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This review highlights the artificial intelligence, machine learning, and deep learning initiatives supported by the National Institutes of Health (NIH) and the National Eye Institute (NEI) and calls attention to activities and goals defined in the NEI Strategic Plan as well as opportunities for future activities and breakthroughs in ophthalmology.Ophthalmology is at the forefront of artificial intelligence-based innovations in biomedical research that may lead to improvement in early detection and surveillance of ocular disease, prediction of progression, and improved quality of life. Technological advances have ushered in an era where unprecedented amounts of information can be linked that enable scientific discovery. However, there remains an unmet need to collect, harmonize, and share data in a machine actionable manner. Similarly, there is a need to ensure that efforts promote health and research equity by expanding diversity in the data and workforce.The NIH/NEI has supported the development artificial intelligence-based innovations to advance biomedical research. The NIH/NEI has defined activities to achieve these goals in the NIH Strategic Plan for Data Science and the NEI Strategic Plan and have spearheaded initiatives to facilitate research in these areas. more...

19th International Conference in Manufacturing Research ICMR 2022 Manufacturing is a knowledge-intensive business in which companies are distinguished for their ability to deliver products and services using numerous forms of information and knowledge. Various information and communication technologies and systems have been created throughout the years to effectively manage information and knowledge in industry. However, capturing knowledge, particularly tacit knowledge, remains a challenge. Virtual Reality (VR) and Augmented Reality (AR) technologies for industrial tasks have been developed by the research and practitioner communities. For example, in manufacturing, VR/AR have been used to aid in different machining and assembly tasks. This paper presents a proposed an AR equipment ‘Head Mounted Device (HMD)’ under development, as a tool for capturing manufacturing expertise’s knowledge. The technology intends to capture tacit knowledge using a 3D camera installed on the operator's HMD. The proposed approach also supplies the operator with information on production and ongoing processes. The EU Interreg V France Channel England Programme provided funding for this research (CoRoT, Ref: 99). more...

Co-design and co-creation of robotic systems and supporting automated solutions for industrial applications have seen a rapid increase in development efforts in recent years. Research and development activities within collaborative and industrial robotic projects alongside implementations of technical solutions have also shown significant gains in offering small, medium and some large enterprises enough cost benefit justification and improved understanding of technical requirements to adopt them in the ‘servitisation’ of manufacturing and assembly operations. This paper reports findings related to the impact of generating and exchanging technical knowledge within a large multimillion euros project in France-England Channel region over a running duration of over 5 years and the mutual benefits it had on the research institutes, industrial partners and collaborative network established from the project. The results indicated an increase in knowledge acquisition and exchange amongst individuals that can be used to gain significant advantages and a steppingstone in improving new product development activities, speed to market, as well as enhancing methods to establish long term collaborative efforts within industry-academia and improve innovation output. more...

The CoRoT project is a collaboration of French and UK partners funded by the EU Interreg Programme. The CoRoT research group has developed a mobile robot demonstrating autonomous operations particularly aiming for applications within flexible manufacturing factories of small to medium enterprises (SMEs). The robot’s capability of full separation classifies it as a modular robotic system. Although the separation is possible, it introduces challenges in the areas of staff training, physical labour and workshop planning. This paper introduces a new method resolving the overt issues of lifting the robot, storing the robot and making use of the two systems as well as highlighting emergency stop regulations and maintaining the warranty of the equipment. By using a steel framed pneumatic lift, the top module can be removed and held in place, anchoring the arm for full operations whilst freeing the base to perform delivery tasks enabling seamless separation of modular robotic systems. more...

As a concept, Industry 4.0 encompasses the total transformation of the ‘traditional’ production environment with the real-time networking of products, processes and infrastructure via the Internet. What is not clear however, is the functional relationship between pre-existing operational practices such as Lean Manufacturing and Industry 4.0, and thus the associated organisational qualities of ‘Lean-ness’ and ‘Smart-ness’ respectively. This work then presents a formulaic approach to the ubiquitous Lean Manufacturing Value Stream Map process, in order to incorporate Digital elements into traditional product value streams. The result is the creation of a Digital Value Stream Map, which may be utilised to rationalise and deploy Industry 4.0 improvement projects. more...

Monitoring and predicting tool wear is an important issue in dynamic process control under changing conditions, especially for machining large-sized difficult-to-cut materials used in airplanes. Existing tool wear monitoring and prediction methods are mainly based on given cutting conditions over a period of time. This paper presents a novel method for accurately predicting tool wear under varying cutting conditions based on a proposed new meta-learning model which can be easily trained, updated and adapted to new machining tasks of different cutting conditions. Experiments proved a substantial improvement in the accuracy of predicting tool wear compared with existing deep learning methods. more...

Microwave curing technologies have many advantages in manufacturing fiber reinforced polymer composite materials used in aerospace products, compared with traditional autoclave curing technologies. However, the uneven electromagnetic field of microwave in the cavity of the curing chamber results in uneven temperature on the surface of composite laminates during curing, which has been a major obstacle in industrial applications worldwide. Existing methods attempted to solve the problem by the random superposition of uneven electromagnetic fields, but the results were still not satisfactory to meet the high quality requirements of aerospace parts. This paper reveals the one-to-one correspondence between heating patterns of composite parts and microwave curing system settings, and reports a new concept to solve this problem by continuously monitoring and compensating the uneven temperature distribution in real-time. Experimental results from both fiber optical fluorescence sensors and infrared thermal imagers showed significant improvement in temperature uniformity compared with existing methods. more...

Purpose With the customers’ increasing expectation on the product value, manufacturing enterprises around the world have made significant efforts to provide high value-added services in addition to their traditional product development and manufacturing business. For this reason, it is of great importance to research product service system. The purpose of this paper is to research on the key problem of integrated product service system (IPSS) design. Design/methodology/approach A value-oriented IPSS is developed, which is set up based on “requirements-functions-processes-structures” mapping model to give full consideration to customer value and service functions. An extended product-service blueprint, which stems from the service blueprint, is developed to describe product behaviors, service deliver processes, stakeholders’ activities and supporting activities. An ontology-based design support system is proposed to improve design efficiency and help designers making better-informed decisions. A computer-aided prototype system has been developed, and an initial attempt has been made to demonstrate the role of IPSS in the aerospace industry. Findings Many traditional design methods cannot effectively address the objects and processes integration problem of products and services. Moreover, both product and service should be considered in IPSS design, and both of them extremely depend on designers’ own experience and knowledge. Thus, a broader range of knowledge is required to understand product-service system (PSS) design. Research limitations/implications This research provides a solid foundation for PSS C and promotes an effective means for PSS design. Originality/value A customer value-oriented IPSS is presented. Customer requirements are considered during the design phase of PSS as well as both product and service knowledge. more...

Refugees are often exposed to various interrelated stressors including the loss of resources and belongings, death of, or separation from, loved ones as well as direct exposure to armed conflict and violence. Psychological distress is common amongst refugees, with a substantial percentage developing mild to moderate mental disorders such as depression or anxiety disorders. A small percentage of people in refugee settings have severe mental disorders (often exacerbations of pre-existing disorders) and they are especially vulnerable. more...

The increasing market needs and technologies evolution, push companies to develop competitive advantages based on adequate and intensive use of information technology and communication (ICT). However, SMEs do not realize the importance of ICT adoption, which becomes vital for the development, and are not always well equipped to adopt and integrate them to their activities. \ud \ud The paper focused on issues regarding the ICT adoption, especially PLM solutions by SMEs. By analyzing the PLM definitions and works done, we explored indicators that impact positively or negatively ICT and PLM adoption. This paper proposes a model, currently theoretical, with empirical validation proposal through a survey. more...

In an increasingly competitive globalised manufacturing environment, the necessity to develop new products and introduce innovative enhancements to existing ranges has created a critical need for the increased utilisation and sharing of organisational and employee knowledge. The capture of this knowledge within industry is of paramount importance as organisations seek to survive and remain competitive. Crowdsourcing, as a collaborative idea generation and problem solving activity, allows employees to capture explicit knowledge from large groups of colleagues and teams, and offers the potential to extract previously unknown tacit knowledge in a less formal virtual environment. This paper provides a review of recently published literature relating to crowdsourcing in the manufacturing industry and offers suggestions for the future direction of crowdsourcing research in manufacturing and product development. more...

This paper presents a new concept of feature for freeform surface machining that defines the changes in feature status during real manufacturing situations which have not been sufficiently addressed by current international standards and previous research in feature technology. These changes are multi-perspective, including (i) changes in depth-of-cut: the geometry of a feature in the depth-of-cut direction changes during different machining operations such as roughing, semi-finishing and finishing; (ii) changes across the surface: a surface may be divided into different machining regions (effectively sub-features) for the selection of appropriate manufacturing methods for each region such as different cutting tools, parameters, set-ups or machine tools; and (iii) changes in resources or manufacturing capabilities may require the re-planning of depth-of-cuts, division of machining regions and manufacturing operations (machines, tools, set-ups and parameters). Adding the above dynamic information to the part information models in current CAD systems (which only represent the final state of parts) would significantly improve the accuracy, efficiency and timeliness of manufacturing planning and optimisation, especially for the integrated NC machining planning for complex freeform surfaces. A case study in an aircraft manufacturing company will be included in this paper. more...

Product development process deals with large amount of information generated from market survey, concept design, manufacture, test, limited production, production, service, and obsoleting. The information should be stored systematically so that it is easily traceable and reusable for future product development. This paper presents a methodology for seamless product information flow between the three main enterprise information systems such as Computer Aided Design and Manufacturing (CAD/CAM), Product Data/Lifecycle Management (PDM/PLM) and Enterprise Resource Planning (ERP) used in the process of innovative product development while implementing PLM. PLM implementation deals with various existing product data and information generated over years both from CAD and ERP systems. Data integration is very challenging in multi-national engineering companies and has important impact on future decisions while creating new processes. The aim is to define a modular product structure that can be used to connect the product information throughout the life cycle that can be reused effectively and efficiently for future similar products. more...

Purpose – Product-service system (PSS) has been attracting attentions of global manufacturing to providing high-value added services in addition to their traditional product development and manufacturing business. For this reason, it is of great importance to research PSS. The purpose of this paper is to establish a systematic strategy and a system tool for PSS design. Design/methodology/approach – A requirement-driven product-service system (RdPPS) is developed using requirements analysis and knowledge management technologies. A framework is proposed to support RdPPS by providing tools and methods for requirement analysis and processing, formalization of PSS by ontology-based knowledge representation, reasoning method for PSS solution finding, and solution optimizing and assessing. Finally, the design support strategies for RdPPS are investigated to demonstrate the usability and functioning of the developed system. Findings – Many conventional design methods did not consider the influence of customer requirements (CRs) during the planning phase of PSS design. Moreover, a broader range of knowledge is required to PSS design, since both products and services are considered. Research limitations/implications – This research provides a solid foundation for PSS, and promotes an effective means for PSS design. Originality/value – A RdPSS is presented. CRs are considered during the design phase of PSS as well as both product and service knowledge. more...

Providing maintenance and services for high value complex products would extend manufacturers’ responsibilities and benefits to the products’ whole usable life, and provide the opportunities to re-use or re-manufacture some failed parts. Sophisticated Computer Numerical Control (CNC) machine tools in modern manufacturing systems are special products in that they are also used to manufacture other products, and their operation performance directly affects the quality of the manufactured parts as well as the performance of the entire manufacturing system. To ensure CNC machine tools’ consistent performance, appropriate and efficient maintenance and services are essential and this is more challenging as technologies become more sophisticated and the environment is more dynamic. Previous research was mainly focused on maintenance strategy and maintenance scheduling. Very little effort was devoted to providing operational guidance for maintenance process execution, i.e., providing service suppliers with detailed information about resources needed for maintenance such as tooling, consumables, materials and spare parts, as well as service steps including disassembly and assembly of the serviced products. In this project, planning maintenance operation sequences, schedules and resource allocation are the three main tasks for generating final maintenance plans. This paper will present a Collaborative Maintenance Planning System (CoMPS) which will manage information and knowledge to support decision making in maintenance process planning. more...

The guest editors are delighted to present this special issue on Digital Enterprise Technologies in Manufacturing to international researchers and practioners in the manufacturing and related technology and service sectors. The special issue includes carefully selected papers presented at the 9th International Conference on Digital Enterprise Technology held on 29-31 of March 2016 in Nanjing, China. Authors were invited to re-write, extend and significantly improve their papers presented at DET2016. more...

Dynamic Knowledge Management (KM) is a combination of cultural and technological factors, including the cultural factors of people and their motivations, technological factors of content and infrastructure and, where these both come together, interface factors. In this paper a Dynamic KM framework is described in the context of employees being motivated to create profit for their company through product development in high value manufacturing. It is reported how the framework was discussed during a meeting of the collaborating company’s (BAE Systems) project stakeholders. Participants agreed the framework would have most benefit at the start of the product lifecycle before key decisions were made. The framework has been designed to support organisational learning and to reward employees that improve the position of the company in the market place. more...

Manufacturing enterprises around the world have made significant efforts to provide high value added services in addition to their traditional product development and manufacturing business. A product service system (PSS) is presented in this paper which aims to better integrate product development with maintenance and service operations. This project focuses on the maintenance, repair and overhaul (MRO) services in the aerospace industry. A MRO service model is proposed for the development of the proposed PSS. An ontology-based knowledge representation model is developed for the reuse of knowledge unambiguously in MRO services. An initial attempt has been made to demonstrate the role of PSS in the aerospace industry as a decision support tool for MRO services. Product lifecycle management (PLM) environment and Web-based technologies have been developed to enable the methodology to provide services and support in the aerospace manufacturing and flight operations business. more...

This paper presents a new, dynamic feature representation method for high value parts consisting of complex and intersecting features. The method first extracts features from the CAD model of a complex part. Then the dynamic status of each feature is established between various operations to be carried out during the whole manufacturing process. Each manufacturing and verification operation can be planned and optimized using the real conditions of a feature, thus enhancing accuracy, traceability and process control. The dynamic feature representation is complementary to the design models used as underlining basis in current CAD/CAM and decision support systems. more...

The special issue includes carefully selected papers presented at the 9th International Conference on Digital Enterprise Technology (DET2016) which was held on 29-31 March, 2016 in Nanjing, China. Authors were invited to re-write, extend and significantly improve their papers presented at DET2016. The main aim of the conference is to provide an international forum for the exchange of leading edge scientific knowledge and industrial experiences, regarding the development, integration and applications of the various aspects of Digital Enterprise Technologies, in the global manufafturing of the knowledge economy era. more...

Change management is very important to the success of new product development. The earlier that change issues are addressed, the greater that product lifecycle costs can be saved. This paper presents a novel methodology that has been developed to help designers trace, analyse and evaluate engineering changes occurring in the product design phase. A modelling method is employed to enhance the traceability of potential design changes occurring between the functional and structural domains of design. Based on functional and physical models, a matrix is developed to analyse change propagations and help identify design conflicts arising from design changes. A knowledge based methodology has been developed to resolve design conflicts by reusing previous design change knowledge. A wind turbine for power generation from the collaborating company is used to evaluate the developed methodologies. more...

8504Background: Identifying the profile of DNA repair genes predisposing to MM will enable treatment options for patients (pts) and risk assessment for their families. Methods: In this prospective study of the natural history of MM (NCT01950572) we enrolled 239 consecutive pts independent of site of disease, family history of cancer, age at diagnosis, ethnicity, or asbestos exposure. Germline DNA was sequenced for all 239 pts, identifying mutations of all classes in 73 DNA repair genes. Tumor DNA from 12 pts with germline BAP1 mutations was evaluated by whole exome sequencing. Results: Of the 239 pts, 29 (12%) carried a pathogenic germline mutation in a DNA repair gene: BAP1 (N = 17 pts), CHEK2 (N = 5), PALB2 (N = 2), and BRCA2, MLH1, POT1, TP53, and MRE11A (N = 1 each). Pts with mutations were more likely to be female (P = 0.02) and to have been diagnosed with another cancer (P = 0.009). Pts with germline mutations were more likely to have a 1o relative with a diagnosis of MM (P < 0.0001), melanoma (P = ... more...

The manufacturing industry is shifting its emphasis from a traditional supplier of products to a supplier of increasingly integrated products and services, or product-service systems (PSSs). The new paradigm of PSS requires new design methodologies and supporting tools for the effective design and delivery of these enhanced services and integrated PSSs. A case study has been carried out to identify and classify service knowledge applied in practice, both in the service operation and in product design. This paper describes the service issues and service knowledge that has an impact on product design. An initial attempt is made to describe the role of service knowledge in design and also to describe in detail how to apply service knowledge in the conceptual design stage based on an existing requirements management framework modified for this context. This research makes an important contribution to the developing knowledge and information requirements of PSS design. more...

This paper describes a set of modelling guidelines for the improved reuse of manufacturing knowledge in decision support systems. The work draws on research into product and manufacturing knowledge models, and uses a case study based on a simplified jet engine combustion chamber casing to illustrate the proposed guidelines. The paper describes three principles of reuse, i.e., the separation of information from knowledge, the separation of product knowledge from manufacturing process knowledge, and the correct classification of manufacturing knowledge. Whilst the first two principles were found to be well established in the research literature, guidance on how to apply classification hierarchies for optimum reuse was found to be insufficient. The guidelines presented in this paper therefore provide improved guidance on how to classify manufacturing knowledge for optimum reuse. more...

This paper presents novel collaboration methods implemented using a centralized client/server product development integration architecture, and a decentralized peer-to-peer network for smaller and larger companies using open source solutions. The product development integration architecture has been developed for the integration of disparate technologies and software systems for the benefit of collaborative work teams in design and manufacturing. This will facilitate the communication of early design and product development within a distributed and collaborative environment. The novelty of this work is the introduction of an 'out-of-box' concept which provides a standard framework and deploys this utilizing a proprietary state-of-the-art product lifecycle management system (PLM). The term 'out-of-box' means to modify the product development and business processes to suit the technologies rather than vice versa. The key business benefits of adopting such an approach are a rapidly reconfigurable network and minimal requirements for software customization to avoid systems instability. more...

Product knowledge support needs are compared in two companies with different production volumes and product complexity. Knowledge support requirements identified include: function, performance data, requirements data, common parts, regulatory guidelines and layout data. A process based data driven knowledge reuse method is evaluated in light of the identified product knowledge needs. The evaluation takes place through developing a pilot case with each company. It is found that the method provides more benefit to the high complexity design domain, in which a significant amount of work takes place at the conceptual design stages, relying on a conceptual product representation. There is not such a clear value proposition in a design environment whose main challenge is layout design and the application of standard parts and features. The method supports the requirement for conceptual product representation but does not fully support a standard parts library. more...

The problems of collaborative engineering design and knowledge management at the conceptual stage in a network of dissimilar enterprises was investigated. This issue in\ud engineering design is a result of the supply chain and virtual enterprise (VE) oriented industry that demands faster time to market and accurate cost/manufacturing analysis from conception. The solution consisted of a de-centralised super-peer net architecture to establish and maintain communications between enterprises in a VE. In the solution outlined below, the enterprises are able to share knowledge in a common format and nomenclature via the building-block shareable super-ontology that can be tailored on a project by project basis, whilst maintaining the common nomenclature of the ‘super-ontology’ eliminating knowledge interpretation issues. The two-tier architecture layout of the solution glues together the peer-peer and super-ontologies to form a coherent system for both internal and virtual enterprise knowledge management and product development. more...

This paper describes an approach for reusing engineering design knowledge. Many previous design knowledge reuse systems focus exclusively on geometrical data, which is often not applicable in early design stages. The proposed methodology provides an integrated design knowledge reuse framework, bringing together elements of best practice reuse, design rationale capture and knowledge-based support in a single coherent framework. Best practices are reused through the process model. Rationale is supported by product information, which is retrieved through links to design process tasks. Knowledge-based methods are supported by a common design data model, which serves as a single source of design data to support the design process. By using the design process as the basis for knowledge structuring and retrieval, it serves the dual purpose of design process capture and knowledge reuse: capturing and formalising the rationale that underpins the design process, and providing a framework through which design knowledge can be stored, retrieved and applied. The methodology has been tested with an industrial sponsor producing high vacuum pumps for the semiconductor industry. more...

This paper discusses the theoretical aspects and applications of a novel methodology for exploiting a knowledge management editor tool to structure organizational knowledge and integrate it with product development activities. An organizational knowledge framework for capturing and representing manufacturing know-how has been developed using an ontological approach. The captured knowledge is converted into the industry-standard eXtensible mark-up language (XML) and then shared within a web-centric product data management (PDM) system to support a collaborative and distributed product development environment. The key business benefit of adopting such an approach arises from the closer integration between the key technical and business activities taking place during early design. In particular the effectiveness of decision making is increased. more...

Various research studies have concluded that most new design projects are actually re-design activities. This re-design may be for improvement or for reprovision of existing products. Most research efforts for providing computer tools for supporting conceptual or early design mainly concentrated on the design of new products. In practice manufacturing plans generated when an order was placed may quickly become out-dated as the manufacturing environment and constraints often change. It is therefore equally important to regenerate manufacturing plans and re-evaluate design every time a product is changed, re-designed or reordered. This project focuses on manufacturability analysis and provides re-design support for conceptual design of discrete single-piece mechanical parts with emphasis on machined processes. This limitation of implementing the prototype system for re-design activities is not a system design or methodology restriction. The condition has been imposed by the authors as a prelude to validating the system and its results. A novel hybrid approach using a combination of sequential flowchart logic and an expert system has been developed which uses a user-defined feature tree as the input for its analysis. The system allows the designer to estimate manufacturability according to criteria of time and cost, and also to explore different scenarios of parametric variation in the design. A case study has been presented to validate the system’s practicality and usefulness. more...

This paper will describe the development of the web enabled version of a process based engineering design knowledge reuse system. The rationale for using the design process as a central element of knowledge management will be discussed. The system structure will be described. Evaluation of the prototype showed the most valuable attributes of system. Mapping the design process helped to create the product data model. Workshops were used to validate the system. A small number of product parameters are required for developing the product concept in the early stages. The research showed the importance of multi view validation and iteration in system development. It also showed the importance of graphics in design support. Key issues include: the importance of process capture, data model validation, the use of graphics in the interface, system design and system assessment. more...

This paper reports on a collaborative product development and knowledge management platform for Small to Medium Enterprises. It has been recognised that current Product Lifecycle Management (PLM) implementations are document oriented, have a non-customisable data model and inter-enterprise integration difficulties. To overcome these, an ontological knowledge management methodology utilising the semantic web initiative data formats was added to a PLM and an open- source alternative. Shortcomings of centralised architectures are highlighted and a solution using a de-centralised architecture proposed. This is implementable at low cost, the scalability increases in line with user numbers. Ontologies, rules and workflows are reusable and extendable. more...

This paper reports the development of an advanced assembly modelling environment for the purposes of manufacturing planning and analysis. computer-aided assembly process planning (CAAPP) is not a mature technology, despite the managerial and technical advantages offered by its implementation. This paper describes the limiting factors in industrial acceptance of CAAPP and discusses methodologies by which these factors can be eliminated. This is done primarily by the integration of CAAPP functionality with a product data management (PDM) tool, providing a data control framework and a high-level data structure to form the basis of planning. The paper also details a system based on the described methodologies. Data control methodologies are presented to aid retrieval, storage and creation. Methods for the definition of liaisons, mating features and fastener information are discussed. The methodologies used for constraint identification, process sequence generation and sequence representation within the system are described. Multiple sequences are represented by means of a tree structure, similar to the AND/OR graph representation. The sequence is navigable and can be used downstream to evaluate possible sequences of generate scheduling data. The underlying object-oriented model developed to facilitate automated assembly process planning is described in detail. more...

Background: Molecular characterization of metastatic tumors to investigate intra- and intertumor heterogeneity has proven more difficult than early stage disease as opportunities for surgical removal are limited. Rapid/warm autopsy programs that are conducted soon after death minimize tissue ischemia, thereby enabling procurement of high-quality viable tissue. To our knowledge, integrated proteo-genomics studies to characterize tumor heterogeneity of metastatic lung adenocarcinoma and thymic carcinoma are lacking. Methods: We sought to characterize and decipher mechanisms of intra- and intertumor heterogeneity of Stage IV lung adenocarcinoma and thymic carcinoma through whole exome sequencing, RNA sequencing, copy number estimation, and mass spectrometry-based proteomics of 38 tumors from five rapid/warm autopsy patients. The autopsy procedure was initiated between 2-4 hours of death. Results: One lung adenocarcinoma (RA003) and one thymic carcinoma (RA006) patient had high mutation burden and extreme mutational (SNV) heterogeneity. This was likely driven by APOBEC-mutagenesis. We constructed phylogenetic trees showing truncal, shared, and private SNVs and copy number alterations (CNAs). Interestingly, we discovered a pattern of recurrent, parallel but opposite arm level CNAs in different metastatic branches within a subset of patients (RA000, RA004, and RA006). In contrast, RA003 had only truncal CNAs and the least heterogeneity at the CNA level. Assessment of intra- and intertumor heterogeneity at the transcriptomic and proteomic levels revealed high concordance in gene expression and protein abundance within tumors from patient RA003 compared to patient RA004, potentially reflecting the downstream effect of CNA vs. APOBEC-induced mutations. Further analysis of cis vs. trans effects of CNA on gene expression and protein abundance in all the metastatic tumors revealed many trans-acting hot spots and limited cis effects, which is contrary to copy number effects on gene expression in primary lung adenocarcinoma tumors. Trans-acting hot spots differed between two major metastatic lineage of patient RA004, suggesting copy number changes may be responsible for high intermetastatic proteomic heterogeneity in this patient. Conclusions: Our results demonstrate ongoing mutational and chromosomal instability throughout the metastatic process of lung adenocarcinoma and thymic carcinoma. APOBEC mutagenesis was likely the primary driver of SNV heterogeneity. However, intertumor heterogeneity of metastatic disease at the level of the transcriptome and proteome occurred in association with CNA rather than mutational heterogeneity. APOBEC mutagenesis and CNA are complementary mechanisms of tumor evolution and heterogeneity affecting tumor metastasis. Citation Format: Nitin Roper, James Gao, Rouf Banday, Tapan Maity, Xu Zhang, Abhilash Venugopalan, Rajesh Patidar, Sivasish Sindiri, Constance Cultraro, Alexandr Goncearenco, Anna Panchenko, Romi Biswas, Jing Wang, Stephen Hewitt, David Kleiner, Bing Zhang, Javed Khan, Ludmila Prokunina-Olsson, Udayan Guha. Apobec-mutagenesis drives mutational heterogeneity while copy number alterations drive transcriptomic and proteogenomic heterogeneity in metastatic lung adenocarcinoma and thymic carcinoma [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A182. more...

The Ebola virus disease (EVD) epidemic killed almost 12,000 people across Sierra Leone, Liberia and Guinea, causing significant psychological distress and suffering. This paper describes International Medical Corps’ innovative and comprehensive model for integrating mental health and psychosocial support (MHPSS) considerations and activities into Ebola treatment units (ETUs) across Sierra Leone and Liberia. This includes staff capacity building as well as psychosocial considerations and activities to address needs and challenges at the ETUs. This model was aimed at reducing patient and family distress and promoting healthy behaviours and recovery. We also include data describing mental health-related symptoms reported by our ETU patients, as well as psychosocial support interventions utilised. We discuss recommendations and lessons learnt and conclude that in line with global guidelines, MHPSS considerations and activities should be integral to all aspects of EVD care. Key implications for practice Patients admitted to ETUs face several stressors and challenges related to the ETU environment and procedures, separation from families and effects of EVD Mental health and psychosocial support considerations should be an integral part of all aspects of care provided at the ETU Paraprofessional psychosocial support workers can play a key role in meeting patient needs at the ETU in line with global mental health and psychosocial support guidelines. more...

This paper reports part of the results of a 3 year project carried out at Cranfield University in collaboration with companies in the automotive and aerospace industry, aiming to develop new methodologies for computer aided assembly process planning (CAAPP). CAAPP is not a mature technology, despite the managerial and technical advantages offered by its implementation. This paper describes the limiting factors in industrial acceptance of CAAPP and discusses methodologies by which these factors can be eliminated. This is done primarily by the integration of CAAPP functionality with a product data management (PDM) tool, providing a data control framework and a high-level data structure to form the basis of planning. The paper also details a system based on the described approach. The underlying object-oriented model developed to facilitate automated assembly process planning is described in detail. Data control methodologies are presented to aid retrieval, storage and creation. Methods for the definition of liaisons, mating features, are discussed. The methodologies used for constraint identification, process sequence generation and sequence representation within the system are described. Multiple sequences are represented by means of a tree structure, similar to the AND/OR graph representation. The sequence is navigable and can be used for downstream sequence evaluation and simulation or to generate scheduling data. more...

Most of the important cost related design decisions are taken in the early design stages. More often than not, designers have little or no knowledge of the manufacturing difficulties. Therefore, a design engineer typically designs components without consideration for manufacturing difficulties. This paper describes a product data management (PDM) based system for manufacturing evaluation and analysis in the early design stages. The system is based on a process planning system and an embedded expert system to resolve the abstract data usually associated with the early design stages. The system will allow early measurement of design in terms of time, manufacturing cost and resources. Early measurement of design would be especially helpful in supporting new design techniques like simultaneous design and concurrent engineering. The system is being developed in industrial collaboration with LSC Group, UK, which is a pioneering company in the field of automated process planning using STEP (standard for exchange of product data) AP224 standard. more...

This paper describes the results of a project sponsored by the Engineering and Physics Science Research Council (EPSRC) in collaboration with leading engineering and consultant companies, which is aimed at developing new methodologies for Computer-Aided Assembly Process Planning (CAAPP). The aims of this project were to investigate contemporary industrial requirements for CAAPP, study the feasibility of integrating CAAPP with data management tools via a product model and review current state-of-the-art systems and methodologies. The research has been focused on finding solutions to some of the limiting factors that have kept CAAPP an immature technology for many years. The deliverable of the research project is a novel assembly planning system, which has been developed in a Product Data Management (PDM) environment. The system takes the product configuration model derived from the PDM system as the input. This input is analysed by the system using intensive built-in knowledge to yield detailed assembly pl... more...

Introduction: Intratumor heterogeneity has been characterized among multiple cancer types. However, in lung adenocarcinoma, recent work has been limited to early stage primary tumors and intertumor heterogeneity has not been well-studied. Most importantly, an integrated tumor heterogeneity analysis at the level of somatic variants, copy number, transcript and protein expression, and the phosphoproteome is outstanding. Methods: In order to characterize both intra-tumor and inter-tumor heterogeneity of metastatic lung adenocarcinoma, we applied whole exome sequencing, RNA-seq, CNV-seq and mass spectrometry-based proteomic analyses on 33 tumor regions from metastatic sites including lung, liver and kidney, obtained by rapid/warm autopsy from 4 patients with Stage IV lung adenocarcinoma. The autopsy procedure was initiated between 2-4 hours of death. Results: We found considerable intertumor heterogeneity with organ-specific, branched evolution that was consistent across DNA, RNA and protein analyses. Intratumor heterogeneity differed depending on oncogene-status: oncogene-negative tumors (without RTK/RAS/RAF mutations or known fusion gene) had significantly higher genomic intratumor heterogeneity than oncogene positive tumors. The degree of heterogeneity at the genomic and proteomic level was patient-specific. The proteomic analysis complemented genomic variants-based clonal evolution analysis. High-confidence driver mutations (KRAS, EGFR, TP53, CTNNB1) uniformly occurred early in the evolution of metastatic lung adenocarcinoma consistent with the concept of these mutations as likely ‘founders’. In contrast, other known driver mutations occurred more often in later stages among specific organ branches. Notably, oncogene-negative tumors carried significantly more driver mutations than oncogene-positive tumors suggesting that genomic alterations may have a larger role in the metastatic process versus the early evolution of lung adenocarcinoma in oncogene-negative vs. oncogene-positive tumors. Among all patients, lung cancer specific focal copy number alterations frequently occurred within metastatic branch points. Single metastatic site biopsies would therefore be unlikely to capture all significant driver mutations and copy number alterations, particularly among oncogene-negative tumors. Conclusion: Metastatic lung adenocarcinoma evolves through a branched, organ-specific, process with acquisition of significant driver mutations and copy number changes, particularly among oncogene-negative tumors. The branched evolution is ultimately influenced by proteomic and phosphoproteomic alterations affecting key signaling pathways that may not be always a result of genomic changes. Citation Format: Nitin Roper, Tapan K. Maity, James Gao, Abhilash Venugopalan, Xu Zhang, Romi Biswas, Constance Cultraro, David Kleiner, Stephen Hewitt, Javed Khan, Guha Udayan. Proteogenomic heterogeneity in metastatic lung adenocarcinoma revealed from rapid/warm autopsy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2927. doi:10.1158/1538-7445.AM2017-2927 more...

In the past the main processes in the introduction of a new vehicle into the market were developed by large manufacturers, or original equipment manufacturers (OEMs), and the vast majority of concurrent engineering (CE) research work was based on issues relevant to them. Today the situation has changed world-wide. Large companies outsource a great deal of high level engineering work to suppliers. This outsourcing is justified by lower costs and higher quality, and at the same time every company can use its resources in the areas it has technical expertise. However, most suppliers still follow the ‘build and break’ approach. The cost of introducing new approach such as CE, and adopting new technologies such as computer aided engineering (CAE) is substantial, as this cost adds to the operating costs and is only justifiable if it enables the development of higher quality products in less time with fewer people. The authors have examined a number of available CE frameworks and noted that these frameworks dealt with different aspects of CE in different degrees of detail. But they did not differentiate between the introduction of CE in large manufacturers on one hand and their suppliers on the other. This project is based on the recognition that a different approach to CE implementation is needed at the suppliers’ level. A three level framework has been proposed, i.e., (i) the environment in which the suppliers operate, (ii) a five stage implementation approach, and (iii) a CE tool portfolio. Implementation of the three level framework has started successfully at Tickford Engineering Ltd., which is a typical and fast growing supplier to the automotive industry. more...

Sheet metal is widely used for industrial and consumer products because of its malleability into complex shapes. However, in the aerospace industry manufacturing planning of sheet metal products is still mainly carried out manually. Most of the previous research in this field has been primarily devoted to computer aided process planning for rotational and prismatic parts. This paper describes the development of an advanced software toolset used for the automation of sheet metal fabrication planning for aircraft components. The system is specifically designed to be implemented and maintained by manufacturing engineers, rather than computer programmers. Therefore a systematic user requirement capture has been carried out, and the planning knowledge has been captured within a leading aerospace company, which was the main sponsor of the project. The prototype system was then developed in collaboration with a software consultant company and finally evaluated and benchmarked through industrial case studies which proved that the system provides an efficient and effective approach to sheet metal fabrication process planning, when compared with other commercially available systems. more...