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Deterministic models of inhalational anthrax in New Zealand white rabbits. 新西兰白兔吸入性炭疽的确定性模型。
Pub Date : 2014-01-01 Epub Date: 2014-02-14 DOI: 10.1089/bsp.2013.0067
Bradford Gutting

Computational models describing bacterial kinetics were developed for inhalational anthrax in New Zealand white (NZW) rabbits following inhalation of Ames strain B. anthracis. The data used to parameterize the models included bacterial numbers in the airways, lung tissue, draining lymph nodes, and blood. Initial bacterial numbers were deposited spore dose. The first model was a single exponential ordinary differential equation (ODE) with 3 rate parameters that described mucociliated (physical) clearance, immune clearance (bacterial killing), and bacterial growth. At 36 hours postexposure, the ODE model predicted 1.7×10⁷ bacteria in the rabbit, which agreed well with data from actual experiments (4.0×10⁷ bacteria at 36 hours). Next, building on the single ODE model, a physiological-based biokinetic (PBBK) compartmentalized model was developed in which 1 physiological compartment was the lumen of the airways and the other was the rabbit body (lung tissue, lymph nodes, blood). The 2 compartments were connected with a parameter describing transport of bacteria from the airways into the body. The PBBK model predicted 4.9×10⁷ bacteria in the body at 36 hours, and by 45 hours the model showed all clearance mechanisms were saturated, suggesting the rabbit would quickly succumb to the infection. As with the ODE model, the PBBK model results agreed well with laboratory observations. These data are discussed along with the need for and potential application of the models in risk assessment, drug development, and as a general aid to the experimentalist studying inhalational anthrax.

针对新西兰白(NZW)兔吸入艾姆斯菌株炭疽杆菌后的吸入性炭疽建立了描述细菌动力学的计算模型。用于模型参数化的数据包括呼吸道、肺组织、引流淋巴结和血液中的细菌数量。初始细菌数量是孢子剂量的沉积。第一个模型是单指数常微分方程(ODE),有 3 个速率参数,分别描述粘膜(物理)清除、免疫清除(细菌杀灭)和细菌生长。暴露后 36 小时,ODE 模型预测兔子体内的细菌数量为 1.7×10⁷,这与实际实验数据(36 小时内细菌数量为 4.0×10⁷)完全吻合。接下来,在单一 ODE 模型的基础上,建立了一个基于生理的生物动力学(PBBK)分区模型,其中一个生理分区是气道管腔,另一个是兔子身体(肺组织、淋巴结、血液)。这两个区间通过一个描述细菌从呼吸道进入体内的运输参数连接起来。PBBK 模型预测,36 小时后兔子体内的细菌数量为 4.9×10⁷,45 小时后模型显示所有清除机制都已饱和,这表明兔子很快就会被感染。与 ODE 模型一样,PBBK 模型的结果与实验室观察结果非常吻合。本文讨论了这些数据,以及这些模型在风险评估、药物开发和作为研究吸入性炭疽的实验人员的一般辅助工具方面的必要性和潜在应用。
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引用次数: 0
BSL-3 laboratory practices in the United States: comparison of select agent and non-select agent facilities. 美国BSL-3实验室实践:精选剂和非精选剂设施的比较。
Pub Date : 2014-01-01 DOI: 10.1089/bsp.2013.0060
Stephanie L Richards, Victoria C Pompei, Alice Anderson

New construction of biosafety level 3 (BSL-3) laboratories in the United States has increased in the past decade to facilitate research on potential bioterrorism agents. The Centers for Disease Control and Prevention inspect BSL-3 facilities and review commissioning documentation, but no single agency has oversight over all BSL-3 facilities. This article explores the extent to which standard operating procedures in US BSL-3 facilities vary between laboratories with select agent or non-select agent status. Comparisons are made for the following variables: personnel training, decontamination, personal protective equipment (PPE), medical surveillance, security access, laboratory structure and maintenance, funding, and pest management. Facilities working with select agents had more complex training programs and decontamination procedures than non-select agent facilities. Personnel working in select agent laboratories were likely to use powered air purifying respirators, while non-select agent laboratories primarily used N95 respirators. More rigorous medical surveillance was carried out in select agent workers (although not required by the select agent program) and a higher level of restrictive access to laboratories was found. Most select agent and non-select agent laboratories reported adequate structural integrity in facilities; however, differences were observed in personnel perception of funding for repairs. Pest management was carried out by select agent personnel more frequently than non-select agent personnel. Our findings support the need to promote high quality biosafety training and standard operating procedures in both select agent and non-select agent laboratories to improve occupational health and safety.

在过去十年中,美国新建的生物安全3级(BSL-3)实验室有所增加,以促进潜在生物恐怖主义制剂的研究。疾病控制和预防中心检查BSL-3设施并审查调试文件,但没有一个机构对所有BSL-3设施进行监督。本文探讨了在何种程度上标准操作程序在美国BSL-3设施之间的实验室与选择剂或非选择剂状态的差异。对以下变量进行了比较:人员培训、去污、个人防护装备、医疗监测、安全通道、实验室结构和维护、资金和病虫害管理。与非精选代理机构相比,与精选代理机构合作的设施有更复杂的培训计划和净化程序。在精选试剂实验室工作的人员可能使用动力空气净化呼吸器,而非精选试剂实验室主要使用N95呼吸器。对特选特工工作人员进行了更严格的医疗监测(尽管特选特工方案没有要求),并发现进入实验室的限制程度更高。大多数选择剂和非选择剂实验室报告了设施的结构完整性;然而,在人员对维修经费的看法上存在差异。虫害防治由精选药剂人员比非精选药剂人员进行的频率更高。我们的研究结果支持在选择性制剂和非选择性制剂实验室中促进高质量生物安全培训和标准操作程序的必要性,以改善职业健康和安全。
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引用次数: 15
Facilitating access to antiviral medications and information during an influenza pandemic: engaging with the public on possible new strategies. 在流感大流行期间促进获得抗病毒药物和信息:就可能的新战略与公众接触。
Pub Date : 2014-01-01 DOI: 10.1089/bsp.2013.0058
Barbara A Fain, Lisa M Koonin, Michael A Stoto, Umair A Shah, Susan R Cooper, Rachael N Piltch-Loeb, Arthur L Kellermann

Antiviral medications can decrease the severity and duration of influenza, but they are most effective if started within 48 hours of the onset of symptoms. In a severe influenza pandemic, normal channels of obtaining prescriptions and medications could become overwhelmed. To assess public perception of the acceptability and feasibility of alternative strategies for prescribing, distributing, and dispensing antivirals and disseminating information about influenza and its treatment, the Institute of Medicine, with technical assistance from the Centers for Disease Control and Prevention (CDC), convened public engagement events in 3 demographically and geographically diverse communities: Fort Benton, MT; Chattanooga, TN; and Los Angeles, CA. Participants were introduced to the issues associated with pandemic influenza and the challenges of ensuring timely public access to information and medications. They then discussed the advantages and disadvantages of 5 alternative strategies currently being considered by the CDC and its partners. Participants at all 3 venues expressed high levels of acceptance for each of the proposed strategies and contributed useful ideas to support their implementation. This article discusses the key findings from these sessions.

抗病毒药物可以降低流感的严重程度和持续时间,但如果在出现症状后48小时内开始使用,效果最好。在严重的流感大流行中,获得处方和药物的正常渠道可能会不堪重负。为了评估公众对处方、分发和分配抗病毒药物以及传播流感及其治疗信息的替代战略的可接受性和可行性的看法,医学研究所在疾病控制和预防中心(CDC)的技术援助下,在3个人口和地理上不同的社区召集了公众参与活动:马萨诸塞州本顿堡;查塔努加,TN;向与会者介绍了与大流行性流感有关的问题以及确保公众及时获得信息和药物的挑战。然后,他们讨论了疾病预防控制中心及其合作伙伴目前正在考虑的5种备选战略的优缺点。所有三个会场的与会者对每项拟议战略都表示高度接受,并提出了有用的意见,以支持其实施。本文讨论了这些会议的主要发现。
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引用次数: 9
2011 investigation of internal contamination with radioactive strontium following rubidium Rb 82 cardiac PET scan. 2011年铷Rb 82心脏PET扫描后放射性锶内部污染的调查。
Pub Date : 2014-01-01 DOI: 10.1089/bsp.2013.0072
Satish K Pillai, Arthur Chang, Matthew W Murphy, Jennifer Buzzell, Armin Ansari, Robert C Whitcomb, Charles Miller, Robert Jones, David P Saunders, Philip Cavicchia, Sharon M Watkins, Carina Blackmore, John A Williamson, Michael Stephens, Melissa Morrison, James McNees, Rendi Murphree, Martha Buchanan, Anthony Hogan, James Lando, Atmaram Nambiar, Lauren Torso, Joseph M Melnic, Lucie Yang, Lauren Lewis

During routine screening in 2011, US Customs and Border Protection (CBP) identified 2 persons with elevated radioactivity. CBP, in collaboration with Los Alamos National Laboratory, informed the Food and Drug Administration (FDA) that these people could have increased radiation exposure as a result of undergoing cardiac Positron Emission Tomography (PET) scans several months earlier with rubidium Rb 82 chloride injection from CardioGen-82. We conducted a multistate investigation to assess the potential extent and magnitude of radioactive strontium overexposure among patients who had undergone Rb 82 PET scans. We selected a convenience sample of clinical sites in 4 states and reviewed records to identify eligible study participants, defined as people who had had an Rb 82 PET scan between February and July 2011. All participants received direct radiation screening using a radioisotope identifier able to detect the gamma energy specific for strontium-85 (514 keV) and urine bioassay for excreted radioactive strontium. We referred a subset of participants with direct radiation screening counts above background readings for whole body counting (WBC) using a rank ordering of direct radiation screening. The rank order list, from highest to lowest, was used to contact and offer voluntary enrollment for WBC. Of 308 participants, 292 (95%) had direct radiation screening results indistinguishable from background radiation measurements; 261 of 265 (98%) participants with sufficient urine for analysis had radioactive strontium results below minimum detectable activity. None of the 23 participants who underwent WBC demonstrated elevated strontium activity above levels associated with routine use of the rubidium Rb 82 generator. Among investigation participants, we did not identify evidence of strontium internal contamination above permissible levels. This investigation might serve as a model for future investigations of radioactive internal contamination incidents.

在2011年的例行检查中,美国海关及边境保护局(CBP)发现2人的辐射水平升高。美国海关和边境保护局与洛斯阿拉莫斯国家实验室合作,通知美国食品和药物管理局(FDA),这些人可能由于几个月前接受心脏正电子发射断层扫描(PET)扫描,使用CardioGen-82公司的氯化铷Rb 82注射而增加了辐射暴露。我们进行了一项多州调查,以评估在接受Rb 82 PET扫描的患者中放射性锶过度暴露的潜在程度和程度。我们在4个州的临床站点选择了方便的样本,并回顾了记录,以确定符合条件的研究参与者,定义为2011年2月至7月期间进行过Rb 82 PET扫描的人。所有参与者都接受了直接辐射筛查,使用放射性同位素标识符能够检测锶-85 (514 keV)的γ能量特异性,并对排泄的放射性锶进行尿液生物测定。我们将直接辐射筛查计数高于全身计数(WBC)背景读数的参与者分组,使用直接辐射筛查的等级排序。从最高到最低的等级列表用于联系和提供自愿报名WBC。在308名参与者中,292名(95%)的直接辐射筛查结果与背景辐射测量结果无法区分;265名参与者中有261名(98%)有足够的尿液用于分析,其放射性锶结果低于最低可检测活性。接受白细胞计数的23名参与者中,没有人表现出高于常规使用铷Rb 82发生器相关水平的锶活性升高。在调查参与者中,我们没有发现超过允许水平的锶内部污染的证据。这一调查可作为今后放射性内部污染事件调查的一个范本。
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引用次数: 2
Hospital bioterrorism planning and burn surge. 医院生物恐怖袭击计划和烧伤激增。
Pub Date : 2014-01-01 Epub Date: 2014-02-14 DOI: 10.1089/bsp.2013.0065
Randy D Kearns, Brent Myers, Charles B Cairns, Preston B Rich, C Scott Hultman, Anthony G Charles, Samuel W Jones, Grace L Schmits, Mary Beth Skarote, James H Holmes, Bruce A Cairns

On the morning of June 9, 2009, an explosion occurred at a manufacturing plant in Garner, North Carolina. By the end of the day, 68 injured patients had been evaluated at the 3 Level I trauma centers and 3 community hospitals in the Raleigh/Durham metro area (3 people who were buried in the structural collapse died at the scene). Approximately 300 employees were present at the time of the explosion, when natural gas being vented during the repair of a hot water heater ignited. The concussion from the explosion led to structural failure in multiple locations and breached additional natural gas, electrical, and ammonia lines that ran overhead in the 1-story concrete industrial plant. Intent is the major difference between this type of accident and a terrorist using an incendiary device to terrorize a targeted population. But while this disaster lacked intent, the response, rescue, and outcomes were improved as a result of bioterrorism preparedness. This article discusses how bioterrorism hospital preparedness planning, with an all-hazards approach, became the basis for coordinated burn surge disaster preparedness. This real-world disaster challenged a variety of systems, hospitals, and healthcare providers to work efficiently and effectively to manage multiple survivors. Burn-injured patients served as a focus for this work. We describe the response, rescue, and resuscitation provided by first responders and first receivers as well as efforts made to develop burn care capabilities and surge capacity.

2009年6月9日上午,北卡罗来纳州加纳的一家制造工厂发生爆炸。到当天结束时,在罗利/达勒姆都市区的3个一级创伤中心和3个社区医院对68名受伤患者进行了评估(3名被埋在结构倒塌中的人当场死亡)。爆炸发生时,大约有300名员工在场,当时他们正在维修热水器,正在排放的天然气起火。爆炸造成的震荡导致多个地方的结构损坏,并破坏了位于1层混凝土工业厂房上方的额外天然气、电力和氨管道。这种类型的事故与恐怖分子使用燃烧装置恐吓目标人群之间的主要区别在于意图。但是,虽然这次灾难缺乏意图,但由于生物恐怖主义的准备工作,反应、救援和结果都得到了改善。本文讨论了采用全危害方法的生物恐怖主义医院准备计划如何成为协调烧伤激增灾害准备的基础。这场现实世界的灾难对各种系统、医院和医疗保健提供者提出了挑战,要求他们高效地工作,有效地管理多名幸存者。烧伤患者是本研究的重点对象。我们描述了第一响应者和第一接受者提供的反应、救援和复苏,以及为发展烧伤护理能力和激增能力所做的努力。
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引用次数: 9
The influenza vaccine menu. 流感疫苗菜单。
Pub Date : 2013-12-01 Epub Date: 2013-11-20 DOI: 10.1089/bsp.2013.1106
Amesh A Adalja

Medicine for Policymakers is a Journal column that provides decision makers with brief explanations of the meaning and implications for biosecurity of clinical issues. The articles describe, for a nonmedical audience, hospital practices, medical challenges, healthcare delivery issues, and other topics of current interest. Readers may submit ideas to the column's editor, Amesh A. Adalja, MD, through the Journal's editorial office at jjfox@upmc.edu .

决策者的医学是一个杂志专栏,为决策者提供临床问题生物安全的意义和影响的简要解释。这些文章为非医疗读者描述了医院实践、医疗挑战、医疗保健交付问题和其他当前感兴趣的主题。读者可以通过《华尔街日报》编辑部jjfox@upmc.edu向专栏编辑Amesh A. Adalja博士提交想法。
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引用次数: 0
Health security resolutions for 2014. 2014年卫生安全决议。
Pub Date : 2013-12-01 Epub Date: 2013-12-13 DOI: 10.1089/bsp.2013.1309
Anita Cicero, Tom Inglesby
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引用次数: 0
Public health emergencies and responses: what are they, how long do they last, and how many staff does your agency need? 突发公共卫生事件和应对措施:它们是什么,持续多长时间,贵机构需要多少工作人员?
Pub Date : 2013-12-01 Epub Date: 2013-11-12 DOI: 10.1089/bsp.2013.0044
Joseph M Posid, Sherrie M Bruce, Julie T Guarnizo, Ralph C O'Connor, Stephen S Papagiotas, Melissa L Taylor

Responding to outbreaks is one of the most routine yet most important functions of a public health agency. However, some outbreaks are bigger, more visible, or more complex than others, prompting discussion about when an "outbreak" becomes a "public health emergency." When a public health emergency is identified, resources (eg, funding, staff, space) may need to be redirected from core public health programs to contribute to the public health emergency response. The need to sustain critical public health functions while preparing for public health emergency responses raises a series of operational and resource management questions, including when a public health emergency begins and ends, why additional resources are needed, how long an organization should expect staff to be redirected, and how many staff (or what proportion of the agency's staff ) an organization should anticipate will be needed to conduct a public health emergency response. This article addresses these questions from a national perspective by reviewing events for which the Centers for Disease Control and Prevention redirected staff from core public health functions to respond to a series of public health emergencies. We defined "public health emergency" in both operational and public health terms and found that on average each emergency response lasted approximately 4 months and used approximately 9.5% of our workforce. We also provide reasons why public health agencies should consider the impact of redirecting resources when preparing for public health emergencies.

应对疫情是公共卫生机构最常规但最重要的职能之一。然而,一些疫情比其他疫情更大、更明显或更复杂,引发了关于“疫情”何时成为“突发公共卫生事件”的讨论。当确定突发公共卫生事件时,可能需要从核心公共卫生规划中调拨资源(如资金、工作人员、空间),以促进突发公共卫生事件的应对。在准备应对突发公共卫生事件的同时,需要维持关键的公共卫生职能,这就提出了一系列业务和资源管理问题,包括突发公共卫生事件何时开始和结束、为什么需要额外资源、一个组织应预期工作人员需要多长时间才能重新安排工作,以及一个组织应预计将需要多少工作人员(或机构工作人员的比例)来应对突发公共卫生事件。本文通过回顾疾病控制和预防中心将工作人员从核心公共卫生职能部门转移到应对一系列突发公共卫生事件的事件,从国家的角度解决了这些问题。我们从业务和公共卫生两方面定义了“突发公共卫生事件”,发现平均每次突发事件应对持续约4个月,使用了约9.5%的工作人员。我们还提供了公共卫生机构在准备应对突发公共卫生事件时应考虑重新分配资源影响的原因。
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引用次数: 12
Ready or not: analysis of a no-notice mass vaccination field response in Philadelphia. 准备好还是不准备:对费城无通知大规模疫苗接种现场反应的分析。
Pub Date : 2013-12-01 Epub Date: 2013-12-13 DOI: 10.1089/bsp.2013.0064
Jessica Caum, Steven Alles

Local health departments typically rely on exercises to test preparedness capacity; however, pre-scripted drills often lack the sense of urgency that a real event would engender. No-notice, unscripted exercises that challenge staff to think critically under pressure may provide a mechanism for a more realistic assessment of preparedness capacity. The very active influenza season of 2012-13 presented the Public Health Preparedness Program at the Philadelphia Department of Public Health with the opportunity to conduct an influenza vaccination clinic at a local boarding school. Program leaders used this opportunity to design a no-notice exercise to test the ability of staff to effectively coordinate an emergency field response while simultaneously delivering a real public health intervention. On the day of the exercise, staff members were given 6 hours to plan and execute a vaccination clinic without any guidance from program leaders. Best practices observed during the exercise included: (1) early identification and mitigation of rate-limiting steps, and (2) successful implementation of a previously untested high-throughput vaccination model. Although the primary intent of the exercise was to assess the ability of staff to respond to a no-notice event, this vaccination clinic also functioned as a microcosm of a larger response, revealing several considerations related to vaccine ordering, staff resources, and throughput rates that have broader implications for public health responses to large-scale biological attacks or pandemics.

地方卫生部门通常依靠演习来检验防范能力;然而,预先编写的演习往往缺乏真实事件所产生的紧迫感。无通知、无脚本的演习挑战工作人员在压力下进行批判性思考,这可能为更现实地评估备灾能力提供一种机制。2012- 2013年流感季节非常活跃,为费城公共卫生部的公共卫生准备计划提供了在当地寄宿学校开展流感疫苗接种诊所的机会。项目负责人利用这个机会设计了一项不通知演习,以测试工作人员在提供真正的公共卫生干预的同时有效协调紧急情况现场反应的能力。在演习当天,工作人员有6小时的时间来计划和执行一个疫苗接种诊所,没有任何项目负责人的指导。在演习期间观察到的最佳做法包括:(1)早期识别和减缓限速步骤,以及(2)成功实施以前未经测试的高通量疫苗接种模型。虽然演习的主要目的是评估工作人员应对无通知事件的能力,但该疫苗接种诊所也发挥了更大应对措施的一个缩影的作用,揭示了与疫苗订购、工作人员资源和吞吐量有关的若干考虑因素,这些因素对大规模生物袭击或流行病的公共卫生应对具有更广泛的影响。
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引用次数: 10
The meta-leadership summit for preparedness initiative: an innovative model to advance public health preparedness and response. 领导间首脑会议防备倡议:促进公共卫生防备和应对的创新模式。
Pub Date : 2013-12-01 Epub Date: 2013-11-19 DOI: 10.1089/bsp.2013.0056
Robyn K Sobelson, Andrea C Young, Leonard J Marcus, Barry C Dorn, Verla S Neslund, Eric J McNulty

This article reports on the design, evaluation framework, and results from the Meta-Leadership Summit for Preparedness Initiative. The Meta-Leadership Summit for Preparedness was a 5-year initiative based on the premise that national preparedness and emergency response is not solely the responsibility of government. From 2006 to 2011, 36 Meta-Leadership Summits were delivered in communities across the country. Summits were customized, 10-hour leadership development, networking, and community action planning events. They included participation from targeted federal, state, local, nonprofit/philanthropic, and private sector leaders who are directly involved in decision making during a major community or state-wide emergency. A total of 4,971 government, nonprofit, and business leaders attended Meta-Leadership Summits; distribution of attendees by sector was balanced. Ninety-three percent of respondents reported the summit was a valuable use of time, 91% reported the overall quality as "good" or "outstanding," and 91% would recommend the summit to their colleagues. In addition, approximately 6 months after attending a summit, 80% of respondents reported that they had used meta-leadership concepts or principles. Of these, 93% reported that using meta-leadership concepts or principles had made a positive difference for them and their organizations. The Meta-Leadership Summit for Preparedness Initiative was a value-added opportunity for communities, providing the venue for learning the concepts and practice of meta-leadership, multisector collaboration, and resource sharing with the intent of substantively improving preparedness, response, and recovery efforts.

这篇文章报道了设计、评估框架,以及来自预备计划元领导峰会的结果。备灾问题元领导首脑会议是一项为期5年的倡议,其前提是国家备灾和应急反应不仅仅是政府的责任。从2006年到2011年,在全国各地的社区举办了36次元领导力峰会。峰会是定制的,为期10小时的领导力发展、网络和社区行动计划活动。其中包括联邦、州、地方、非营利/慈善机构和私营部门领导人的参与,他们在重大社区或全州紧急情况期间直接参与决策。共有4971位政府、非营利组织和商业领袖参加了元领导力峰会;与会者按行业分布均衡。93%的受访者认为峰会是宝贵的时间利用,91%的受访者认为整体质量“好”或“出色”,91%的受访者会向同事推荐峰会。此外,参加峰会大约6个月后,80%的受访者表示他们使用过元领导概念或原则。其中,93%的人报告说,使用元领导概念或原则对他们和他们的组织产生了积极的影响。预备行动元领导峰会为社区提供了一个增值的机会,为学习元领导、多部门协作和资源共享的概念和实践提供了场所,旨在实质性地改善准备、响应和恢复工作。
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引用次数: 11
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Biosecurity and bioterrorism : biodefense strategy, practice, and science
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