方案实施过程中,需要聚焦总政策与子政策的衔接性、政策工具选择的多样性、治理目标的一致性,树立本质安全理念,坚持政府间多部门以及政府、市场与社会多主体双向协同治理,采取行政、市场、法律、社会等多种政策工具,建立事前预防型公共安全治理模式,推进高质量发展和高水平安全良性互动,实现安全生产治理体系和治理能力现代化。

TN-S系统在变电站工程安全评估中的应用

阐述变电站施工用电特点,分析TN-S系统在变电站施工用电中的安全性能评估方法,包括电气参数分析方法、电气保护方法和安全操作方法,并对该系统的安全性能进行全面评估。

基于西门子S7 Safety技术的烟厂物流安全系统

针对烟企物流系统安全性问题,介绍了一种基于西门子S7 Safety技术的物流安全系统,给出相关安全控制程序编写流程。

基于物联网的建设工程施工安全D-S诊断研究

针对建筑业生产安全事故频发且传统施工安全诊断方法准确率不高的问题,基于物联网技术在建设工程施工安全应用的优势,构建了建设工程施工安全诊断指标体系,采取AHP-熵权法组合赋权的方式确定了诊断指标权重。建立了基于D-S证据理论的施工安全诊断模型,并经案例分析验证了模型的有效性,为建筑企业安全管控和事故预防提供依据。

导叶翼型优化对水泵水轮机“S”特性的影响

为了改善水泵水轮机“S”特性,本文以某水泵水轮机模型机为研究对象,采用SST k-ω湍流模型开展水泵水轮机全流道三维数值计算。通过优化活动导叶翼型,得出n 11-Q 11模拟曲线和机组“S”特性改善情况,并对优化活动导叶翼型后的机组的无叶区进行了压力脉动分析。结果表明:优化活动导叶翼型对机组的“S”特性存在一定改善效果;翼型优化后机组的效率虽然有小幅度下降,但是整体效率依然保持在90%以上;无叶区压力脉动主要是由活动导叶区域出流,转轮叶片工作面发生冲击导致的分流以及转轮叶片与活动导叶组成的动静叶栅干涉效应引起的。改型后的活动导叶降低了无叶区的压力脉动幅值,在一定程度上提升了水泵水轮机的安全系数。

融合改进D-S理论与贝叶斯网络的机场旅客风险研究

为提高机场旅客风险评估准确性,实现分类安检的高效运行,提出了基于融合改进D-S理论和贝叶斯网络的旅客风险评估方法。首先,在识别旅客历史背景、面部情绪、异常行为的影响因素的基础上,建立旅客风险评价指标体系;然后,基于专家评价及文献统计方法,建立融合改进的D-S理论和贝叶斯网络模型以评价旅客风险;最后,通过实际案例计算各指标权重及风险值,在风险推理的基础上得出旅客风险等级,根据敏感性分析得到影响旅客风险的核心因素。结果表明,案例中的旅客为高风险等级,并且安检人员在对旅客风险分类时应重点审查托运行李违禁品记录和年飞行次数,同时,提高旅客风险评估准确性还应结合旅客情绪及异常行为,综合评估旅客风险。

Systematic review: Safety of balloon assisted enteroscopy in Crohn's disease

AIM To determine the overall and comparative risk of procedure related perforation of balloon assisted enteroscopy(BAE) in Crohn's disease(CD). METHODS Systematic review(PROSPERO #CRD42015016381) of studies reporting on CD patients undergoing BAE. Seventy-three studies reporting on 1812 patients undergoing 2340 BAEs were included. Primary outcome of interest was the overall and comparative risk of procedure related perforation of diagnostic BAE in CD. Secondary outcomes of interest were risk of procedure related perforation of diagnostic double balloon enteroscopy(DBE), risk of procedure related perforation of therapeutic BAE, efficacy of stricture dilation, and clinical utility of endoscopically assessing small bowel disease activity.RESULTS Per procedure perforation rate of diagnostic BAE in CD was 0.15%(95%CI: 0.05-0.45), which was similar to diagnostic BAE for all indications(0.11%; IRR = 1.41, 95%CI: 0.28-4.50). Per procedure perforation rate of diagnostic DBE in CD was 0.12%(95%CI: 0.03-0.44), which was similar to diagnostic DBE for all indications(0.22%; IRR = 0.54, 95%CI: 0.06-0.24). Per procedure perforation rate of therapeutic BAE in CD was 1.74%(95%CI: 0.85-3.55). Eighty-six percentof therapeutic perforations were secondary to stricture dilation. Dilation was attempted in 207 patients and 30% required surgery during median follow-up of 18 months. When diagnostic BAE assessed small bowel disease activity, changes in medical therapy resulted in endoscopic improvement in 77% of patients. CONCLUSION Diagnostic BAE in CD has a similar rate of perforation as diagnostic BAE for all indications and can be safely performed in assessment of mucosal healing.

On tolerability and safety of a maintenance treatment with 6-thioguanine in azathioprineor 6-mercaptopurine intolerant IBD patients

AIM: To determine the tolerability and safety profile of a low-dose maintenance therapy with 6-TG in azathioprine (AZA) or 6-mercaptopurine (6-MP) intolerant inflammatory bowel disease (IBD) patients over a treatment period of at least 1 year.METHODS: Database analysis.RESULTS: Twenty out of ninety-five (21%) patients discontinued 6-TG (mean dose 24.6 mg; mean 6-TGN level 540 pmol/8×108 RBC) within 1 year. Reasons for discontinuation were GI complaints (31%), malaise (15%)and hepatotoxicity (15%). Hematological events occurred in three patients, one discontinued treatment. In the 6-TG-tolerant group, 9% (7/75) could be classified as hepatotoxicity. An abdominal ultrasound was performed in 54% of patients, one patient had splenomegaly.CONCLUSION: The majority of AZA or 6-MP-intolerant IBD patients (79%) is able to tolerate maintenance treatment with 6-TG (dosages between 0.3 and 0.4 mg/kg per d). 6-TG may still be considered as an escape maintenance immunosuppressant in this difficult to treat group of patients, taking into account potential toxicity and efficacy of other alternatives. The recently reported hepatotoxicity is worrisome and 6-TG should therefore be administered only in prospective trials.

The Impact of Government Supervision and Consumer Purchasing Behavior on Food Safety

This paper aims at the theoretical analysis to the impact of government supervision and consumer purchasing behavior on food quality security, so as to look for safety strategies and measures to strengthen and improve the level of food safety in China. Reputation mechanism is introduced and Bayesian approach is based on, in which government supervision as well as consumer purchasing behavior is taken as crucial factors to impact on the food quality security. As to the proposed quantitative indicators, government supervision includes exposure rate, fine and etc.;at the same time, consumer purchasing behavior includes consumer’s WTP for security food and consumer expectations to food safety. Taking China’s dairy industry as an example, it makes simulation by Netlog. The results show that consumer purchasing behavior alone has little effect on the dairy companies’ decision-making to be honest or counterfeiting enterprises. However, combination government supervision with purchasing behavior has great impact, and plays very good effects on food safety.

基于T-S模糊故障树和贝叶斯网络的建筑施工风险评估模型建立及应用

作为国民经济发展的支柱产业,建筑业安全事故频发,施工安全形势严峻。为有效评估和降低建筑施工安全风险,将T-S模糊故障树和贝叶斯网络进行结合,建立一种建筑施工风险评估模型。利用T-S门规则和贝叶斯网络的条件概率,建立T-S模糊故障树的贝叶斯网络转化模型,引入模糊理论对事件风险概率进行模糊化,最终借助贝叶斯网络双向推理算法计算故障概率、重要度及后验概率。结果表明,该模型能够根据基本事件风险概率进行量化计算,以正向推理方式计算体系事故发生概率;能够量化根节点的模糊重要度,确定事件重点管控顺序;且可以通过反向推理计算根节点后验概率,确定故障排查顺序。该计算模型最大限度贴近实际施工情形,更加科学合理地进行建筑施工风险评估,可为建筑施工的安全风险评估和精准化管理提供理论支持。

An exploratory study of food safety and food handling: Examining ready-to-eat foods in independent delicatessen operations

The US Center for Disease Control and Prevention (CDC, 2009) reports that each year 76 million cases of foodborne illness occur with over 300,000 people hospitalized and 5000 deaths. This study, phase I of a continuing study, identifies key areas for food safety improvement. This study is designed as an exploratory evaluation of independently owned and operated delicatessen operations, using Escherichia coli and Staphylococcus aureus as indicators to assess food handling and the public’s risk for pathogenic contamination from commonly served ready-to-eat/take-away foods. The analysis consisted of a comprehensive strategy of laboratory testing of samples for pathogenic contamination, informal field observation of food handling procedures, and the examination of the most recent health inspection reports for each of the 18 operations visited. The deli turkey, cream cheese and lettuce were tested using bacteria indicator plates. The results showed widespread levels of contamination. Of the 54 samples tested for Escherichia coli, 26 showed positive results which are ~45% for E. coli contamination. Of the 54 samples tested for Staphy-lococcus aureus, 31 showed positive results which are ~57% for S. aureus contamination. One issue discovered while conducting the study was the lack of consistent uniform international standards of contamination tolerance levels. The informal field observations and health report analyses revealed widespread temperature violations and numerous instances of poor food handling. The study offers independent practitioners a strategy designed to improve their health inspections scores, food handling, and mitigation of operator liability. Independent operators traditionally do not enjoy the resources of centralized supervision and expert on-staff training;yet in aggregate they account for significant volume in both dollars and the quantity of product served. This study adds needed scrutiny to this important food niche.

基于改进YOLOX-s的安全帽检测

在施工现场中,发生过许多高空坠落事故,因此在施工现场佩戴安全帽是十分有必要的.针对安全帽佩戴状况检测中遇到的小目标样本缺检、漏检的情况,提出一种基于YOLOX-s的改进算法.首先,在Neck层引入主干特征提取网络中的160×160特征层进行特征融合,并且增加了一个针对小目标的检测头;其次,采用SIoU损失函数计算损失值,使得网络在训练过程中考虑的损失项更加全面;并且采用varifocal loss函数来计算置信度损失值,进一步改善训练过程中存在的正样本与困难样本不均衡的问题,最后,采用CA(coordinate attention)注意力机制来增强模型的特征表达能力.实验结果表明,通过对Neck层与检测层、损失函数的优化以及引入CA注意力机制,使得网络在训练过程中收敛与回归性能更佳.改进后的算法的mAP值为95.57%,相较于YOLOv3及原YOLOX-s算法在mAP值上分别提高了17.11%、3.59%.改进后的算法检测速度为54.73帧/s,符合实时检测速度要求.

全麻下机器人辅助STN-DBS治疗高龄帕金森病的经验分享

目的 分析探讨高龄(>80岁)帕金森病(PD)患者全麻下机器人辅助双侧丘脑底核脑深部刺激植入术(STN-DBS)的安全性及有效性。方法 纳入2020年6月—2021年6月于首都医科大学三博脑科医院接受全麻下机器人辅助双侧STN-DBS治疗的3例高龄PD患者,回顾性分析其临床资料、手术过程并随访评估术后6、12个月的临床症状(UPDRS-Ⅲ开、关期评估运动症状、LEDD评估用药情况、H-Y分期评估症状严重程度)、神经心理预后(HAMA评估焦虑情绪、HAMD评估抑郁情绪)、认知预后(WAIS评估智力认知)及生活质量(ADL评估生活质量)。结果 3例高龄PD患者STN-DBS手术顺利,无严重术中或术后并发症,术后靶点验证植入误差均在0.7 mm以内。术后6个月及12个月评估时,运动症状、症状严重程度、焦虑抑郁情绪、生活质量均较前有显著改善,术后用药量显著减少,神经认知功能无显著变化;6个月随访数据与12个月数据基本无显著差异。结论 全麻下机器人辅助STN-DBS对高龄PD患者有较好的临床疗效,手术安全性基本可控,术后患者运动症状、药物减量、神经心理、生活质量均有显著改善且神经认知功能总体无影响。但应同时注意高龄患者一般状况,根据患者个体状况,对高龄PD患者选择进行STN-DBS治疗。

Emerging role of dual biologic therapy for the treatment of inflammatory bowel disease

Biologic agents have now been used in the management of inflammatory bowel disease(IBD)for many years where experience,expertise and confidence in their use has developed over time.In the United Kingdom,there are well established guidelines and recommendations for both single agent biologic treatments,and with combination therapy of a biologic agent with a small molecule agent in maintenance therapy.In recent times,there has been increasing interest and experience using dual biologic therapy(DBT)in IBD,primarily in difficult to treat and refractory cases with high disease burden.However,published data on use,experience and safety profiles is limited and large-scale studies remain low in number in this developing area.We therefore aim to present a summary and review of the available published data in this area to help us better understand the emerging role of DBT in IBD.

Quality Safety Standards of Organic Mango

This article conducts a brief analysis of the factors that affect the quality safety of organic mango, and discusses the organic production measures for improving the quality and quality safety of mango, including the choice of environment of place of origin, varieties and seedlings, fertilizers and fertilization, plant protection products and other production inputs. A test is carried out in 0.667 hm2 of base in Tianyang County, Baise City. Content of lead, arsenic and 14 kinds of pesticide residue such as BHC in the mango are not detected; the content of heavy metal such as mercury and cadmium is 0.001-0.006 mg/kg. Then the quality and quality safety indicators of organic mango are discussed, and finally the Guangxi local standards of organic mango products are developed.

Simulation About the Growth of Chinese Firm's Safety Management Capability

Aiming at the deficiency of exterminating measures of Chinese firm safety management, a simulation model of Chinese firm＇s safety management capability based on the organizational learning theory, in which the simulation method of system dynamics is utilized. The level variable and rate variable are designed based on the practical situation and change situation of corresponding variables of firm＇s safety management ca- pability. Simulation firms are built with accident case groups of the oil industry, chemical industry, machine industry, coal mining industry, and weapon industry. Through analyzing the simulation result, the growth law of Chinese firm＇s safety management capability is obtained as follows： the accumulating and the coupling of safety knowledge should be emphasized at the same time; the balance of learning behavior of individual, group and organization should be considered together; different types of Chinese firm should take different safety policies according to their practical situations.

Safety and Tolerability of Transdermal Rotigotine in a Clinical Practice Cohort for 2 Years

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disease that occurs as a result of loss of dopaminergic neurons from the substantia nigra. Rotigotine is a non-ergolinic dopamine agonist available as a silicone-based transdermal patch for the treatment of PD. In the European Union, rotigotine transdermal patch is indicated for use as monotherapy in early idiopathic PD, or in combination with levodopa through the disease course to the late stages where motor complications with levodopa become an issue. Objective: To investigate the safety and tolerability of transdermal rotigotine, in patients with PD being treated during routine clinical practice for 2 years. Results: 114 patients were enrolled, and evaluated for adverse events over a 24-month period. Adverse events occurred in 39 patients (34.21%). 23 patients (20.17%) reported application site reactions (dermatitis, erythema, itching), and 16 (14.03%) had systemic adverse events. Sleep disorders were the most common problem;the others were hallucinations, depression, dizziness, and syncope. No patient experienced dyskinesia. Adverse events necessitated the discontinuation of rotigotine for application site reactions in fourteen patients (12.28%) and 11 patients (9.64%);reasons for discontinuation were systemic adverse events. Conclusion: Rotigotine is safe and well tolerated when used to treat PD in routine clinical practice.

Simulation modeling on the growth of firm's safety management capability

Aiming to the deficiency of safety management measure,established simulation model about firm's safety management capability(FSMC) based on organizational learning theory.The system dynamics(SD) method was used,in which level and rate system,vari- able equation and system structure flow diagram was concluded.Simulation model was verified from two aspects: first,model's sensitivity to variable was tested from the gross of safety investment and the proportion of safety investment;second,variables dependency was checked up from the correlative variable of FSMC and organizational learning.The feasibility of simulation model is verified though these processes.