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Is in vivo sensing in a total hip replacement a possibility? A review on past systems and future challenges 全髋关节置换术中的体内传感是可能的吗?回顾过去的制度和未来的挑战
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2021-01-01 DOI: 10.1088/2516-1091/ac1b7f
O. Vickers, P. Culmer, G. Isaac, R. Kay, M. P. Shuttleworth, T. Board, S. Williams
Surgery to implant a total hip replacement (THR) is very successful in reducing pain and restoring function. This procedure has become more prevalent, and projections estimate further increases in demand. However, complications can arise, and current diagnostic techniques often fail to expose underlying issues before they result in a catastrophic failure that requires revision surgery. An instrumented implant, with embedded sensors capable of real time condition monitoring, would be an attractive proposition to incorporate within a THR. Continued advances in the performance and miniaturisation of electronic components, embedded systems, sensing and wireless communications have given the tools and resources medical device manufacturers need to innovate in the field of implantable medical devices. Smart implants are already being widely used in healthcare including pacemakers, cochlear implants, glucose monitors and insulin pumps however, a widely used smart THR has not yet been realised. Since the implantation of the first instrumented hip implant in the 1960s there have been several in vitro studies monitoring levels of implant loosening. Additionally, significant research has been conducted using instrumented THRs to perform in vivo measurement of biomechanical metrics, including force and moments. To date less than 100 patients have successfully received an instrumented implant. The results of these studies have aided researchers, designers and surgeons in wider research projects, however, the motivation behind the work was to provide discrete biomechanical data sets and not provide real-time condition monitoring of an implants performance or highlight early indications for revision surgery. If in vivo sensing within a THR is to be achieved and adopted in regular clinical practice then the following challenges need to be addressed: choice of the sensing method, biocompatibility and integration within the implant, power supply, communication, and regulatory considerations.
手术植入全髋关节置换术(THR)在减轻疼痛和恢复功能方面非常成功。这一程序已变得更加普遍,预计需求将进一步增加。然而,并发症可能会出现,目前的诊断技术往往不能在导致需要翻修手术的灾难性失败之前暴露潜在的问题。一种带有嵌入式传感器的仪器植入物,能够实时监测状态,将是一个有吸引力的提议,纳入THR。电子元件、嵌入式系统、传感和无线通信的性能和小型化的持续进步,为医疗设备制造商提供了在植入式医疗设备领域进行创新所需的工具和资源。智能植入物已经广泛应用于医疗保健领域,包括起搏器、耳蜗植入物、血糖监测仪和胰岛素泵,然而,广泛使用的智能THR尚未实现。自20世纪60年代首次植入人工髋关节以来,已经进行了几项体外研究,监测人工髋关节松动的水平。此外,已经进行了大量研究,使用仪器化的THRs进行生物力学指标的体内测量,包括力和力矩。迄今为止,只有不到100名患者成功接受了器械植入。这些研究的结果在更广泛的研究项目中为研究人员、设计师和外科医生提供了帮助,然而,这项工作背后的动机是提供离散的生物力学数据集,而不是提供植入物性能的实时状态监测或突出修复手术的早期适应症。如果要在THR内实现体内传感并在常规临床实践中采用,则需要解决以下挑战:传感方法的选择、植入物内的生物相容性和整合、电源、通信和监管考虑。
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引用次数: 2
Deep learning in medical image registration 医学图像配准中的深度学习
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2020-12-14 DOI: 10.1088/2516-1091/abd37c
Xiang Chen, A. Diaz-Pinto, N. Ravikumar, Alejandro F Frangi
Image registration is a fundamental task in multiple medical image analysis applications. With the advent of deep learning, there have been significant advances in algorithmic performance for various computer vision tasks in recent years, including medical image registration. The last couple of years have seen a dramatic increase in the development of deep learning-based medical image registration algorithms. Consequently, a comprehensive review of the current state-of-the-art algorithms in the field is timely, and necessary. This review is aimed at understanding the clinical applications and challenges that drove this innovation, analysing the functionality and limitations of existing approaches, and at providing insights to open challenges and as yet unmet clinical needs that could shape future research directions. To this end, the main contributions of this paper are: (a) discussion of all deep learning-based medical image registration papers published since 2013 with significant methodological and/or functional contributions to the field; (b) analysis of the development and evolution of deep learning-based image registration methods, summarising the current trends and challenges in the domain; and (c) overview of unmet clinical needs and potential directions for future research in deep learning-based medical image registration.
图像配准是多种医学图像分析应用中的一项基本任务。随着深度学习的出现,近年来各种计算机视觉任务的算法性能取得了重大进展,包括医学图像配准。在过去的几年里,基于深度学习的医学图像配准算法的发展有了显著的增长。因此,对该领域当前最先进的算法进行全面审查是及时的,也是必要的。本综述旨在了解推动这一创新的临床应用和挑战,分析现有方法的功能和局限性,并为开放的挑战和尚未满足的临床需求提供见解,这些挑战和需求可能会影响未来的研究方向。为此,本文的主要贡献是:(a)讨论了自2013年以来发表的所有基于深度学习的医学图像配准论文,这些论文在方法和/或功能上对该领域有重大贡献;(b)分析了基于深度学习的图像配准方法的发展和演变,总结了该领域当前的趋势和挑战;(c)基于深度学习的医学图像配准未满足的临床需求和未来研究的潜在方向。
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引用次数: 57
Hydrogel biomaterials to support and guide vascularization 水凝胶生物材料支持和引导血管形成
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2020-11-10 DOI: 10.1088/2516-1091/abc947
R. Chapla, J. West
Biomaterials can be intentionally designed to support and even guide vascularization for applications ranging from engineered organs to treatment of ischemic diseases like myocardial infarction and stroke. In order to appropriately design bioactive biomaterials for vascularization, it is important to understand the cellular and molecular events involved in angiogenesis and vasculogenesis. Cell-matrix and signaling biomolecule interactions that initiate and promote formation of vasculature in vivo can often be mimicked in biomaterial platforms. Hydrogels are frequently used in these applications because they are soft and hydrated with mechanical properties similar to soft tissues and because many synthetic hydrogels are essentially bioinert, allowing one to engineer in specific cell-material interactions. A variety of both naturally-derived and synthetic hydrogel bases are used for supporting vascularization, and these gels are tailored to possess mechanical properties, biodegradation, cell adhesive interactions, biochemical signaling, and/or architectural properties that can promote assembly and tubulogenesis by vascular cells. This article serves to review current hydrogel materials and the innovative design modifications implemented to guide and support the vascularization process.
生物材料可以有意设计用于支持甚至指导血管形成,应用范围从工程器官到心肌梗死和中风等缺血性疾病的治疗。为了适当地设计用于血管生成的生物活性生物材料,了解血管生成和血管生成中涉及的细胞和分子事件是重要的。启动和促进体内血管系统形成的细胞-基质和信号传导生物分子相互作用通常可以在生物材料平台中模拟。水凝胶经常用于这些应用,因为它们柔软且水合,具有类似于软组织的机械性能,并且因为许多合成水凝胶基本上是生物惰性的,允许人们在特定的细胞-材料相互作用中进行工程。各种天然和合成的水凝胶基质都用于支持血管形成,这些凝胶经过定制,具有机械性能、生物降解、细胞粘附相互作用、生物化学信号和/或结构特性,可以促进血管细胞的组装和管生成。本文综述了目前的水凝胶材料以及为指导和支持血管形成过程而进行的创新设计修改。
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引用次数: 7
Modeling metastasis: engineering approaches to study the metastatic cascade 转移模型:转移级联研究的工程方法
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2020-10-21 DOI: 10.1088/2516-1091/abc34f
Hawley C. Pruitt, S. Gerecht
Tumor progression and metastasis requires a complex interplay between tumor cells and their surrounding environment. Conventional 2D and 3D tissue culture models lack the precision and spatiotemporal control required to accurately model the complexity of the tumor microenvironment and metastatic cascade. Advances in biomedical engineering have allowed us to generate precise and versatile model systems to elucidate mechanisms vital to tumor progression and metastasis. The incorporation of novel biomaterials creates a specific mechanical environment that has facilitated controlled studies of cancer cell mechano-transduction. In addition, microfluidic devices have not only allowed for the incorporation of flow and shear forces into vascularized tumor models, but also elucidated vital mechanisms of cancer cell migration that have shifted paradigms about the mode in which cancer cells initiate metastasis. Here, we review the latest developments in biomedical engineering approaches to model the tumor microenvironment and metastatic cascade. We discuss how these approaches have advanced the field of cancer biology and enhanced our understanding of the mechanisms driving metastasis. We initially focus on physical and mechanical aspects of the primary microenvironment that impact tumor cell invasion. We then transition to tumor cell migration using models of tumor extracellular matrix including confined migration. Finally, we review models of intravasation/extravasation and colonization of secondary sites.
肿瘤的进展和转移需要肿瘤细胞和周围环境之间复杂的相互作用。传统的2D和3D组织培养模型缺乏精确模拟肿瘤微环境和转移级联的复杂性所需的精度和时空控制。生物医学工程的进步使我们能够产生精确和通用的模型系统来阐明肿瘤进展和转移的重要机制。新型生物材料的结合创造了一个特定的机械环境,促进了癌细胞机械转导的受控研究。此外,微流体装置不仅允许将流动和剪切力纳入血管化肿瘤模型,而且还阐明了癌细胞迁移的重要机制,改变了关于癌细胞启动转移模式的范式。在这里,我们回顾了生物医学工程方法模拟肿瘤微环境和转移级联的最新进展。我们讨论了这些方法如何推动了癌症生物学领域的发展,并增强了我们对肿瘤转移机制的理解。我们首先关注影响肿瘤细胞侵袭的初级微环境的物理和机械方面。然后我们使用肿瘤细胞外基质模型过渡到肿瘤细胞迁移,包括有限迁移。最后,我们回顾了内渗/外渗和继发部位定植的模型。
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引用次数: 0
Critical review on where CRISPR meets molecular diagnostics 评述CRISPR与分子诊断的交集
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2020-10-08 DOI: 10.1088/2516-1091/abbf5e
A. Lau, C. Ren, Luke P Lee
Simple yet powerful clustered regularly-interspaced short palindromic repeats (CRISPR) technology has led to the advent of numerous developments in life sciences, biotechnology, therapeutics, and molecular diagnostics, enabled by gene editing capability. By exploiting the CRISPR-Cas system’s nucleic acid sequence detection abilities, CRISPR-based molecular diagnostics have been developed. Here, we review the development of rapid, sensitive, and inexpensive CRISPR-based molecular diagnostics. We introduce the transition of CRISPR technology to precision molecular diagnostic devices from tube to device. Next, we discuss the various nucleic acid (NA) detection methods by CRISPR. We address the importance of significant sample preparation steps for a future sample-to-answer solution, which is lacking in current CRISPR-based molecular diagnostic technology. Lastly, we discuss the extension of CRISPR-based molecular diagnostics to various critical applications. We envision CRISPR technology holds great promise for widespread use in precision NA detection applications after particular technical challenges are overcome.
简单而强大的规则间隔短回文重复序列(CRISPR)技术在基因编辑能力的推动下,在生命科学、生物技术、治疗学和分子诊断学领域取得了许多发展。通过利用CRISPR-Cas系统的核酸序列检测能力,开发了基于CRISPR的分子诊断。在这里,我们回顾了快速、灵敏和廉价的基于CRISPR的分子诊断的发展。我们介绍了CRISPR技术向精密分子诊断设备的转变,从试管到设备。接下来,我们将讨论CRISPR检测核酸(NA)的各种方法。我们讨论了重要的样本制备步骤对未来样本应答解决方案的重要性,这是当前基于CRISPR的分子诊断技术所缺乏的。最后,我们讨论了基于CRISPR的分子诊断技术在各种关键应用中的扩展。我们设想,在克服特定的技术挑战后,CRISPR技术有望在精确NA检测应用中广泛应用。
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引用次数: 17
Fundamentals of the gut for capsule engineers 太空舱工程师的肠道基础知识
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2020-09-25 DOI: 10.1088/2516-1091/abab4c
L. Barducci, J. Norton, Sunandita Sarker, Sayeed Mohammed, Ryan Jones, P. Valdastri, B. Terry
The gastrointestinal (GI) tract is a complex environment comprised of the mouth, esophagus, stomach, small and large intestines, rectum and anus, which all cooperate to form the complete working GI system. Access to the GI using endoscopy has been augmented over the past several decades by swallowable diagnostic electromechanical devices, such as pill cameras. Research continues today and into the foreseeable future on new and more capable miniature devices for the purposes of systemic drug delivery, therapy, tissue biopsy, microbiome sampling, and a host of other novel ground-breaking applications. The purpose of this review is to provide engineers in this field a comprehensive reference manual of the GI environment and its complex physical, biological, and chemical characteristics so they can more quickly understand the constraints and challenges associated with developing devices for the GI space. To accomplish this, the work reviews and summarizes a broad spectrum of literature covering the main anatomical and physiological properties of the GI tract that are pertinent to successful development and operation of an electromechanical device. Each organ in the GI is discussed in this context, including the main mechanisms of digestion, chemical and mechanical processes that could impact devices, and GI motor behavior and resultant forces that may be experienced by objects as they move through the environment of the gut.
胃肠道是一个复杂的环境,由口腔、食道、胃、小肠和大肠、直肠和肛门组成,它们共同合作形成完整的胃肠道系统。在过去的几十年里,通过可吞咽的机电诊断设备,如药丸相机,增加了使用内窥镜检查胃肠道的机会。在可预见的未来,研究人员将继续研究新的、功能更强的微型设备,用于全身药物输送、治疗、组织活检、微生物组采样和许多其他新颖的突破性应用。本综述的目的是为该领域的工程师提供GI环境及其复杂的物理、生物和化学特性的综合参考手册,以便他们能够更快地了解与开发GI空间设备相关的限制和挑战。为了实现这一目标,本研究回顾和总结了广泛的文献,这些文献涵盖了胃肠道的主要解剖和生理特性,这些特性与机电设备的成功开发和操作有关。在此背景下讨论了胃肠道中的每个器官,包括消化的主要机制,可能影响设备的化学和机械过程,以及胃肠道运动行为和物体在肠道环境中移动时可能经历的合力。
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引用次数: 19
The magic bullet as cancer therapeutic—has nanotechnology failed to find its mark? 癌症治疗药物纳米技术的灵丹妙药没有找到它的标记?
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2020-09-24 DOI: 10.1088/2516-1091/abb008
G. Xiong, K. Venkatraman, S. Venkatraman
Ever since the term ‘Magic Bullet’ was coined by Nobel laureate Paul Ehrlich to denote selective activity of a therapeutic medicine against a particular target tissue or organism, researchers have been attempting to develop the concept, with the major part of the work directed towards cancer targets. In this review, we define four major technologies that embody the Magic Bullet concept, and discuss the status of the therapeutic in each case. The reasons for relative success and failure of the four technologies are assessed based on the clinical outcomes. There have been failures of ancillary concepts (to enable selectivity) such as the enhanced permeation and retention effect, which will be discussed in context. The outlook is hopeful, with the advent of immunotherapies, that the idealized Magic Bullet will see the light of day in the near future.
自从诺贝尔奖获得者保罗·埃利希创造了“灵丹妙药”一词来表示治疗药物对特定靶组织或生物体的选择性活性以来,研究人员一直在尝试发展这一概念,其主要工作是针对癌症靶点。在这篇综述中,我们定义了体现魔术子弹概念的四种主要技术,并讨论了每种情况下的治疗现状。根据临床结果评估这四种技术相对成功和失败的原因。辅助概念(实现选择性)已经失败,例如增强的渗透和保留效应,这将在上下文中讨论。随着免疫疗法的出现,人们对理想化的灵丹妙药将在不久的将来重见天日充满希望。
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引用次数: 5
Interdisciplinary approaches to advanced cardiovascular tissue engineering: ECM-based biomaterials, 3D bioprinting, and its assessment 先进心血管组织工程的跨学科方法:基于ecm的生物材料,生物3D打印及其评估
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2020-09-24 DOI: 10.1088/2516-1091/abb211
U. Yong, Sooyeon Lee, Seungman Jung, Jinah Jang
As a class of representative intractable diseases, cardiovascular disease (CVD) is the most common cause of global mortality, accounting for approximately 17.9 million deaths each year. At the end of the disease stage, surgery for replacement of cardiovascular (CV) tissue is inevitably required due to the limited regeneration capacity of CV tissue. However, the currently available methods (e.g. autografts, allografts, xenografts, prostheses) have limited therapeutic efficacy because of donor shortage, immunological transplant rejection, anticoagulant therapy, and less durability. To overcome these limitations, CV tissue engineering technology has been extensively explored to develop replaceable tissue and organs for in vivo transplantation. In addition, 3D tissue models are also studied for in vitro mechanistic study and therapeutic screening. To accomplish this, there has been tremendous progress in studying various CV tissue-specific biomaterials and advanced 3D bioprinting techniques to enhance the physiological and anatomical relevance of engineered CV tissues. Moreover, a variety of evaluation methods have been investigated to validate the unique structural properties and electrical activity of the engineered CV tissues towards non- or less-invasive and real-time assessments in 3D volumetric structures. In this review, we systemically present and discuss the advantages and applications of CV tissue-specific biomaterials, 3D bioprinting techniques, and assessment methods that can facilitate real-time monitoring. A thorough understanding of advanced strategies in CV tissue engineering can be utilized to guide work on next-generation therapeutics for CVD.
心血管疾病作为一类具有代表性的顽固性疾病,是全球最常见的死亡原因,每年约有1790万人死亡。在疾病阶段结束时,由于心血管组织的再生能力有限,不可避免地需要进行心血管(CV)组织置换手术。然而,目前可用的方法(如自体移植物、同种异体移植物、异种移植物、假体)由于供体短缺、免疫移植排斥反应、抗凝治疗和耐久性较差,治疗效果有限。为了克服这些限制,CV组织工程技术已被广泛探索,以开发用于体内移植的可替代组织和器官。此外,3D组织模型也被研究用于体外机制研究和治疗筛选。为了实现这一目标,在研究各种CV组织特异性生物材料和先进的3D生物打印技术以增强工程CV组织的生理和解剖相关性方面取得了巨大进展。此外,已经研究了各种评估方法,以验证工程CV组织的独特结构特性和电活性,从而在三维体积结构中进行无创或微创的实时评估。在这篇综述中,我们系统地介绍和讨论了CV组织特异性生物材料、3D生物打印技术以及有助于实时监测的评估方法的优势和应用。对心血管组织工程先进策略的深入了解可用于指导下一代心血管疾病治疗方法的工作。
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引用次数: 8
Optical spectroscopy for in vivo medical diagnosis—a review of the state of the art and future perspectives 光谱学在体内医学诊断中的应用——技术现状和未来展望综述
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2020-08-26 DOI: 10.1088/2516-1091/abaaa3
J. Kim, D. Wales, Guang‐Zhong Yang
When light is incident to a biological tissue surface, combinations of optical processes occur, such as reflection, absorption, elastic and non-elastic scattering, and fluorescence. Analysis of these light interactions with the tissue provides insight into the metabolic and pathological state of the tissue. Furthermore, in vivo diagnosis of diseases using optical spectroscopy enables in situ rapid clinical decisions without invasive biopsies. For in vivo scenarios, incident light can be delivered in a highly localized manner to tissue via optical fibers, which are placed within the working channels of minimally invasive clinical tools, such as endoscopes. There has been extensive development in the accuracy and specificity of these optical spectroscopy techniques since the earliest in vivo examples were published in the academic literature in the early ‘90s, and there are now commercially available systems that have undergone medical and clinical trials. In this review, several types of optical spectroscopy techniques (elastic optical scattering spectroscopy, fluorescence spectroscopy, Raman spectroscopy, and multimodal spectroscopy) for the diagnosis and monitoring of diseases states of tissue in an in vivo setting are introduced and explored. Examples of the latest and most impactful works for each technique are then critically reviewed. Finally, current challenges and unmet clinical needs are discussed, followed by future opportunities, such as point-based spectroscopies for robot-guided surgical interventions.
当光入射到生物组织表面时,发生光学过程的组合,例如反射、吸收、弹性和非弹性散射以及荧光。对这些光与组织的相互作用的分析提供了对组织代谢和病理状态的深入了解。此外,使用光学光谱对疾病进行体内诊断能够在没有侵入性活检的情况下进行原位快速临床决策。对于体内场景,入射光可以通过光纤以高度局部化的方式传递到组织,光纤放置在微创临床工具(如内窥镜)的工作通道内。自从90年代初最早的体内实例发表在学术文献中以来,这些光谱技术的准确性和特异性已经得到了广泛的发展,现在已经有经过医学和临床试验的商用系统。在这篇综述中,介绍和探索了几种类型的光谱技术(弹性光学散射光谱、荧光光谱、拉曼光谱和多峰光谱),用于在体内环境中诊断和监测组织的疾病状态。然后对每种技术的最新和最具影响力的作品的例子进行批判性的回顾。最后,讨论了当前的挑战和未满足的临床需求,以及未来的机会,如机器人引导手术干预的基于点的光谱学。
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引用次数: 31
Challenges of continuum robots in clinical context: a review 连续体机器人在临床环境中的挑战:综述
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2020-08-03 DOI: 10.1088/2516-1091/ab9f41
Tomás da Veiga, J. Chandler, P. Lloyd, G. Pittiglio, N. J. Wilkinson, A. K. Hoshiar, R. Harris, P. Valdastri
With the maturity of surgical robotic systems based on traditional rigid-link principles, the rate of progress slowed as limits of size and controllable degrees of freedom were reached. Continuum robots came with the potential to deliver a step change in the next generation of medical devices, by providing better access, safer interactions and making new procedures possible. Over the last few years, several continuum robotic systems have been launched commercially and have been increasingly adopted in hospitals. Despite the clear progress achieved, continuum robots still suffer from design complexity hindering their dexterity and scalability. Recent advances in actuation methods have looked to address this issue, offering alternatives to commonly employed approaches. Additionally, continuum structures introduce significant complexity in modelling, sensing, control and fabrication; topics which are of particular focus in the robotics community. It is, therefore, the aim of the presented work to highlight the pertinent areas of active research and to discuss the challenges to be addressed before the potential of continuum robots as medical devices may be fully realised.
随着基于传统刚杆原理的手术机器人系统的成熟,随着尺寸和可控自由度的限制,其发展速度减慢。Continuum机器人通过提供更好的访问、更安全的交互和使新程序成为可能,具有在下一代医疗设备中实现跨越式变化的潜力。在过去的几年里,几个连续体机器人系统已经投入商业应用,并越来越多地应用于医院。尽管取得了明显的进展,连续体机器人仍然受到设计复杂性的影响,阻碍了它们的灵活性和可扩展性。最近在驱动方法方面的进展已经解决了这个问题,为常用的方法提供了替代方案。此外,连续体结构在建模、传感、控制和制造方面引入了显著的复杂性;机器人社区特别关注的主题。因此,本文的目的是强调积极研究的相关领域,并讨论在连续体机器人作为医疗设备的潜力得到充分实现之前需要解决的挑战。
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引用次数: 100
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Progress in biomedical engineering (Bristol, England)
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