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The Role of the IACUC in the Absence of Regulatory Guidance. IACUC在缺乏监管指导的情况下的作用。
IF 2.5 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2019-12-31 DOI: 10.1093/ilar/ilz003
Stuart E Leland, Pamela A Straeter, Beverly Jan Gnadt

Institutional Animal Care and Use Committees (IACUCs) occasionally face regulatory requirements for which clear guidance may not be available. Either the regulating body has chosen not to provide such guidance or the guidance may be minimal or even ambiguous. Such guidance may be desirable when institutions have research needs, in which case IACUCs are left to their own interpretation to develop internal policies, procedures, and documents. Typically, this is approached by an IACUC working with partners in the laboratory animal community and may involve input from regulators who can provide context as well as parameters to consider. Over time, shared institutional experiences and documentation coalesce to create a general framework that provides a baseline for others to consider as templates for further policy elaboration or development. The strength of this approach relies on the ability to share freely, including having unobstructed access to such documents.

机构动物保护和使用委员会(IACUCs)偶尔会面临监管要求,而这些要求可能没有明确的指导。监管机构要么选择不提供这种指导,要么这种指导可能很少,甚至含糊不清。当机构有研究需要时,这种指导可能是可取的,在这种情况下,IACUCs可以自行解释,制定内部政策、程序和文件。通常,这是由IACUC与实验动物界的合作伙伴合作解决的,可能涉及监管机构的投入,他们可以提供背景和参数。随着时间的推移,共同的机构经验和文件形成了一个总的框架,为其他人提供了一个基线,作为进一步制定政策或制定政策的模板。这种方法的优势在于自由分享的能力,包括不受阻碍地访问这些文件。
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引用次数: 4
The Role of IACUCs in Responsible Animal Research. IACUC在负责任动物研究中的作用。
IF 2.5 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2019-11-11 DOI: 10.1093/ilar/ilz016
S. Mohan, R. Huneke
In order to ensure animal welfare during the course of scientific enquiry, there is a strong framework of animal welfare standards for the use of animals in biomedical research [1]. Within the United states much of animal research in the public sector is covered under the Public Health Service Policy on Humane Care and Use of Laboratory Animals (PHS Policy), which is under the provision of the Health Research Extension Act (HREA, 1985) (Public Law 99-158) [2]. The PHS Policy requires that all institutions using live vertebrate animals in PHS supported research must have an institutional animal care and use committee (IACUC) to oversee the care and use of its animals. These institutions are required to use the Guide for the Care and Use of Laboratory Animals (Guide), as a primary standard for implementing their animal care and use programs. Compliance with the Animal Welfare Act Regulations (AWARs) is also an important requirement of the PHS Policy. Per the PHS policy, the IACUC must have at least five members including the chairperson, a veterinarian with direct or delegated program authority, a practicing scientist, a member whose primary concerns are in a nonscientific area, and a member who is not affiliated with the institution other than as a member of the IACUC. The AWAR requirements for IACUC composition are that it consists of at least three members including a veterinarian and a member not affiliated with the institution. In addition to ensuring ethical and humane use of animals, the IACUC, due to its structure and function, is uniquely positioned to contribute to the quality of scientific work performed at an institution [3]. Quality of scientific research output is supported by sound experimental design and strategy, rigorous and comprehensive evaluation criteria, responsible research practices, and adequate oversight and training. Additionally, many of the same factors that affect the quality of animal welfare may also impact the quality of scientific research. It is a well-known fact that healthy animals housed in optimal conditions yield the most reliable data, whereas compromised welfare negatively impacts physiology, immunology, and behavior of animals leading to skewed and misrepresented results [3,4]. Additionally, variables in animal care and health can affect repeatability and reproducibility of experiments, and standardization of practices within an animal care program can help reduce variability [4]. Factors that can be standardized to a certain extent include housing practices (lighting, temperature, food, bedding, noise levels, etc.), genetic background, animal source, and health status (disease status, gut microflora, etc.) [4]. While at an institutional level, responsible research is a broad concept encompassing everything from conflict of interest to reproducibility to data management, the conduct of day-today research practices in a reliable manner is what constitutes responsible research. The central role of IACUCs in
为了确保科学研究过程中的动物福利,在生物医学研究中使用动物有一个强有力的动物福利标准框架[1]。在美国,公共部门的大部分动物研究都涵盖在《实验室动物人道护理和使用公共卫生服务政策》(PHS政策)中,该政策符合《健康研究扩展法》(HREA,1985)(公法99-158)[2]的规定。PHS政策要求,在PHS支持的研究中使用活脊椎动物的所有机构都必须有一个机构动物护理和使用委员会(IACUC)来监督其动物的护理和使用。这些机构必须使用《实验动物护理和使用指南》(指南),作为实施其动物护理和利用计划的主要标准。遵守《动物福利法条例》也是PHS政策的一项重要要求。根据PHS政策,IACUC必须至少有五名成员,包括主席、一名具有直接或授权项目权限的兽医、一名执业科学家、一名主要关注非科学领域的成员,以及一名除IACUC成员外与该机构无关的成员。AWAR对IACUC组成的要求是,它至少由三名成员组成,包括一名兽医和一名不隶属于该机构的成员。除了确保动物的伦理和人道使用外,IACUC由于其结构和功能,在提高机构科学工作质量方面具有独特的地位[3]。科学研究成果的质量得到了健全的实验设计和策略、严格和全面的评估标准、负责任的研究实践以及充分的监督和培训的支持。此外,许多影响动物福利质量的因素也可能影响科学研究的质量。众所周知,在最佳条件下饲养的健康动物会产生最可靠的数据,而福利受损会对动物的生理、免疫学和行为产生负面影响,导致结果失真[3,4]。此外,动物护理和健康中的变量会影响实验的可重复性和再现性,动物护理计划中实践的标准化有助于减少可变性[4]。可以在一定程度上标准化的因素包括住房实践(照明、温度、食物、床上用品、噪音水平等)、遗传背景、动物来源和健康状况(疾病状况、肠道菌群等)[4]。虽然在机构层面上,负责任的研究是一个广泛的概念,涵盖了从利益冲突到再现性再到数据管理的方方面面,但以可靠的方式进行当今的研究实践才是负责任研究的组成部分。IACUC在研究动物使用和监督方面的核心作用有助于通过确保动物研究中的道德、科学、标准化做法来保障负责任的动物研究。IACUC在负责任的动物研究中的各种作用如下图所示(图1),并将在本综述中进一步讨论。
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引用次数: 17
Incorporating Laboratory Animal Science into Responsible Biomedical Research. 将实验动物科学纳入负责任的生物医学研究。
IF 2.5 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2019-11-11 DOI: 10.1093/ilar/ilz017
R. Barbee, P. Turner
Biomedical research has made great strides in the past century leading to rapid advances in human life expectancy, all derived from improved understanding, prevention, and treatment of many diseases and conditions. Research involving laboratory animals has played a significant role in this medical progress. However, there continues to be controversy surrounding the use of animals in research, and animal models have been questioned regarding their relevance to human conditions. While research fraud and questionable research practices could potentially contribute to this problem, we argue that a relative ignorance of laboratory animal science has contributed to the "uncontrolled vivarium experiment" that runs parallel to the more controlled scientific experiment. Several variables are discussed, including husbandry, animal environment, social housing, and more, that can contribute to this uncontrolled experiment, and that can simultaneously decrease quality of life for rodent test subjects when ignored. An argument is put forward that laboratory animal veterinarians and scientists can and should play an important role in better controlling such variables. Similarly, the laboratory animal veterinarian and scientist should play an important role in responsible science by addressing complex interdisciplinary challenges.
生物医学研究在过去的一个世纪里取得了长足的进步,导致人类预期寿命的快速提高,这一切都源于对许多疾病和条件的理解、预防和治疗的提高。涉及实验动物的研究在这一医学进步中发挥了重要作用。然而,在研究中使用动物仍然存在争议,动物模型与人类条件的相关性也受到质疑。虽然研究欺诈和可疑的研究实践可能会导致这一问题,但我们认为,对实验室动物科学的相对无知导致了“不受控制的间日动物实验”,该实验与更受控制的科学实验平行。讨论了几个变量,包括畜牧业、动物环境、社会住房等,这些变量可能会导致这一不受控制的实验,并且在被忽视的情况下,会同时降低啮齿动物测试对象的生活质量。有人认为,实验室动物兽医和科学家能够而且应该在更好地控制这些变量方面发挥重要作用。同样,实验室动物兽医和科学家应该通过应对复杂的跨学科挑战,在负责任的科学中发挥重要作用。
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引用次数: 17
The Pursuit and Advancement of Knowledge as a Justification for the Use of Animals in Research. 对知识的追求和进步作为在研究中使用动物的正当理由。
IF 2.5 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2019-10-14 DOI: 10.1093/ilar/ilz013
J. Tannenbaum
It is commonly said that animal research is sometimes ethically appropriate because it can lead to knowledge, irrespective of benefits this knowledge might bring to humans or animals. Proponents of this view, which I call the "knowledge justification," have been unclear about what they mean by the term "knowledge." They also omit from the justification other features of animal research that are intimately connected with the pursuit and advancement of knowledge. This article identifies and includes in a modified knowledge justification 5 general elements of the pursuit and advancement of knowledge in animal research: "knowledge" in the sense of facts, information, or explanations; "knowledge" in the sense of the experience of having knowledge; contemplation; the exercise of intellectual faculties and skills; and pleasures, frustrations, and challenges in the pursuit and advancement of knowledge. The article explains why these elements are valuable and must be given weight in assessing the ethical appropriateness of curiosity-driven animal research. The discussion critiques defenses and applications of current expressions of the knowledge justification. The article offers a preliminary defense of curiosity-driven animal research by arguing that using animals to obtain scientific knowledge and the pleasures of scientific inquiry can be far more valuable for humans and no more harmful to some animals than the use of these animals to produce meat for human consumption. The article presents 2 examples of curiosity-driven animal research to further establish the plausibility of the knowledge justification and suggests questions and guidelines for developing the justification.
人们通常说,动物研究有时在伦理上是合适的,因为它可以带来知识,而不管这些知识可能给人类或动物带来什么好处。这种观点的支持者,我称之为“知识辩护”,一直不清楚他们所说的“知识”是什么意思。他们还从辩护中忽略了动物研究与追求和知识进步密切相关的其他特征。本文在修改后的知识论证中确定并包括了动物研究中追求和推进知识的5个一般要素:事实、信息或解释意义上的“知识”;“知识”指的是拥有知识的经验;沉思;智力:对智力和技能的运用;在追求和进步知识的过程中,有快乐、挫折和挑战。这篇文章解释了为什么这些因素是有价值的,并且在评估好奇心驱动的动物研究的伦理适宜性时必须给予重视。讨论批评了当前知识辩护表达的辩护和应用。这篇文章为好奇心驱使的动物研究提供了初步辩护,认为利用动物获得科学知识和科学探索的乐趣对人类来说可能更有价值,对某些动物来说也不会比利用这些动物生产供人类食用的肉更有害。本文提出了两个好奇心驱动的动物研究的例子,以进一步建立知识证明的合理性,并提出了发展证明的问题和指导方针。
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引用次数: 4
Beyond the 3 Rs to a More Comprehensive Framework of Principles for Animal Research Ethics. 超越3R,建立更全面的动物研究伦理原则框架。
IF 2.5 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2019-10-10 DOI: 10.1093/ilar/ilz011
D. DeGrazia, T. Beauchamp
We have produced a framework of general moral principles for animal research ethics in a book, Principles of Animal Research Ethics, which is forthcoming with Oxford University Press in fall 2019. This book includes a detailed statement and defense of our framework along with critical commentaries on our work from seven eminent scholars: Larry Carbone, Frans de Waal, Rebecca Dresser, Joseph Garner, Brian Hare, Margaret Landi, and Julian Savulescu. In the present paper, we explain the motivation for our project and present our framework of principles. The first section explains why a new framework is both needed and timely, on the basis of six important developments in recent decades. The second section challenges assertions of an unbridgeable gulf dividing the animal-research and animal-protection communities on the issue of animal research. It does so, first, by indicating common ground in the core values of social benefit and animal welfare and, then, by presenting and briefly defending our framework: three principles of social benefit and three principles of animal welfare. These six principles, we argue, constitute a more suitable framework than any other that is currently available, including the canonical 3 Rs advanced in 1959 by William M. S. Russell and Rex L. Burch.
我们在《动物研究伦理原则》一书中制定了动物研究伦理的一般道德原则框架,该书将于2019年秋季由牛津大学出版社出版。这本书包括对我们的框架的详细陈述和辩护,以及七位著名学者对我们工作的批评评论:拉里·卡波恩,弗兰斯·德瓦尔,丽贝卡·德莱塞,约瑟夫·加纳,布莱恩·黑尔,玛格丽特·兰蒂和朱利安·萨乌列斯库。在本文中,我们解释了我们项目的动机,并提出了我们的原则框架。第一部分根据近几十年来的六个重要发展,解释了为什么需要一个新的框架,而且是及时的。第二部分挑战了动物研究和动物保护团体在动物研究问题上存在不可逾越鸿沟的说法。首先,它指出了社会效益和动物福利的核心价值的共同点,然后,介绍并简要地捍卫了我们的框架:社会效益三原则和动物福利三原则。我们认为,这六个原则构成了一个比目前可用的任何其他原则都更合适的框架,包括1959年由威廉·m·s·罗素和雷克斯·l·伯奇提出的规范的3r。
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引用次数: 34
Common Challenges in Safety: A Review and Analysis of AAALAC Findings. 安全性的共同挑战:AAALAC研究结果的回顾和分析。
IF 2.5 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2018-12-31 DOI: 10.1093/ilar/ily011
James R Swearengen

The 8th edition of the Guide for the Care and Use of Laboratory Animals (Guide) is clear in its requirement for each institution to establish and maintain an occupational health and safety (OHS) program as an essential part of the overall program of animal care and use. For over 30 years, AAALAC International has utilized a variety of methods to evaluate this component of OHS programs as part of the accreditation process. AAALAC International began collecting data on site visit findings over 20 years ago using the Guide as a template for establishing the categories and subcategories to which findings are assigned. Data from 1656 findings associated with OHS were identified during calendar years 2014 through 2016. This information was used to provide an overview of the most frequently observed OHS findings that occurred during this time span. The 5 categories representing key OHS areas and the combined percentage of both mandatory findings and suggestions for improvement in each category included: workplace risk/safety assessment (37.3%); personnel protection (36.3%); personnel risk assessment (14.4%); hazard containment (9.4%); and medical services (2.6%). Information on the most commonly observed OHS findings and associated trends may be helpful to animal care and use programs when conducting internal reviews of their own OHS programs.

《实验动物护理和使用指南》(第8版)明确要求每个机构建立和维护职业健康和安全(OHS)计划,作为动物护理和使用总体计划的重要组成部分。30多年来,AAALAC国际利用各种方法来评估职业健康安全计划的这一组成部分,作为认证过程的一部分。AAALAC国际在20多年前就开始收集实地考察结果的数据,使用《指南》作为模板,确定分配结果的类别和子类别。从2014年到2016年,从1656项与职业健康安全相关的发现中确定了数据。该信息用于概述在此时间段内发生的最常见的OHS发现。代表职业健康安全关键领域的5个类别,以及每个类别中强制性调查结果和改进建议的综合百分比包括:工作场所风险/安全评估(37.3%);人员保护(36.3%);人员风险评估(14.4%);危害控制(9.4%);医疗服务(2.6%)。最常见的OHS调查结果和相关趋势的信息可能有助于动物护理和使用计划,当他们自己的OHS计划进行内部审查时。
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引用次数: 1
Foreword and Introduction to This Issue on Contemporary Safety Topics in Animal Research. 前言和介绍这期关于当代动物研究安全主题的问题。
IF 2.5 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2018-12-31 DOI: 10.1093/ilar/ilz004
John Bradfield, Esmeralda Meyer, John N Norton

Institutions with animal care and use programs are obligated to provide for the health and well-being of the animals, but are equally obligated to provide for safety of individuals associated with the program. The topics in this issue of the ILAR Journal, in association with those within the complimentary issue of the Journal of Applied Biosafety, provide a variety of contemporary occupational health and safety considerations in today's animal research programs. Each article addresses key or emerging occupational health and safety topics in institutional animal care and use programs, where the status of the topic, contemporary challenges, and future directions are provided.

有动物护理和使用计划的机构有义务提供动物的健康和福祉,但同样有义务提供与该计划有关的个人的安全。本期ILAR杂志的主题,与《应用生物安全杂志》的免费主题相结合,提供了当今动物研究项目中各种当代职业健康和安全考虑因素。每篇文章都介绍了机构动物护理和使用计划中关键的或新兴的职业健康和安全主题,其中提供了主题的现状,当前的挑战和未来的方向。
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引用次数: 0
Animal Models for Preclinical Development of Allogeneic Hematopoietic Cell Transplantation. 异基因造血细胞移植临床前发展的动物模型。
IF 2.5 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2018-12-31 DOI: 10.1093/ilar/ily006
Scott S Graves, Maura H Parker, Rainer Storb

Since its inception in the 1950s, hematopoietic cell transplantation (HCT) has become a highly effective clinical treatment for malignant and nonmalignant hematological disorders. This milestone in cancer therapy was only possible through decades of intensive research using murine and canine animal models that overcame what appeared in the early days to be insurmountable obstacles. Conditioning protocols for tumor ablation and immunosuppression of the recipient using irradiation and chemotherapeutic drugs were developed in mouse and dog models as well as postgrafting immunosuppression methods essential for dependable donor cell engraftment. The random-bred canine was particularly important in defining the role of histocompatibility barriers and the development of the nonmyeloablative transplantation procedure, making HCT available to elderly patients with comorbidities. Two complications limit the success of HCT: disease relapse and graft versus host disease. Studies in both mice and dogs have made significant progress toward reducing and to some degree eliminating patient morbidity and mortality associated with both disease relapse and graft versus host disease. However, more investigation is needed to make HCT more effective, safer, and available as a treatment modality for other non-life-threatening diseases such as autoimmune disorders. Here, we focus our review on the contributions made by both the murine and canine models for the successful past and future development of HCT.

自20世纪50年代成立以来,造血细胞移植(HCT)已成为治疗恶性和非恶性血液病的高效临床治疗方法。癌症治疗的这一里程碑只有通过几十年的深入研究才有可能实现,这些研究使用了鼠和犬动物模型,克服了早期出现的难以克服的障碍。在小鼠和狗模型中开发了使用放射和化疗药物对受体进行肿瘤消融和免疫抑制的条件治疗方案,以及对可靠的供体细胞移植至关重要的移植后免疫抑制方法。随机培育的犬类在确定组织相容性障碍的作用和非清髓移植程序的发展方面尤为重要,使HCT可用于患有合并症的老年患者。两种并发症限制了HCT的成功:疾病复发和移植物抗宿主疾病。对小鼠和狗的研究在降低并在一定程度上消除与疾病复发和移植物抗宿主病相关的患者发病率和死亡率方面取得了重大进展。然而,还需要更多的研究,以使HCT更有效、更安全,并可作为其他非生命威胁疾病(如自身免疫性疾病)的治疗方式。在这里,我们重点回顾了小鼠和犬模型对HCT过去和未来成功发展的贡献。
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引用次数: 8
Nontraditional Laboratory Animal Species (Cephalopods, Fish, Amphibians, Reptiles, and Birds). 非传统实验动物种类(头足类、鱼类、两栖类、爬行类和鸟类)。
IF 2.5 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2018-12-31 DOI: 10.1093/ilar/ily003
Dorcas P O'Rourke, Cecile L Baccanale, Michael K Stoskopf

Aquatic vertebrates and cephalopods, amphibians, reptiles, and birds offer unique safety and occupational health challenges for laboratory animal personnel. This paper discusses environmental, handling, and zoonotic concerns associated with these species.

水生脊椎动物和头足类动物、两栖动物、爬行动物和鸟类为实验动物人员提供了独特的安全和职业健康挑战。本文讨论了与这些物种有关的环境、处理和人畜共患问题。
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引用次数: 2
Of Mice, Dogs, Pigs, and Men: Choosing the Appropriate Model for Immuno-Oncology Research. 小鼠、狗、猪和人:选择合适的免疫肿瘤研究模型。
IF 2.5 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2018-12-31 DOI: 10.1093/ilar/ily014
Nana H Overgaard, Timothy M Fan, Kyle M Schachtschneider, Daniel R Principe, Lawrence B Schook, Gregers Jungersen

The immune system plays dual roles in response to cancer. The host immune system protects against tumor formation via immunosurveillance; however, recognition of the tumor by immune cells also induces sculpting mechanisms leading to a Darwinian selection of tumor cell variants with reduced immunogenicity. Cancer immunoediting is the concept used to describe the complex interplay between tumor cells and the immune system. This concept, commonly referred to as the three E's, is encompassed by 3 distinct phases of elimination, equilibrium, and escape. Despite impressive results in the clinic, cancer immunotherapy still has room for improvement as many patients remain unresponsive to therapy. Moreover, many of the preclinical results obtained in the widely used mouse models of cancer are lost in translation to human patients. To improve the success rate of immuno-oncology research and preclinical testing of immune-based anticancer therapies, using alternative animal models more closely related to humans is a promising approach. Here, we describe 2 of the major alternative model systems: canine (spontaneous) and porcine (experimental) cancer models. Although dogs display a high rate of spontaneous tumor formation, an increased number of genetically modified porcine models exist. We suggest that the optimal immuno-oncology model may depend on the stage of cancer immunoediting in question. In particular, the spontaneous canine tumor models provide a unique platform for evaluating therapies aimed at the escape phase of cancer, while genetically engineered swine allow for elucidation of tumor-immune cell interactions especially during the phases of elimination and equilibrium.

免疫系统在对癌症的反应中扮演双重角色。宿主免疫系统通过免疫监视来防止肿瘤的形成;然而,免疫细胞对肿瘤的识别也诱导了雕刻机制,导致免疫原性降低的肿瘤细胞变异的达尔文选择。癌症免疫编辑是用来描述肿瘤细胞和免疫系统之间复杂相互作用的概念。这个概念通常被称为三个E,包含了三个不同的阶段:消除、平衡和逃逸。尽管在临床取得了令人印象深刻的成果,但癌症免疫疗法仍有改进的空间,因为许多患者对治疗仍然没有反应。此外,在广泛使用的癌症小鼠模型中获得的许多临床前结果在转化为人类患者时丢失了。为了提高免疫肿瘤学研究和基于免疫的抗癌疗法的临床前测试的成功率,使用与人类更密切相关的替代动物模型是一种很有前途的方法。在这里,我们描述了两种主要的替代模型系统:犬(自发)和猪(实验)癌症模型。虽然狗的自发性肿瘤形成率很高,但转基因猪模型的数量有所增加。我们认为,最佳的免疫肿瘤学模型可能取决于所讨论的癌症免疫编辑的阶段。特别是,自发犬肿瘤模型为评估针对癌症逃逸阶段的治疗提供了一个独特的平台,而基因工程猪允许阐明肿瘤-免疫细胞相互作用,特别是在消除和平衡阶段。
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引用次数: 37
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