Comparing lean and six sigma.
\r\n\tIn eukaryotic cells, the endoplasmic reticulum is an organelle adjacent to the nuclear membrane. This organelle is essential for calcium homeostasis and lipid biosynthesis and protein assembly, folding, and post-translational modification. The interplay between the endoplasmic reticulum membrane and the outer mitochondrial membrane, called mitochondria-associated endoplasmic reticulum membranes (MAMs), permits a wide range of cellular activity, including the division and fusion of mitochondria and the dynamic passage of lipids, glycogen, and calcium ions.
\r\n\tIt has been established that energy/nutrient depletion, calcium flux injury, or oxidative stress disrupt endoplasmic reticulum homeostasis and even induce accumulation of misfolded/unfolded proteins leading to endoplasmic reticulum stress. Under endoplasmic reticulum stress conditions, an adaptive mechanism of coordinated signaling pathways, defined unfolded protein response (UPR), is activated to return the endoplasmic reticulum to its healthy functioning state. The aging causes a decrease of the protective adaptive response of the UPR and an increase of the pro-apoptotic pathway together with endoplasmic reticulum ultrastructural injury. Controlling endoplasmic reticulum stress response, maintaining the appropriate endoplasmic reticulum ultrastructure and homeostasis, and retaining mitochondria interplay are crucial aspects for cellular health.
\r\n\tThis book presents a comprehensive overview of endoplasmic reticulum, including, but not limited to, endoplasmic reticulum ultrastructural anatomy, MAMs, endoplasmic reticulum stress, and their implication in health and diseases. Additionally, identifying perturbations in the endoplasmic reticulum stress response could lead to early detection of age-related disease and may help develop therapeutic approaches.
",isbn:"978-1-80356-228-5",printIsbn:"978-1-80356-227-8",pdfIsbn:"978-1-80356-229-2",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,hash:"5d7d49bd80f53dad3761f78de4a862c6",bookSignature:"Dr. Gaia Favero",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",keywords:"Metabolism, Aging, Neurodegenerative Diseases, Endoplasmic Reticulum, Microscopy, Metabolic Stress, Ultrastructural Anatomy, Cellular Stress, Contactology, Mitochondria, Cellular Stress, Endoplasmic Reticulum Response",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 9th 2022",dateEndSecondStepPublish:"May 6th 2022",dateEndThirdStepPublish:"July 5th 2022",dateEndFourthStepPublish:"September 23rd 2022",dateEndFifthStepPublish:"November 22nd 2022",remainingDaysToSecondStep:"14 days",secondStepPassed:!0,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Human anatomy researcher involved in crucial topics on morphology, anatomy, and molecular medicine - working on innovative approaches to aging-related pathopsychological processes at the University of Brescia.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"238047",title:"Dr.",name:"Gaia",middleName:null,surname:"Favero",slug:"gaia-favero",fullName:"Gaia Favero",profilePictureURL:"https://mts.intechopen.com/storage/users/238047/images/system/238047.jpg",biography:'Dr. Gaia Favero is a prominent scientist in the field of life sciences. 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Continuous improvement is the main aim for any organization in the world to help them to achieve quality and operational excellence and to enhance performance [2, 3].
It has changed manufacturing forever and from every aspect of the industry: from the people and the machinery to the logistics and administration. According to SAIL engineer Srivastva, “Machines mean nothing; if they are not efficient and calibrated—this is where the Six Sigma Methodology and the Machine Industry marry their goals for the betterment of the business industry”.
There is a misconception that Lean and Lean Six Sigma methodologies are only applicable to manufacturing or supply chain processes [4, 5]. However, these tools can be used within all aspects of a business [6]. The essential foundation needed for Lean and Lean Six Sigma methods succeed within all areas of a company is the capability to recognize waste, decrease the waste, and forcefully attempt to eliminate all activities that do not add value or increase customer satisfaction both within the company and outside.
These methods are not a new phenomenon. In fact, the Lean methodology has been an effective tool since the dawn of the industrial age [7, 8]. The idea of improving performance and meeting the expectations of customers while still improving the bottom line has always been the goal of businesses [9]. The evolution of Lean and Lean Six Sigma is based on understanding what methods or mixture of methods should be used to ensure the biggest impact to the business. The Six Sigma DMAIC (Define, Measure, Analyze, Improve, and Control) foundation is the base for our Lean training and service programs [10, 11].
Six Sigma basics are designed to improve manufacturing [12, 13]. This is a type of quality control that was originally developed for large scale manufacturers. It was intended to enhance processes and eliminate the amount of defects found within them. The Lean method is a philosophy centered around eliminating waste and providing the best customer experience [14]. According to the Lean manufacturing subject matter expert, there are eight kinds of waste: defects, overproduction, waiting, non-utilized talent, transportation, inventory, motion, and extra processing.
Researchers believe that it is very important to conduct a comprehensive review in manufacturing field to understand the each aspect of Lean Six Sigma. Research on “Lean Six Sigma in manufacturing” is limited and state that no standard work done for such a combination exists.
Hence, the aim of this chapter is to address such gaps within Lean Six Sigma (LSS) and manufacturing that allow them to achieve the most benefits from this strategy, as well as to identify the gaps and give recommendations for future research. To achieve the overall aims of this chapter, the author has comprehensively reviewed the literatures in second section.
The concept of lean thinking can be traced to the Toyota production system (TPS), a manufacturing philosophy pioneered by the Japanese engineers Taiichi Ohno and Shigeo Shingo [15, 16]. The development of this approach to manufacturing began shortly after the Second World War while employed by the Toyota motor company [17]. Lean manufacturing extends the scope of the Toyota production philosophy [18] by providing an enterprise-wide term that draws together the five elements of “the product development process, the supplier management process, the customer management process, and the policy focusing process for the whole enterprise” [17]. Lean Six Sigma has been defined as “a business improvement methodology that aims to maximize shareholders’ value by improving quality, speed, customer satisfaction, and costs: it achieves this by merging tools and principles from both Lean and Six Sigma” [19]. Gershon and Rajashekharaiah [20] point out that “leading texts fail to define Lean Six Sigma as a unique methodology”.
Laureani and Antony [21] stated that “Lean Six Sigma uses tools from both toolboxes in order to get the best from the two methodologies, increasing speed while also increasing accuracy”. Both Lean and Six Sigma require a company to focus on its products and customers [19]. According to Stoiljković et al. [22], the concepts of lean and six sigma are intertwined in that Lean speed enables Six Sigma quality and Six Sigma quality enables Lean speed. Pepper and Spedding [17] and Ferng and Price [23] similarly identify that Lean thinking may be used to identify areas of improvement and set standards, while the Six Sigma methodology may be used for targeting them and for investigating deviations from said standards. The foundation of the lean vision is still a focus on the individual product and its value stream (identifying value-added and non-value added activities), and the main target of lean thinking is to eliminate all waste, or muda, in all areas and functions within the system [16, 17].
Lean Six Sigma is a combination of two powerful process improvement methods: Lean and Six Sigma [24, 25, 26]. It decreases organization’s costs by:
Removing “Waste” from a process: Waste is any activity within a process that is not required to manufacture a product or provide a service that is up to specification [36, 37].
Solving problems caused by a process: Problems are defects in a product or service that cost your organization money [36, 37] (Figure 1).
Lean, six sigma and lean six sigma. Source: [
Lean and Six Sigma are the two most important continuous improvement (CI) methodologies for achieving operational and service excellence in any organization [29, 30, 31, 32, 33]. LSS is the fusion of two most powerful process excellence methodologies, namely, Lean and Six Sigma [24].
According to Sokovic and Pavletic [34]
Six Sigma is a well-established approach that seeks to identify and eliminate defects, mistakes or failures in business processes or systems by focusing on those process performance characteristics that are of critical importance to customers’ [35]. It is a statistical methodology that aims to reduce variation in any process, reduce costs in manufacturing and services, make savings to the bottom line, increase customer satisfaction, measure defects, improve product quality, and reduce defects to 3.4 parts per million opportunities in an organization [35, 36].
The high cost of Six Sigma training is a barrier for many organizations to deploy this methodology [37, 38]. In fact, deploying Six Sigma in isolation cannot remove all types of waste from the process, and deploying Lean management in isolation cannot control the process statistically and remove variation from the process [35]. Therefore, some companies have decided to merge both methodologies to overcome the weaknesses of these two methodologies when they have been implemented in isolation and to come up with more powerful strategy for continuous improvement and optimizing processes [35, 39, 40]. In fact, LSS are completing each other and there is an obvious relation between both methodologies, which makes it possible for the synergy of the two methodologies (see Figures 2 and 3). Therefore, the integration of these two approaches gives the organization more efficiency and affectivity and helps to achieve superior performance faster than the implementation of each approach in isolation [30, 35, 41].
Concept of lean six sigma. Source: [
Lean and six sigma popularity and integration. Source: [
Salah et al. [30] has indicated that the integration of lean and Six Sigma is the solution to overcome the shortcomings of both, as they complete each other. This integration helps companies to achieve zero defects and fast delivery at low cost. According to Bhuiyan and Baghel [42] the combination of this two is the way for organizations to increase their potential improvement.
The integrated approach to process improvement (using Lean and Six Sigma) will include:
Using value stream mapping to develop a pipeline of projects that lend themselves either to applying Six Sigma or Lean tools [34, 43].
Teaching Lean principles first to increase momentum, introducing the Six Sigma process later on to tackle the more advanced problems [34, 43].
Adjusting the content of the training to the needs of the specific organization—while some manufacturing locations could benefit from implementing the Lean principles with respect to housekeeping, others will have these basics already in place and will be ready for advanced tools [34, 43].
The following roadmap provides an example for how one could approach the integration of Lean and Six Sigma into a comprehensive roadmap (Figure 4).
Integrating lean and six sigma roadmap. Source: [
Therefore, many manufacturing firms are looking for an approach that allows to combines both methodologies into an integrated system or improvement roadmap [44, 45]. However, the differences between the Six Sigma and Lean are profound (Table 1).
Lean | Six sigma | |
---|---|---|
Goal | Create flow and eliminate waste | Improve process capability and eliminate variation |
Application | Primarily manufacturing processes | All business processes |
Approach | Teaching principles and “cookbook style” implementation based on best practice | Teaching a generic problem-solving approach relying on statistics |
Project selection | Driven by value stream map | Various approaches |
Length of projects | 1 week to 3 months | 2–6 months |
Infrastructure | Mostly ad-hoc, no or little formal training | Dedicated resources, broad-based training |
Training | Learning by doing | Learning by doing |
Comparing lean and six sigma.
Source: Prepared by the author.
Duarte [46] identify that Lean Six Sigma has become a widely recognized process improvement methodology and has been adopted by many companies like Ford, DuPont, 3 M, Dow Chemicals, and Honeywell etc. At present, the methodology of Lean Six Sigma has been carried out in 35% of companies listed in the Forbes top 500 [46]. He illustrates how Lean tools can be incorporated into the Six Sigma DMAIC (Define, Measure, Analyze, Improve, and Control) cycle (Figure 5).
Integrating lean tools and six sigma DMAIC cycle. Source: [
In the efforts to draw nearer to customers, several manufacturers have lost focus on what ought to be a company’s primary success factor—profitable growth. In today’s competitive manufacturing environment, it takes more than quick fixes, outsourcing and downsizing for firms to systematically achieve their growth and profit objectives [47]. Whereas these choices could yield temporary financial relief, they will not lead the way to long-term growth and profitability. Therefore, they have to bring lean to grow and continually exceed bottom line expectations; and to bring lean they must master eight basics of Lean Six Sigma for manufacturing.
In digital and cloud based environment, the physical database is replaced by a virtual database. Data are transferred throughout the cloud computing [48]. Organizations were led to believe that computerized systems would provide the solution to all growth and profit challenges. Material requirements planning (MRP) and enterprise resource planning (ERP) system gurus assured companies that if they implement their software programs at bottom line, would take care of itself. In a typical company, converting the quarterly financial forecast into reality still requires overtime, internal/external expediting, last minute “on-the-run” product changes and even some “smoke and mirrors” from time to time [49]. Results are scrap, rework and warranty costs that negatively impact profitability and quality, and shipment problems that deliver less than acceptable customer satisfaction [47]. Companies have spent thousands of dollars in pursuing MRP and ERP only to see growth and profits decline due to uncontrolled operating costs that produced non-competitive pricing [39, 40]. Thus, softwares can be a solution for these problems, and eliminate the root causes of ineffective systems and processes.
Manufacturers can get the root causes by in-depth understanding of the fundamentals of Six Sigma and then a total reliable commitment and determined execution of eight basics of Lean Six Sigma. Like renowned football coach Vince Lombardi, who achieved success by having his team focus on the mastery of football basics, manufacturing teams need to focus on the mastery of the Lean manufacturing basics. These basics require proactive planning and inflexible implementation that demands leadership above and beyond just satisfying day-to-day accountabilities. Some managers cannot imagine the benefits of mastering manufacturing basics. Others simply cannot find the time. Like practicing blocking and tackling in football, it is not exciting. And like most football heroes, managers prefer to run with the ball. But without the solid execution of Lean Six Sigma basics, companies will seldom achieve their full growth and profit potentials [44, 47]. Here are the eight basics of Lean Six Sigma which every manager should know and implement:
Lean six sigma principles mainly refer to process improvements, although their practical implementation has different impacts according to different organizational models [56]. Leaders at all levels are working to integrate lean and Six Sigma principles into all business processes, including product design and development, integrated supply chain, marketing and sales, customer service, infrastructure, governance and strategy deployment [57].
According to Lucid chart Content Team, for a process stream that produces the best results; consider the following Lean Six Sigma principles for your organization.
Womack and Jones [59] has summarized five Lean Six Sigma Principles in “Lean thinking—banish waste and create wealth in your corporation” as follows:
Womack et al. [60] defined the five principles of Lean manufacturing in their book “The Machine That Changed the World”. The five principles are considered a recipe for improving workplace efficiency and include: (1) defining value, (2) mapping the value stream, (3) creating flow, (4) using a pull system, and (5) pursuing perfection. The principles encourage creating better flow in work processes and developing a continuous improvement culture. By practicing all these five principles, an organization can remain competitive, increase the value delivered to the customers, decrease the cost of doing business, and increase their profitability. These Lean principles can be applied to any process to reduce the wastes (Figure 6).
The five lean principles [
Lean six sigma is a systematic data driven methodological philosophy centered around eliminating waste, reducing process variation [61] and providing the best customer experience [45]. According to the Lean method, there are eight kinds of waste: defects, overproduction, waiting, non-utilized talent, transportation, inventory, motion, and extra processing [62]. Lean six sigma is a structured problem solving methodology [63]. The lean six sigma framework aim at providing an effective approach to integrating lean and six sigma [65]. It uses the DMAIC phases similar to that of Six Sigma [32]. Problem solving in lean Six Sigma is done using the DMAIC framework. It has been implemented and verified at one engineering company in UAE [32]. The results show that the process “Make-to-Order (MTO) projects” has a long lead-time [32]. The main causes of the long lead-time are the subcontractors, the customers, and the company-implemented procedures [32]. Using the framework, it was possible to identify the most significant reason for the long lead-time, analyze the root-cause(s), suggest three relevant solutions and select the most preferred one [32]. In this methodology framework application, lean-production, six-sigma, balanced scorecard, simulation and cost benefit analysis tools were used.
A study was conducted in India by Ben Ruben et al. [61] using DMAIC framework methodology and validated practically to provide both operational and environmental benefits. The framework is validated with an industrial case study conducted in an Indian automotive component manufacturing firm/organization located at Tamilnadu. The firm manufactures high precision transmission. On the successful deployment of the framework, the internal defects was brought down to 6000 ppm from 16,000 ppm and environmental impacts was reduced to 33 Pt from 42 Pt. Deployment of the developed framework helped in improving the firm’s sigma level and also reduced the overall environmental impacts. In this research different lean six sigma tools were used at different level/phase like-Value Stream Mapping (VSM), 5S, Kaizen, Cause and effect diagram, Quality Function Deployment (QFD), High level SIPOC, Eco-QFD, Pareto chart, Environmental VSM (current level), life Cycle Impact Assessment, Brainstorming, Design of Experiments, Cost benefit analysis, Design for Environment, Life Cycle Interpretation, Environmental VSM (Future level), 7s practices, Standard operating Procedure (with environmental metrics) and Performance evaluation tools.
Thus, using the framework methodology the user will have a systematic approach for continues improvement. Because, this framework also allows the user identify the process problem(s) and solve them effectively [32]. There are five stages in this framework. They are Define, Measure, Analyze, Improve, and Control [66] (Figure 7).
Lean six sigma framework and methodology. Source: [
Hill et al. [45] has developed an initial conceptual Lean Six Sigma Framework (LSSF) and undertook a series of iterative developments in an attempt to improve its effectiveness and suitability to Maintenance Repair and Overhaul (MRO) implementation. Hill et al. [45] describes the novel implementation of an integrated LSS framework and outlines how it was used to identify the factors that affect supply chain performance in an aerospace Maintenance Repair and Overhaul (MRO) facility. It shows how each of the Six Sigma DMAIC phases are applied systematically to each of the Lean stages. Stage (0) of the LSSF was the starting point of the implementation stage.
Integrated generic lean six sigma framework (LSSF). Source: [
Hill et al. [45] outlined the application and measures the effectiveness of the integrated LSS framework through its ability to achieve new and enhanced performance through simultaneously reducing late material calls and reducing and stabilizing Order To Receipt (OTR) times.
Lean and Six Sigma both have their own set of tools and techniques that can enhance a company’s objectives for value and profit enhancement [24]. Lean six sigma consists of many tools and techniques for continuous improvement such as the Kanban system, 5S, Cause and Effect analysis (C&E), Value Stream Mapping (VSM) and many others [35, 36]. According to Brazilian publications, there are six most frequently tools used in LSS applications: “Control Charts”, followed by “Value Stream Mapping”, “DMAIC,” “Kaizen,” “Ishikawa Diagram,” and “Histogram;” and Control chart is the top ranking tool [33]. DMAIC is a five step method for improving existing process problems with unknown causes. DMAIC define and quantify the problems; identify cause of the problems; implement, verify and maintain the solutions. The DMAIC or DMADV toolkit comprises all the Six Sigma and Lean tools [10], and the success factors of lean six sigma is their ability to use the toolbox in a systematic and disciplined manner [10]. Quality Function Deployment (QFD), Failure Mode and Effect Analysis (FMEA), Statistical Process Control (SPC), Design of Experiments (DOE), Analysis of Variance (ANOVA), Kano Model, etc. statistical tools and techniques reduce variation in any process, reduce costs in manufacturing and services, make savings to the bottom line, increase customer satisfaction, measure defects, improve product quality, and reduce defects to 3.4 parts per million opportunities in an organization [35, 39]. Some of these tools have adopted from TQM as Six Sigma in itself has derived from the TQM movement. All the tools and techniques are shown in Table 2.
Lean Six Sigma (LSS) tools | Author(s) |
---|---|
Control Charts | [10, 24, 33, 67] |
Value Stream Mapping (VSM), Box plot, Process mapping, Standardized work, Scatter diagram, Cause and effect matrix (C&E analysis), Kanban system, Hypothesis Testing, Process Flow Diagram, Quick, 7 waste analysis, Heijunka | [10, 24, 31, 35, 67] |
DMAIC or DMADV | [10, 24, 67, 68] |
Kaizen, Single Minute Exchange of Die (SMED) | [24, 67, 68] |
Ishikawa Diagram, Histogram, Stratification | [10, 24] |
Pareto Chart, E-Kanban system, SOP, Check sheet, VOC translation matrix, Three diagrams, Brainstorming, SIPOC Diagram | [10, 24, 31] |
Current state map, Spaghetti diagram, Poka-yoke | [24, 67] |
5S, 5 Whys, XY matrix, FMEA, ANOVA, Design of Experiments (DOE), Rootcause Analysis, Mistake proofing, VSM, Pareto chart, CTQ analysis, Root-cause analysis, Jidoka | [10, 24, 31, 35, 67] |
Process Capacity Analysis, Cause and effect diagram | [10, 24, 31] |
Changeover, Total Productive Maintenance (TPM), Line balancing; Cellular manufacturing, | [24, 67] |
Critical to Customer Tree—VOC/VOB | [24] |
OEE, DMADV, Autonomation (Jidoka), Visual management | [24] |
5W1H, JIT, Regression analysis, QFD, Statistical Process Control (SPC), Kano Model, Gemba (Go & See) | [24, 31, 35, 39, 67, 68] |
Confidence Interval, Continuous Flow, Benchmarking | [24] |
Impact Effort Matrix, PDCA, DFSS, Production Leveling, Lean Office, Solution Prioritization Matrix, Matrix Diagram, | [24] |
QCC (Quality Control Circle), Cellular Layout, Milkrun, Mizusumashi | [24] |
Andon, QC Story, Routine Management, R&R, Gantt Chart | [67] |
Relationship Diagram, Stratification, Cross-functional Team, Theory of Constraints (TOC) Principles, A3 Form, Affinity Diagram | [67, 69] |
Identified lean six sigma tools and techniques.
Source: Prepared by the author.
There are many studies have been conducted on critical success factors of LSS. Author has shown critical success factors that were identified by previous researchers. Some of the predominant CSFs are discussed in this section.
Most studies on critical success factors (CSFs) have found senior management involvement and commitment as a CSF in the implementation of lean six sigma projects [10]. Carleysmith et al. [70] and Mustapha et al. [10] noted that senior support as a critical factor that enables the process of LSS implementation. Mustapha et al. [10] also identified senior management supports as the most vital institutional factors which enable implementation of the LSS framework. Delgado et al. [71] says that the role of management is influencing the practice and guiding organizational culture to help the organization in closing the gap and proposing ideas for improvement.
According to Mustapha et al. [10] and Sharma [72] senior management involvement ensures the benefit of the program to the company by facilitating trust and communication. Senior management motivates to the team members, enables them to use procedures and methods for better quality. They also ensure recognition, which leads to effective and quicker change toward greater innovation [10]. Mustapha et al. [10] and Zu et al. [73] have also considered Management decisions and Organizational infrastructure in the lean critical success factors.
Näslund [68] frequently mentioned CSFs include the importance of a vision and strategy, top management support and commitment, importance of communication and information, and so forth. According to Mustapha et al. [10] linking business strategy with continuous improvement strategy is important. A clear and solid combination of LSS with the company’s corporate strategy is the most critical factor for successful implementation.
Kumar et al. [74] and Mustapha et al. [10] note that stress on overall program success and short-term successes are important in the initial stages of LSS to ensure members’ interest in the lean project. Apart from these LSS projects also need champion or sponsors who provide direction to the implementation team, find resources and plan for the project [10]. The readiness of the company is also a critical in lean implementation [10, 68, 75].
For the successful implementation of change effort, different education and training are also most required factors [68, 72, 74]. Education in a systems and process view of organizations answers the questions why the change of the system is needed, how it is supposed to change, and what the benefits will be to the system [68]. This education can also prepare the organization for change and create the readiness for change [68].
Customer satisfaction as the central goal of LSS, Cultural change and a transformation of attitudes of the employees [10, 74], productive teamwork [76], LSS working groups [74], duties and responsibilities of team players [74], Integration of LSS with the performance management process [10] and integration of human and process elements of improvement [10, 77] are the key element for the effective implementation of LSS programs. Because when these elements are combined with other aspects of LSS, it would produce its successful implementation in an organization.
Lean Six Sigma combines the strategies of Lean and Six Sigma [30]. It has rapidly established itself as the key business process improvement strategy of choice for many companies [45]. In general, the approach has been to align Lean Six Sigma deployments with the strategy of the organization [46]. The strategy usually includes a plan that addresses the high level goals of the organization [46]. Strategic objectives are then broken down into routine metrics at the operational level. In classic Six Sigma terminology the “Big Y” is broken into “smaller y’s” and plans are put in place to address each “small y” at the operational level. The majority of the companies use this approach in creating a Six Sigma portfolio that helps meet the strategic goals of the organization [46]. Both Lean and Six Sigma are key business process strategies which are employed by companies to enhance their manufacturing performance [78]. Table 3 illustrates different deployment approaches that are used along with some of the pros and cons of using the approach [46].
Lean six sigma deployment strategies. Source: [46].
Some companies use a top-down LSS deployment approach which is driven by strong governance [46]. For example: General Electric. This approach requires strong executive commitment and company wide acceptance to change [46].
The reasons for deploying LSS often include poor financial performance, retreating customer satisfaction, increased rivalry or the existence of a burning problem area [46]. There is not a single method that fits all Lean Six Sigma deployments. There are various deployment models that are broadly used in the industry today. Figure 9 illustrates a deployment strategy that includes a few concepts presented above.
Strategic goals and objectives in deployment wave. Source: [
The strategy includes a pilot or proof of concept phase and ends with a companywide LSS deployment. In the pilot phase, specific problems are addressed to reveal the usefulness of the methodology and to gain buy-in. larger investments are made in infrastructure, education and training of yellow belts, green belts, black belts and master black belts [46]. Organizations must be aware of their toolset and enhancements needed to move forward. Many organizations train their Black belts on the theory of constraints and agile techniques to keep their toolset sharpened with a goal of including various manufacturing engineering methodologies. For truly successful LSS, the deployment must be tied into the strategy and be focused on the right parts of the business [46].
Implementation of LSS is not a game of self interest. Thus, lean six sigma readiness must be assessed before its implementation in manufacturing organizations. Sreedharan et al. [79] recently designed an evaluation model in their quality paper “Assessment of Lean Six Sigma Readiness (LESIRE) for manufacturing industries using fuzzy logic”. According to this evaluation model, the following criteria must be for readiness of LSS in manufacturing:
Employee engagement
Developing organizational readiness
Establishing Lean Six Sigma dashboard
Roadmap for project execution
Infrastructure
Top management commitment and Involvement
Knowledge about Lean Six Sigma benefits
Good leadership
Clear vision and future plans
Proper communication about future benefits expected from project by top management
Experience in Lean Six Sigma deployment and implementation
Lean Six Sigma facilitator Structure
Alignment between the objective of the project and strategic objective of the company
Customer focus
Selection of candidate for Belt training
Project prioritization
Every organization is unique, without a common blueprint that universally applies. Lean Six Sigma implementation refers to a company’s management philosophy and a long-term strategy [80]. It can be implemented in any SMEs in phases. The aim of implementation of LSS is finding wider application in many different environments. A successful implementation has several factors associated with it. Alkhoraif [80] has noted that Japanese automobile companies Toyota have a high implementation success rate due to their inflexibility in systematic planned management of employees, resources and equipment.
In a Lean Six Sigma SMEs, people deal with process improvement by conducting improvement projects as well as continuously improving daily routine. This requires an organization which understands the methodology.
According to Lokesh R, There are eight steps to a successful lean six sigma implementation in SMEs. Lokesh R is a certified Black Belt and general manager of process excellence at Firstsource Solutions Ltd. The first step in a Lean Six Sigma implementation is deciding to use the methodology. Once the leadership of a SMEs believes they can benefit from using Lean Six Sigma, they can follow eight steps—Step 1: Create a Burning Platform; Step 2: Put Resources in Place; Step 3: Teach the Methodology; Step 4: Prioritize Activities; Step 5: Establish Ownership; Step 6: Take the Right Measurements; Step 7: Govern the Program; and Step 8: Recognize Contributions (Figure 10).
Successful lean six sigma implementation steps source: Prepared by the author.
Lean principles, tools and techniques have become a benchmark for manufacturing companies that have founded on the success of the Toyota Production System (TPS). Despite its popularity, companies are still struggling to achieve a successful lean implementation [81]. Many studies claim regarding the effectiveness of LSS in manufacturing and found that LSS practices is difficult and organizations encounter several roadblocks in this long continuous improvement journey. Some studies identified determining factors which make LSS journey either a success or a failure [82]. Existing research indicates some important organizational and technical barriers such as lack of management support and commitment, poor involvement of employees, and excessive confidence in lean tools and practices [81]. According to Navarro (a certified LSS Black Belt), there are five major barriers/obstacles/challenges to implement LSS in manufacturing:
Insufficient management time to support lean
Not understanding the potential benefits of applying lean
Underestimating employee attitudes/resistance to change
Insufficient workforce skills to implement lean
Backsliding to the old inefficient ways of working
Many organizations have reported significant benefits after the implementation of LSS in manufacturing [79]. Lean and LSS is not just for manufacturing. It can benefit organizations of any size, in any industry. Because all organizations have problems to solve, all organizations have waste, and all organizations want to increase profits and reduce costs. It benefit to Healthcare, Financial services, Retail and hospitality, Education and Office-based businesses. LSS can also benefit organizations in Agriculture, Energy, Mining, Construction, Consulting, Design, Hotels, Travel and transportation, Law firms, Logistics, Government and Public services.
Albliwi et al. [35] has conducted a review research on LSS. They reviewed 37 LSS original research papers including 19 case studies had been published in the manufacturing sector in 11 different countries, which are: USA, UK, India, The Netherlands, China, Malaysia, Australia, Iran, Taiwan, Sweden and New Zealand. Albliwi et al. [35] identified more than 50 benefits (in 19 case studies). The top 10 benefits are:
Increased profits and financial savings;
Increased customer satisfaction;
Reduced cost;
Reduced cycle time;
Improved key performance metrics;
Reduced defects;
Reduction in machine breakdown time;
Reduced inventory;
Improved quality; and
Increased production capacity.
Other identified benefits are identifying different types of waste, development in employee morale toward creative thinking and reduction in workplace accidents as a result of housekeeping procedures.
Many other LSS practitioners, manufacturers, academic researchers have realized common benefits in manufacturing by applying a successful lean methodology are—Greater productivity, Smoother operations, Greater flexibility and responsiveness, Eliminates defects, Improved product quality, Reduced lead time, Increased customer satisfaction, Improved staff morale, Safer working environment and Boosts bottom line.
Ben Ruben et al. [61] identified that on successful deployment of the LSS framework in an Indian automotive component manufacturing organization, the internal defects was brought down to 6000 ppm from 16,000 ppm and environmental impacts was reduced to 33 Pt from 42 Pt.
Lean and Six Sigma offers a number of substantial benefits to organizations. Most importantly, Lean and Six Sigma Creates efficient processes so you can deliver more products to customers; Increases revenue by streamlining processes; Reduces costs by eliminating waste activities; Develops effective teams by empowering employees, staff morale and job satisfaction.
Singh and Rathi [28] have recently conducted a review research on LSS and covered papers from 2000 to 2018. They have selected a total of 216 research papers published in different countries on LSS implementation in various manufacturing sector such as automotive, micro small medium enterprises, health care, education, financial sectors etc. and observed major LSS benefits are: reduction in inventory; reduced costs of poor quality; improve customer highest satisfaction; reduced cycle time and lead time; defect free processes; and improvement in productivity.
Many authors have argued that there are a significant number of limitations in LSS methodology. They have addressed many fundamental limitations [35]. These limitations can be a rich area for future research. The identified top seven limitations of LSS in the manufacturing sector are:
The absence of clear guidelines for LSS in early stages of implementation.
Lack of LSS curricula.
Lack of understanding of the usage of LSS tools and techniques.
Lack of a roadmap to be followed—which strategy first?
The limited number of practical applications of LSS integrated framework.
No globally accepted standards for certification.
Lack of expertise.
Thus, LSS practitioners need a clear guide for the direction of the early stages: which strategy should come first, Lean, Six Sigma or LSS, and what tools in the toolbox should be used first.
A Lean and Six Sigma practitioner’s “belt” refers to their level of experience. They may be a white, yellow, green, black, or master black belt. These roughly correspond to their hierarchy in martial arts.
This study is the first comprehensive review of existing reliable literatures on different aspects of lean six sigma and the issues emerging in this field published during the period 1990 to 2019 and extract theoretical elements to develop the concept of LSS. The future of lean six sigma depends on the development needs of organization involved. These needs and opportunities are creating emerging trends in LSS which includes:
The Big Data trend in lean six sigma
Green lean six sigma
Global Warming, Pollution and Lean’s impact
Lean and Six Sigma with environmental sustainability
Lean’s Impact on Resources
Energy Conservation and management by LSS
Factors affecting green lean six sigma
Integration of LSS into educational systems.
Assessment of LSS Readiness using fuzzy logic
Green supply chain management
To encourage research in the field of lean six sigma and manufacturing, here we are highlighting gaps in the existing literature as a basis for developing a research agenda.
Research gap 1 (performance measurement system for a particular organizations and processes);
Research gap 2 (application of LSS in developing SMEs);
Research gap 3 (integrated universal methods of manufacturing, frameworks, and models)
As LSS was implemented world over for improving performances of various processes, developing countries have also started implementing LSS and got significant results in various sectors [83]. Lean Six Sigma (LSS) methodology was recently applied to an Auto ancillary conglomerate in India for achieving operational excellence. The root causes for the problem were identified and validated through data based analysis from LSS tool box. The application of LSS methodology resulted in reduction of drilling defects while machining injector bodies and reduced the Defects Per Million Opportunities from 38,000 to 5600. The application of this methodology had a significant financial impact (saving of about INR 1.4 million per annum) on the bottom-line of the company [83].
All type of manufacturing industry can increase profits, reduce costs and improve collaboration using LSS. For reference, below is Lean Six Sigma success examples in the Manufacturing industry organized systematically (Table 4).
General Electric | Dell India Pvt. Ltd. | NALCO |
---|---|---|
Xerox | Colgate Palmolive | Steel Authority of India |
Ford | Al fanar | HP |
Toyota | Alessa | Seimens |
Durgapur Steel | Zuari Agrochemicals | 3 M (American MNC) |
BEML (Bharat Earth Movers) | Brother Gas | Acme Industries |
ADCO (Abu Dhabi oil Company) | Gulf Gas | AEDC |
AMRDEC | Wabash National Corp. | Gooch & Housego |
Axalta Coating Systems | Fortress Paper | Ingersoll Rand |
Barcoding Inc. | General Cable | Jabil Shanghai |
Beverage Producers | GKN Sinter Metals | John Sisk & Son |
Bosch | Milling Products | KushCo Holdings, Inc. |
Celestica | Molded Devices, Inc. | Foster Threaded Products |
Cummins | Real Alloy | Seegrid |
Luvata | Reliable Plant | Spanbild |
MC Assembly | Santana Textiles | The Jubach Company |
Magline | Think Lightweight | The National Productivity Centre of Nigeria |
Masonite | Topper Industrial | UTC Aerostructures |
Metform Engineers | Universal Machining Industries Inc. | Vermeer Corp. |
Lean six sigma success examples in the manufacturing industry.
Source: Prepared by author (adopted from [84]).
Lean Six Sigma is a combination of two powerful process improvement methods: Lean and Six Sigma. It decreases organization’s costs by removing “Waste” from a process and solving the problems caused by a process. Lean Six Sigma (LSS) is an emerging extremely powerful technology which is used to identifying and eliminating waste, improving the performance, efficiency and customer satisfaction to sustain in competitive manufacturing and nonmanufacturing environment. The focus of this chapter was to explore the each aspect of LSS in manufacturing. This systematic comprehensive review aims to synthesize, organize and structure the stock of knowledge relating to Lean Six Sigma and manufacturing. The identified lean six sigma tools and techniques, methodologies, frameworks, success and failure factors and strategies can be effectively used as a roadmap in manufacturing sector. This is also identified that the LSS has been implemented worldwide and in all type of manufacturing organizations for achieving the excellence. They have been successfully achieved their LSS objectives. But there are various challenges and barriers have been identified in the deployment of LSS. Assessments of lean six sigma readiness and implementation steps are most important that every practitioner must be aware. Basics of lean six sigma are discussed to get the root causes by in-depth understanding of the fundamentals of Six Sigma.
To bring lean in the organizations, every manager must be master and implement the eight basics of Lean Six Sigma for manufacturing. They should achieve their goal of satisfying/delighting customers by delivering higher quality service in less time by improving related business processes, eliminating defects and focusing on how the work flowed through the process.
This can be achieved only if the creativity of the people is used in team work on the processes with data and with an understanding of customers and processes. Therefore, the team members should work together to create real solutions for the organization. They should be from the different process areas, and their decisions should be based on data and facts.
Furthermore, for future direction, research and practitioners can be more focused on prioritization of significant barriers as identified in chapter and to tackle them during LSS implementation in manufacturing so that continuous improvement can be easily achieved [1].
Alveolar soft part sarcoma (ASPS) is a rare orphan malignant soft tissue tumor of uncertain cellular lineage representing 0.5–1% among soft tissue sarcomas and with a somewhat indolent yet lethal clinical course. It was first described in 1952 by Christopherson, a fellow in surgical pathology at Memorial Sloan Kettering Cancer Center, who reported 12 cases with similar clinical and pathology features [1]. It occurs mainly in adolescents and young adults between 15 and 40 years of age. For localized disease, the survival rate is 71% at 5 years and falls at 20% at 5 years for metastatic disease [2].
At diagnosis, a patient with ASPS describes a slow-growing mass in the extremities. Tumors in adults are most frequently involved located in the deep soft tissue of the lower extremities, especially the thigh and buttock [2]. This stands in contrast to the pediatric population where the tumor clearly has a predilection for the head and neck, and in particular the tongue and orbit [3]. ASPS has also been described as a rare primary lesion of the calvarium [4] and the pleura [5]. In the viscera, occurrences have been reported in such diverse anatomic sites as liver [6], lung [7], gastrointestinal tract [8], breast [9], uterine corpus [10], cervix [11], and the bladder [12]. Some deeply seated tumors may be quite large whereas those located in the head and neck area and viscera usually measure much less.
Preferential sites of metastatic sites are lung, bone, and frequently the brain. Metastases have been reported even 15 years after primary tumor diagnosis [2].
ASPS consists of nests of large rounded cells sometimes associated with characteristic crystalloids and embedded in a finely capillarized stromal background. The molecular genetics aspect involves the recurrent unbalanced translocation der(17)t(X;17)(p11;q25) [13]. The female predominance could theoretically be based on the statistical observation that the risk of a translocation involving the X chromosome present in two copies is greater in women [14]. No differentiation lineage is established according to the WHO classification of soft tissue tumors [15] although as is well-known differentiation patterns are the basis of most of the histopathological classifications of sarcomas.
After the original description of the lesion, one of the prevailing hypotheses, now totally abandoned, concerned its alleged myogenic phenotype which had fueled the unresolved question of its histogenesis. Masson had first numbered this tumor among muscle lesions [16]. Much data then seemed to uphold striated muscle differentiation based on different observations. Immunohistochemistry and immunofluorescent techniques showed cytoplasmic expression of muscle-associated proteins, such as desmin, muscle-specific actin, MM isozyme of creatine kinase [17, 18, 19, 20, 21, 22, 23, 24, 25], and nuclear expression of the skeletal muscle-specific regulatory protein MyoD1 [23]. The myogenic hypothesis was ultimately set aside for the following reasons. Desmin is not considered a reliable marker of skeletal muscle tissue differentiation and can be found expressed as well in smooth muscle proliferation, rhabdoid tumors, Ewing sarcoma, or neuroblastoma [26]. As for the nucleophosphoproteins MyoD1 and myogenin, no subsequent studies confirmed positivity. In the 12 cases reported by Wang et al. [27] and the 19 cases reported by Gomez [28] et al. immunohistochemical nuclear expression was completely absent. These authors observed nonspecific granular cytoplasmic staining linked to aberrant cross-reactions with unrelated antigens. In their studies, western blotting failed to highlight the 45-kd band of MyoD1, and MyoD1 transcript has not been detected by northern blot analysis [20]. Neither had ultrastructural myofilaments been observed in alveolar soft part sarcoma [27, 29]. The ultrastructure of the crystalloids supposedly composed of Z-band tropomyosin B, similar to rod structures seen in rhabdomyoma [30] seemed to favor muscle differentiation but new data demonstrated the absence of tropomyosin [31]. Some subsequent gene expression profiling studies momentarily revived the concept of muscle cell differentiation with the identification of differentially expressed genes [32, 33]. But later studies failed to validate these findings [34].
One report of expression profiling analysis suggested a neural differentiation because of marked expression of the transcription factor PAX6, an activator of neural genes [35, 36]. Curiously a neural crest origin had already been speculated [37].
DeSchryver-Kecskemeti et al. described ASPS as “malignant angioreninoma.” Indeed fluorescein-tagged antirenin antibodies in tumor cell were detected [38]. However, patient arterial hypertension was missing, and no tumor renin secretion (whether active or inactive) was biochemically revealed [31]. ASPS had also been labeled, albeit incorrectly as “malignant myoblastoma,” “granular cell myoblastoma,” “malignant granular cell myoblastoma” [39, 40, 41], or as “malignant tumor of the non-chromaffin paraganglia” [42].
When excised, ASPS has a soft consistency with encapsulated borders. The cut surface has a white to yellow–brownish color tinged with hemorrhagic spilling or central necrosis in large tumors (Figure 1a).
ASPS : gross pathology (cut surface) (a), typical cytoarchitectural features (b-j) and TFE3 immunohistochemical nuclear staining (k).
ASPS shows a distinctive recognizable morphology in most cases with nests or trabeculae (Figure 1b,c, and e) of large epithelioid round cells displaying an alveolar (Figure 1d) and sometimes dyscohesive appearance (Figure 1d and h). The stroma has a delicate vasculature with frequent lymphovascular invasions (Figure 1j). Typical cytoarchitectural aspects include individual monomorphic tumor cells with an abundant granular eosinophilic or clear glycogen-rich cytoplasm, sharp cytoplasmic borders, no striations, and an eccentric vesicular nucleus containing a prominent central nucleolus. In some cases, sheets of contiguous tumor cells may appear solid (Figure 1f and g), a finding more conspicuous in children. Cells can be multinucleated (Figure 1h). Mitoses are few and necrosis rare. Other possible aspects are nuclear pseudoinclusions, cystic or myxoid changes, stromal sclerosis, calcification, and chronic inflammatory infiltrate [2, 13, 42, 43, 44, 45, 46, 47, 48, 49, 50]. Rarely, some tumors display a high mitotic rate, polymorphism, spindling, and xanthomatous changes [9].
Special stains, such as periodic acid-Schiff with diastase can highlight crystalloids, rod-like or rhomboid diastase-resistant membrane-bound intracytoplasmic crystalline formations originally noted by Masson [16] (Figure 1i—arrows). Ladanyi et al. were able to conclude that these are complexes of monocarboxylate transporter 1 (MCT1) interacting with a CD 147, a chaperone protein [51]. Their microscopic detection may be time-consuming and inconclusive. Some cases show simply a granular substance instead of crystals which could be a pre-crystalline formation of the MCTI-CD147 complex [51].
In electron microscopy, ASPS cells are poor in desmosomes and are lined by incomplete basement membranes in contact with capillaries [43, 47]. The cytoplasmic endoplasmic reticulum is as a rule sparse, mitochondria are numerous, and Golgi apparatus is greatly developed [43]. The latter is associated with crystalloids or pre-crystallized electron-dense granules mentioned above both of which are membrane-bound [31, 43, 47].
Immunostaining is, in most cases, unnecessary for diagnosis. Transcription factor TFE3 expression (Figure 1k) is linked to the gene fusion ASPL-TFE3 (Figure 2) but is not specific to ASPS as it can also be seen in subsets of epithelioid hemangioendotheliomas and PEComas [52], in granular cell tumor, malignant melanoma and pediatric renal cell carcinoma [53].
Fluorescent
This contrasts with sensitivity which is high (92%) Nevertheless, staining can also be weak or even absent in some cases, particularly in pre-analytically ill-prepared samples [54].
CD147/EMMPRIN, a glycoprotein of the immunoglobulin superfamily, is considered a marker of poor prognosis as well as for some authors a potential therapeutic target [54, 55]. Secreted by the cancer cells as a conjugate protein of MCT1, a lactate transporter, it induces matrix metalloproteinases production by neighboring stromal fibroblasts hence facilitating local tumor progression and ultimately metastasis [15, 54, 55]. Its expression is not limited to ASPS but has also been signaled in other lesions, such as granular cell tumor and clear cell renal cell carcinoma [54].
Diffuse cytoplasmic immunostaining with cathepsin K, a protease activated by the microphthalmia transcription factor (MITF) in osteoclasts, is fairly constant. But it is also seen in melanoma, clear cell sarcoma, granular cell tumor, and PEComa [56, 57].
Other possibly expressed markers with little significance in ASPS include desmin, actin [5, 6, 7, 8, 9, 10, 11, 12, 14], S-100 protein [21], NKIC3 [22], histiocytic marker CD68 KP1 [58], and vimentin [24]. Nuclear myogenin and MyoD1, cytokeratin, epithelial membrane antigen (EMA), chromogranin, synaptophysin, neurofilament, and glial fibrillary acidic protein (GFAP) are always negative [24, 47, 50]. The eventual clinical utility of standard immune complementary immunohistochemical tests in ASPS is yet to be determined. As mentioned earlier, lymphocytic infiltrate is rare. However, Goldberg et al. reported having identified activation of the PD-1 (programmed death-1) pathway with cell immunoreactivity for PD-L1 (PD-ligand 1) and individual CD8+ tumor-infiltrating T cells expressing PD-1 [59]. This, however, needs to be confirmed.
The unbalanced translocation der(17)t(X;17)(p11;q25) and its consequential fusion gene, a marker specific as well as sensitive [54], is the exhibited molecular label of ASPS. Cullinane et al. first reportedly identified this alteration cytogenetically [60]. This paved the way for the description of the two breakpoints on Xp11.2 and 17q25 [61] leading to the characterization of the two involved genes [14], the transcription factor TFE3 on Xp11.2 and a novel gene with no yet known function, ASPL/ASPSCR1 (alveolar soft part sarcoma locus/alveolar soft part sarcoma chromosomal region 1) on 17q25 (Figure 3a and b). In the encoded protein, there is conservation of the COOH-extremity and the DNA-binding domain of TFE3. Contrariwise its N-terminal sequences are occupied by ASPL which alters TFE3 normal activity. The oncoprotein then shifts to the nucleus where it behaves as a transcriptional driver.
Representations of TFE3 (a) and ASPL (b) genes with breakpoints indicated by arrows; bottom figures (c, d) correspond to the types 1 and 2 fusions respectively.
Two published cases show a reciprocal translocation however [14, 62]. Further, two mutually exclusive translocation variants have been identified although with no known clinical consequence at present. The ASPL gene has a unique breakpoint whereas the TFE3 gene possesses two possible breakpoints with two possible fusion types. According to Ladanyi et al., in type 1 fusion, the ASPL gene is joined in frame to TFE3 exon four (exon 3 is excluded). In type 2, it links with exon 3. Aulmann et al. [63] emphasized that under the later reference sequence (GenBank NM_006521) with a modified nomenclature (with no biological consequence) since Ladanyi’s publication [14], in type 1, the shortened ASPL gene (exons 1–7) joins directly with exon 6 of TFE3 (exon 5 is excluded) and in type 2 with exon 5 (Figure 3c and d).
Rapid diagnosis is usually achieved by fluorescent
The molecular mechanisms driven by the ASPL-TFE3 oncoprotein are not entirely known. Senescence promotion through p21 up-regulation wielding a mechanism of tumor progression by senescence-associated secretory phenotype (SASP) via proinflammatory cytokines secretion has been proposed [65, 66, 67, 68].
In gene expression profiling analysis, MET acts as a transcriptional target of the ASPL-TFE3 fusion. The latter binds to the activated promoter, induces MET tyrosine kinase autophosphorylation increasing MET protein expression in the presence of its ligand hepatocyte growth factor (HGF), and upregulates downstream signaling, to promote cell proliferation, growth, and invasion. MET appears to be a possible candidate for targeted therapy in [69, 70].
Other actions of TFE3 aim at targeting hypoxia-inducible factor (HIF-1a) which activates angiogenesis via factors, such as VEGFA, PDFG, or angiopoietin [32, 35, 71, 72, 73, 74], findings useful for antiangiogenic therapy investigations.
Further, melanoma inhibitor of apoptosis (ML-IAP), a factor of cell survival in melanoma targeted by MITF, is proven to be overexpressed in ASPS gene expression profiling [71, 75]. Both MITF and TFE3 are members of the basic helix–loop–helix leucine zipper transcription factors family and lock on to the same DNA motif, the E-box DNA consensus segment CANNTG [65, 76, 77].
CGH array studies show complex anomalies at multiple levels—gains of 1q, 8q, 16q, and Xp11-pter [78] with translocations, deletions, trisomy 12, trisomy 8, and loss of chromosome 17 after chemotherapy [79]. Updated results with high-resolution aCGH reported by Selvarajah et al. have confirmed these observations and suggested increased genomic instability in the metastatic setting with still more gains and losses [35].
Recent literature relative to immunogenicity in ASPS mentions significantly increased expression of host response factors to the lesion involving the innate activating receptors TLR2 and TLR9 [59].
In our experience, ASPS can have overlapping morphological features to some degree with other lesions of which the most frequent are listed in Table 1, but these mimics lack the specific recurrent nonreciprocal translocation found in ASPS. Key cytoarchitectural aspects, such as severe atypia, spindling, or pleomorphism generally are not in favor of ASPS. Moreover, the latter belongs to different clinical and immunohistochemical contexts. Generally, paragangliomas fit older patients [50] and are not readily observed in limbs. Unlike in ASPS, tumor cells are void of cytoplasmic glycogen. More importantly, they show neuroendocrine differentiation with the accompanying sustentacular cells being immunoreactive with anti-S-100 protein [57]. Clear cell sarcoma of soft tissue and metastatic melanoma consistently express melanocytic markers, such as HMB45 and Melan A, as well as S100 protein. Equivocally in metastatic melanoma, those antigens may be lost and like in ASPS, Cathepsin K can be immunopositive. Clear cell sarcoma of soft tissue may likewise express focally cathepsin K but harbors a reciprocal translocation t(12,22) resulting in the fusion of EWSR1-ATF1 in most cases [57]. Granular cell tumors, like in ASPS, may immunostain with TFE3 and cathepsin K but unlike ASPS they are also consistently reactive with anti-PS100, anti-SOX 10, and anti-inhibin antibodies [57, 80].
Clear cell sarcoma of soft tissue |
Metastatic melanoma |
Clear cell renal carcinoma |
Liver cell carcinoma |
Granular cell tumor |
PEComa |
Paraganglioma |
Rhabdomyosarcoma |
Some basic differential diagnoses of ASPS.
Renal cell carcinoma in children shares with ASPS the same fusion gene resulting from identical breakpoints [81, 82, 83] but here translocation is reciprocal. Reciprocity can be assessed using the right primers to the nonfunctional fusion site [72]. Contrary to ASPS, renal cell carcinomas immunostain with cytokeratin, epithelial membrane antigen (EMA), and PAX8 and do not express cathepsin K. They can harbor other fusion partners of TFE3, such as DVL2 and PRCC. These fusion genes, DVLE2-TFE3 and PRCC-TTF3 as well as the newly identified chimeric HNRNPH3-TTF3 have been detected in ASPS also [84].
Liver cell carcinoma can morphologically represent an important diagnostic pitfall, the liver being a possible primary site of ASPS. Hepatocarcinoma cells are immunopositive for hepatocyte paraffin 1 (Hep-Par1), glypican-3, and polyclonal carcinoembryonic antigen (P-CEA) [57].
Neuroendocrine or endocrine tumors, contrary to ASPS, stain with antibodies against chromogranin, synaptophysin, and CD56.
PEComas are most often located in the pelvis, gynecologic tract, and retroperitoneum. Like ASPS, a subset expresses TFE3 but with a double differentiation pattern, smooth muscle and melanocytic, staining with h-Caldesmon, HMB45, less often Melan A., all of which are negative in ASPS [85]. Adrenocortical carcinomas express Melan A or inhibin. Rhabdomyosarcomas are consistently positive for skeletal muscle differentiation markers (desmin, nuclear myogenin or MyoD1). A number of other lesions are perhaps not likely to be confused with ASPS but can nevertheless, because of their epithelioid cell morphology and abundant cytoplasm, be considered as differential diagnoses of the tumor in its less frequent solid appearance without alveolar configuration. These include epithelioid sarcoma, epithelioid angiosarcoma, epithelioid hemangioendothelioma, myoepithelioma, chordoma, meningioma, or even histiocytic sarcoma. But these present immunohistochemical and molecular profiles inconsistent with ASPS.
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',metaTitle:"Order and delivery",metaDescription:"Our books are published online and are accessible for free. However, if you are interested in ordering your hardcover copy, you can do so by contacting our Print Sales Department at orders@intechopen.com. All IntechOpen books are printed on demand in full-colour and delivered in signature packaging through free DHL Express delivery. A selection of our books in soft cover is also available through Amazon.",metaKeywords:null,canonicalURL:null,contentRaw:'[{"type":"htmlEditorComponent","content":"Our books are available hardcover, printed in full colour and produced to the highest standards on PEFC™ and FSC certified paper, complying with principles of responsible forestry worldwide. The paper size is 180 x 260 mm (7 x 10.2 inches).
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\\n\\nDiscounts available:
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\\n\\nWe currently accept the following payment options:
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\\n\\nIntechOpen will help you complete your payment safely and securely, keeping your personal, professional and financial information safe.
\\n\\nIn accordance with the best security practice, we do not accept card orders via email.
\\n\\nThe combined printing and delivery time for orders vary from 7-15 business days, depending on the printed quantity and destination. This period does not include any customs clearance difficulties that may arise and that are beyond our control. Once your order has been printed and shipped, you will receive a confirmation email that includes your DHL tracking number. You can then track your order at www.dhl.com.
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\\n\\nIntechOpen partners do not provide shipping service from Europe to the countries listed below. Please refrain from mailing items addressed to the countries listed below, until further notice.
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\n\nIntechOpen works with award winning print-houses and we hold to the fact that all of our printed products are of the highest quality.
\n\nIntechOpen books retail price range is:
\n\n100 - 159 GBP ex. VAT (available in USD and EUR)
\n\nDiscounts available:
\n\nBulk discounts are granted for orders of 10 copies and more.
\n\nThere is no minimum or maximum threshold on the quantity of book orders.
\n\nOrders have to be paid in advance and before printing. We accept payment in GBP, EUR and USD.
\n\nWe currently accept the following payment options:
\n\nWhen paying with a credit card, you will be redirected to the PayPal.com online payment portal.
\n\nIntechOpen will help you complete your payment safely and securely, keeping your personal, professional and financial information safe.
\n\nIn accordance with the best security practice, we do not accept card orders via email.
\n\nThe combined printing and delivery time for orders vary from 7-15 business days, depending on the printed quantity and destination. This period does not include any customs clearance difficulties that may arise and that are beyond our control. Once your order has been printed and shipped, you will receive a confirmation email that includes your DHL tracking number. You can then track your order at www.dhl.com.
\n\nIf you do not receive your order within 30 days from the date your order is shipped, please contact us to inquire about the shipping status at orders@intechopen.com.
\n\nTax: Residents of European Union countries need to add a Book Value-Added Tax Rate based on their country of residence. Institutions and companies, registered as VAT taxable entities in their own EU member state, will not pay VAT by providing IntechOpen with their VAT registration number. This is made possible by the EU reverse charge method.
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\n\nP.O. Boxes cannot be used as a Ship-To Address.
\n\nIntechOpen partners do not provide shipping service from Europe to the countries listed below. Please refrain from mailing items addressed to the countries listed below, until further notice.
\n\nWhen ordering our books from the countries listed below, please provide an alternative mailing address. For any further assistance, please contact us at orders@intechopen.com.
\n\nRestricted Ship-to Countries:
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\n\nRepresentative for: Germany, Austria, Switzerland
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Beloborodova",profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9731",title:"Oxidoreductase",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/9731.jpg",slug:"oxidoreductase",publishedDate:"February 17th 2021",editedByType:"Edited by",bookSignature:"Mahmoud Ahmed Mansour",hash:"852e6f862c85fc3adecdbaf822e64e6e",volumeInSeries:19,fullTitle:"Oxidoreductase",editors:[{id:"224662",title:"Prof.",name:"Mahmoud Ahmed",middleName:null,surname:"Mansour",slug:"mahmoud-ahmed-mansour",fullName:"Mahmoud Ahmed Mansour",profilePictureURL:"https://mts.intechopen.com/storage/users/224662/images/system/224662.jpg",institutionString:"King Saud bin Abdulaziz University for Health Sciences",institution:{name:"King Saud bin Abdulaziz University for Health Sciences",institutionURL:null,country:{name:"Saudi Arabia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9742",title:"Ubiquitin",subtitle:"Proteasome Pathway",coverURL:"https://cdn.intechopen.com/books/images_new/9742.jpg",slug:"ubiquitin-proteasome-pathway",publishedDate:"December 9th 2020",editedByType:"Edited by",bookSignature:"Xianquan Zhan",hash:"af6880d3a5571da1377ac8f6373b9e82",volumeInSeries:18,fullTitle:"Ubiquitin - Proteasome Pathway",editors:[{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",institutionURL:null,country:{name:"China"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9002",title:"Glutathione System and Oxidative Stress in Health and Disease",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/9002.jpg",slug:"glutathione-system-and-oxidative-stress-in-health-and-disease",publishedDate:"August 26th 2020",editedByType:"Edited by",bookSignature:"Margarete Dulce Bagatini",hash:"127defed0a50ad5ed92338dc96e1e10e",volumeInSeries:17,fullTitle:"Glutathione System and Oxidative Stress in Health and Disease",editors:[{id:"217850",title:"Dr.",name:"Margarete Dulce",middleName:null,surname:"Bagatini",slug:"margarete-dulce-bagatini",fullName:"Margarete Dulce Bagatini",profilePictureURL:"https://mts.intechopen.com/storage/users/217850/images/system/217850.jpeg",institutionString:"Universidade Federal da Fronteira Sul",institution:{name:"Universidade Federal da Fronteira Sul",institutionURL:null,country:{name:"Brazil"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Proteomics",value:18,count:3},{group:"subseries",caption:"Metabolism",value:17,count:6},{group:"subseries",caption:"Cell and Molecular Biology",value:14,count:8},{group:"subseries",caption:"Chemical Biology",value:15,count:10}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:3},{group:"publicationYear",caption:"2021",value:2021,count:7},{group:"publicationYear",caption:"2020",value:2020,count:12},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:2}],authors:{paginationCount:301,paginationItems:[{id:"116250",title:"Dr.",name:"Nima",middleName:null,surname:"Rezaei",slug:"nima-rezaei",fullName:"Nima Rezaei",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/116250/images/system/116250.jpg",biography:"Professor Nima Rezaei obtained an MD from Tehran University of Medical Sciences, Iran. He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. 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