Mechanical properties of steel in PSWC-BARs.
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These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\\n\\n\\n\\n\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\n\n\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"6132",leadTitle:null,fullTitle:"Advanced Casting Technologies",title:"Advanced Casting Technologies",subtitle:null,reviewType:"peer-reviewed",abstract:"Major casting processing advancements have been made in experimental and simulation areas. Newly developed advanced casting technologies allow foundry researchers to explore detailed phenomena associated with new casting process parameters helping to produce defect-free castings with good quality. Moreover, increased computational power allows foundry technologists to simulate advanced casting processes to reduce casting defects. In view of rapid expansion of knowledge and capability in the exciting field of casting technology, it is possible to develop new casting techniques. This book is intended to discuss many casting processing technologies. It is devoted to advanced casting processing technologies like ductile casting production and thermal analysis, casting of metal matrix composites by vortex stir casting technique, aluminum DC casting, evaporative casting process, and so on. This book entitled Advanced Casting Technologies has been organized into seven chapters and categorized into four sections. Section 1 discusses the production of ductile iron casting and thermal analysis. Section 2 depicts aluminum casting. Section 3 describes the casting manufacturing aspects of functionally graded materials and evaporative casting process. Section 4 explains about the vortex stir casting technique to process metal matrix composite castings. All the chapters discussed in detail the processing steps, process parameters involved in the individual casting technique, and also its applications. The goal of the book is to provide details on the recent casting technologies.",isbn:"978-1-78923-033-8",printIsbn:"978-1-78923-032-1",pdfIsbn:"978-1-83881-297-3",doi:"10.5772/intechopen.68254",price:119,priceEur:129,priceUsd:155,slug:"advanced-casting-technologies",numberOfPages:136,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"f2da423c1b74b321e5302adaaf888495",bookSignature:"T.R. Vijayaram",publishedDate:"May 2nd 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6132.jpg",numberOfDownloads:9803,numberOfWosCitations:31,numberOfCrossrefCitations:35,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:53,numberOfDimensionsCitationsByBook:1,hasAltmetrics:1,numberOfTotalCitations:119,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 28th 2017",dateEndSecondStepPublish:"April 18th 2017",dateEndThirdStepPublish:"November 19th 2017",dateEndFourthStepPublish:"December 19th 2017",dateEndFifthStepPublish:"February 19th 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"139338",title:"Prof.",name:"Thoguluva",middleName:"Raghavan",surname:"Vijayaram",slug:"thoguluva-vijayaram",fullName:"Thoguluva Vijayaram",profilePictureURL:"https://mts.intechopen.com/storage/users/139338/images/system/139338.jpg",biography:"Dr. T. R. Vijayaram is a senior professor in the Department of Mechanical Engineering, School of Mechanical Engineering, Bharath Institute of Higher Education and Research (BIHER), India. He is an expert in the field of materials and metallurgical, manufacturing, and mechanical engineering. He received his BE in Mechanical Engineering from Madurai Kamaraj University, India, followed by an ME in Industrial Metallurgy from PSG College of Technology, Bharathiyar University, India. He obtained his Ph.D. in Mechanical Engineering from Universiti Putra Malaysia. Later, he worked as a rector researcher in metallurgy at the Department of Chemistry and Industrial Chemistry (DCCI), Genoa University, Italy. His passion for academics, research, and education led him to obtain an MBA in Educational Management and an MA in Sociology from the University of Madras, India. He is also a Chartered Engineer (India) and a member of several professional and scientific bodies in India and abroad, including the Indian Society for Technical Education (ISTE), Institution of Engineers (IEI), Institute of Indian Foundryman (IIF), and Society of Automotive Engineers (SAE). He is also a fellow of IEI. Dr. Vijayaram received the Distinguished Scientist Award in Metallurgical and Materials Engineering for his outstanding contribution to metallurgy. He has published more than 210 papers in international and national journals, conferences, broadsheets, and magazines. His areas of research include materials engineering, metallurgical engineering, manufacturing engineering, and mechanical engineering.",institutionString:"Bharath University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"944",title:"Metallurgy",slug:"metals-and-nonmetals-metallurgy"}],chapters:[{id:"57999",title:"Thin Wall Ductile Iron Castings",doi:"10.5772/intechopen.72117",slug:"thin-wall-ductile-iron-castings",totalDownloads:1023,totalCrossrefCites:2,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The use of austempered ductile iron (ADI) as an alternative material has increased, and it is predicted that it will reach 300,000 tons by the year of 2020 due to its characteristics especially design flexibility. When the reduction in weight is considered as a parameter for energy saving, ADI is presented as thin wall austempered ductile iron (TWADI). To produce a good quality TWADI, a good quality thin wall ductile iron (TWDI) must be used as a raw material. Good quality TWDI is produced by casting design. This chapter discusses the production of thin wall ductile iron, including its characterisation and defect. The discussion includes the background of thin wall casting (TWC) and TWDI, applying TWC in general casting, the problems in producing TWDI, characterisation of the TWDI and specific defects.",signatures:"Rianti Dewi Sulamet-Ariobimo, Johny Wahyuadi Soedarsono and\nTresna Priyana Soemardi",downloadPdfUrl:"/chapter/pdf-download/57999",previewPdfUrl:"/chapter/pdf-preview/57999",authors:[{id:"208291",title:"Dr.",name:"Rianti",surname:"Sulamet-Ariobimo",slug:"rianti-sulamet-ariobimo",fullName:"Rianti Sulamet-Ariobimo"}],corrections:null},{id:"57825",title:"Thermal Analysis of Ductile Iron Casting",doi:"10.5772/intechopen.72030",slug:"thermal-analysis-of-ductile-iron-casting",totalDownloads:1564,totalCrossrefCites:3,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Pure metals solidify with a solidification front that is very well defined and a clearly delineated solid-liquid interface. Ductile cast iron solidification is characterised by a very thin solidified skin and appearance of different phases. The outer skin is formed being very thin in ductile iron; the expansion occurs due to graphite nucleation into the casting forces to the mould walls. With proper care taken while designing and during melt processing stage, quality ductile iron castings can be produced with minimal risering. With recent developments in sensing and storing instruments, it is now possible to see and measure structural transformations within the solidification in ductile iron castings very precisely. The shape of a cooling curve measured by a thermocouple mounted on a thermal analysis sample cup reflects the solidification process of the melted cast alloy for the given solidification conditions. By analysing particular cooling curve, the solidification start, eutectic arrests, recalescence, amount of undercooling and end of freezing temperature temperatures are generated. The thermal analysis data so generated will be used to study composition, soundness, chill and microstructure by analysis of cooling curve. The cooling rates measured in degrees per second at different stages of solidification sequence will be analysed and correlated with the properties of the castings to be produced from the same melt.",signatures:"Vasudev D. Shinde",downloadPdfUrl:"/chapter/pdf-download/57825",previewPdfUrl:"/chapter/pdf-preview/57825",authors:[{id:"208778",title:"Prof.",name:"Vasudev",surname:"Shinde",slug:"vasudev-shinde",fullName:"Vasudev Shinde"}],corrections:null},{id:"57796",title:"Depicting Aluminium DC Casting by Means of Dimensionless Numbers",doi:"10.5772/intechopen.71893",slug:"depicting-aluminium-dc-casting-by-means-of-dimensionless-numbers",totalDownloads:1141,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"DC casting of aluminium and its alloys is a controlled heat removal solidification process. The rate of heat extraction has strong effects on the microstructure and mechanical properties of the solidified alloy ingots. In view of this strict temperature, control over the ingot as it solidifies should be implemented in order to achieve metal with the best possible properties. In situ direct temperature measurements are complicated; so in this report, the use of dimensionless analysis to predict temperature distributions on the ingots as they are casted is proposed. It is reported that the dimensionless groups that better represent the impact of process variables on the solidification of aluminium and its alloys are the Péclet (Pe) and Biot (Bi) numbers.",signatures:"José C. Méndez, Ricardo R. Ambriz, David Jaramillo and Gabriel\nPlascencia",downloadPdfUrl:"/chapter/pdf-download/57796",previewPdfUrl:"/chapter/pdf-preview/57796",authors:[{id:"46960",title:"Prof.",name:"Gabriel",surname:"Plascencia",slug:"gabriel-plascencia",fullName:"Gabriel Plascencia"},{id:"85573",title:"Dr.",name:"Ricardo Rafael",surname:"Ambriz",slug:"ricardo-rafael-ambriz",fullName:"Ricardo Rafael Ambriz"},{id:"170247",title:"Dr.",name:"David",surname:"Jaramillo",slug:"david-jaramillo",fullName:"David Jaramillo"},{id:"208155",title:"Prof.",name:"Claudio",surname:"Méndez",slug:"claudio-mendez",fullName:"Claudio Méndez"}],corrections:null},{id:"58487",title:"Castability and Characteristics of High Cerium Aluminum Alloys",doi:"10.5772/intechopen.72830",slug:"castability-and-characteristics-of-high-cerium-aluminum-alloys",totalDownloads:1010,totalCrossrefCites:6,totalDimensionsCites:13,hasAltmetrics:0,abstract:"This chapter describes the development and the castability of near eutectic aluminum-cerium (Al-Ce) alloy systems. These alloys have good mechanical properties at high temperatures and are very castable. The castability of the binary systems is as good or better than the aluminum-silicon system with some deterioration as additional alloying elements are added. In alloy systems that use cerium in combination with common aluminum alloying elements such as silicon, magnesium, and/or copper, the casting characteristics are generally better than the aluminum-copper system. Alloying with magnesium increases room temperature strength considerably.",signatures:"David Weiss",downloadPdfUrl:"/chapter/pdf-download/58487",previewPdfUrl:"/chapter/pdf-preview/58487",authors:[{id:"206168",title:"Mr.",name:"David",surname:"Weiss",slug:"david-weiss",fullName:"David Weiss"}],corrections:null},{id:"57524",title:"Casting and Applications of Functionally Graded Metal Matrix Composites",doi:"10.5772/intechopen.71225",slug:"casting-and-applications-of-functionally-graded-metal-matrix-composites",totalDownloads:1502,totalCrossrefCites:3,totalDimensionsCites:6,hasAltmetrics:0,abstract:"This chapter discusses the concepts, casting techniques and applications of functionally graded materials metal matrix composites (FGMMCs). Considerations were given to bulk functionally graded aluminium matrix composites (FGAACs) production processes. Liquid-metal forging processes of FGAACs fabrication, such as infiltration process, squeeze casting, friction casting or compocasting, stir, and centrifugal casting were discussed. The chapter provides basic concepts of the processes and overview of their processing parameters, such as mould rotational speed; reinforcement particles size and volume; degassing method; melting and pouring temperatures; pressure; and stirrer. The study notes that functionally graded materials (FGMs) are commonly used in automotive, aircraft, aviation, chemical, medical, engineering, renewable energy, nuclear energy, and optics electronics industries.",signatures:"Williams S. Ebhota and Tien-Chen Jen",downloadPdfUrl:"/chapter/pdf-download/57524",previewPdfUrl:"/chapter/pdf-preview/57524",authors:[{id:"206268",title:"Dr.",name:"Williams",surname:"Ebhota",slug:"williams-ebhota",fullName:"Williams Ebhota"},{id:"214786",title:"Prof.",name:"Tien-Chien",surname:"Jen",slug:"tien-chien-jen",fullName:"Tien-Chien Jen"}],corrections:null},{id:"59140",title:"Evaporative Pattern Casting (EPC) Process",doi:"10.5772/intechopen.73526",slug:"evaporative-pattern-casting-epc-process",totalDownloads:1235,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The chapter provides details of operations and activities in evaporative pattern casting (EPC) Process. The process was developed in the year 1956 to tackle some of the inadequacies of the traditional sand casting processes but has in itself some challenges that should be taken care of if sound castings would be obtained. The challenges come mainly from the evaporative pattern employed as pattern material in the process. The material makes the process to be sensitive to process variables such that proper and adequate control should be ensured to have castings of sound integrity. Some of the known process variables are pouring temperature, refractory coating, vibration and pattern and molding materials. In the whole the EPC is known to have edge over the traditional sand casting methods.",signatures:"Babatunde Victor Omidiji",downloadPdfUrl:"/chapter/pdf-download/59140",previewPdfUrl:"/chapter/pdf-preview/59140",authors:[{id:"228410",title:"Dr.",name:"Victor",surname:"Omidiji",slug:"victor-omidiji",fullName:"Victor Omidiji"}],corrections:null},{id:"58816",title:"Fabrication of Aluminum Matrix Composites by Stir Casting Technique and Stirring Process Parameters Optimization",doi:"10.5772/intechopen.73485",slug:"fabrication-of-aluminum-matrix-composites-by-stir-casting-technique-and-stirring-process-parameters-",totalDownloads:2330,totalCrossrefCites:21,totalDimensionsCites:30,hasAltmetrics:1,abstract:"Aluminum matrix composites (AMCs) and hybrid aluminum matrix composites (HAMCs) becomes choice for automobile and aerospace industries due to its tunable mechanical properties such as very high strength to weight ratio, superior wear resistance, greater stiffness, better fatigue resistance, controlled co-efficient of thermal expansion and good stability at elevated temperature. Stir casting is an appropriate method for composite fabrication and widely used industrial fabrication of AMCs and HAMCs due to flexibility, cost-effectiveness and best suitable for mass production. Distribution of the reinforcement particles in the final prepared composite regulates the anticipated properties of AMCs and HAMCs. However, distribution of reinforcements is governed by stirring process parameters. The study of effect of stirring parameters in the particle distribution and optimal selection of these is still a challenge for the ever-growing industries and research. In this chapter accurate and precise attempts were taken to explore the effect of stirring parameters in stir casting process rigorously. Further, Optimal values of stirring parameters were suggested which may be helpful for the researchers for the development of AMCs and HAMCs. This chapter may also provide a better vision towards the selection of stirring parameters for industrial production of AMCs and HAMCs comprising superior mechanical properties.",signatures:"Mohit Kumar Sahu and Raj Kumar Sahu",downloadPdfUrl:"/chapter/pdf-download/58816",previewPdfUrl:"/chapter/pdf-preview/58816",authors:[{id:"200118",title:"Dr.",name:"Raj",surname:"Sahu",slug:"raj-sahu",fullName:"Raj Sahu"},{id:"225730",title:"Mr.",name:"Mohit",surname:"Sahu",slug:"mohit-sahu",fullName:"Mohit Sahu"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"3817",title:"Developments in Corrosion Protection",subtitle:null,isOpenForSubmission:!1,hash:"8ff86fac7ac8bce142fdc3c0e5a79f30",slug:"developments-in-corrosion-protection",bookSignature:"M. 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Reinforced concrete is the number one medium of construction, in which reinforcing bar (rebar) is one of the two component elements; the other element being concrete.
\nIt was in the mid-nineteenth century when builders in different countries experimented with concrete, reinforced with steel elements of different types.
\nEasy availability of the component materials, easy formability, rigidity, strength, safety and durability of reinforced concrete construction made more and more people interested in such constructions.
\nPlain round bars of mild steel became the standard rebar.
\nThe time-dependent performance of concrete structures, reinforced with such bars, set the standards of performance in the context of durability.
\nBesides the external elements, e.g., water/moisture, oxygen, carbon dioxide, chlorides, sulphates, alkalis, and other deleterious materials, which can have destabilizing effects on concrete constructions, it cannot be overlooked that the intrinsic properties of the two principal constituent materials, viz., concrete and rebars, have much to do with durability of reinforced concrete; Kar [1].
\nBesides concrete and rebar, “bond” between concrete and rebar, though not a material by itself, and though no one buys it or pays for it like they buy or pay for concrete and rebar, is a property that is no less important than concrete and rebar are in the context of reinforced concrete construction.
\nVery little consideration has been given to what leads to good “bond”, and what can prevent “bond” between concrete and reinforcing elements. Also important can be the selection of an appropriate percent elongation, better still, ductility, of the material of the rebar.
\nIn the context of “bond” and its influence on the performance of reinforced concrete, Kar [2] has suggested three terms, viz., “bond”, “effective bond” and “engagement”. While the last two are synonymous, that cannot be said of “bond”.
\nKar [2] has shown that the quality of “engagement” between rebar and concrete can greatly influence the performance of reinforced concrete elements and structures.
\nBuoyed by the performance of reinforced concrete, with plain round bars as rebars, engineers thought of making reinforced concrete constructions more economical by using rebars of higher strength steel.
\nGradually, many different types of round reinforcing bars were introduced; Abrams [3].
\nForgetful of earlier unsatisfactory experiences in the nineteenth and early twentieth century with bars, having different types of protrusions on the surface, engineers decided that the use of high strength steel would be possible by increasing the bond between rebar and concrete by providing ribs on the surface of such rebars.
\nPlain round bars of mild steel thus gave way to rebars of high strength steel wherein the bars are characterized by the presence of ribs on the surface (\nFigures 1\n and \n2\n). Ribbed bars were introduced in the belief that ribbed surfaces would increase bond between rebars and concrete.
\nTypical cold twisted deformed (CTD) rebar, with lugs and protrusions on the surface and stresses beyond yield on the entire body, which replaced plain round bars starting the decade of the 1960’s.
Typical high strength TMT rebars with surface deformations, which replaced plain round bars starting the decade of the 1960’s.
The provision of ribs on the surface of rebars of high strength steel was facilitated in 1947 by ASTM International [4] publishing ASTM A305, that provided Specifications on rebar deformation patterns.
\nContrary to the beliefs and expectations that (a) the presence of ribs on the surface of rebars of steel would increase the “bond” between rebars and the surrounding concrete, and (b) there would be no detrimental effect of the ribs on the performance of concrete constructions, which may be reinforced with ribbed rebars, the presence of ribs on the surface of rebars may create void spaces, at isolated locations, between rebars and concrete, thereby decreasing “bond”. However, the wedge action of ribs, together with the reduced “bond”, may (or may not) lead to an increase in the “engagement” between rebars and concrete.
\nNo thought was spared as to the likely consequences the use of bars, with surface deformations or ribs, could have on the long term performance, or even on the immediate performance and load-carrying capacities of reinforced concrete constructions; Kar [1, 2, 5].
\nEngineers and manufacturers of rebars blindly followed the lead of ASTM International. The Bureau of Indian Standards (BIS) in India published the Standard IS 1786 on High Strength Deformed Steel bars and Wires for Concrete Reinforcement --- Specification [6].
\nThough plain round bars, as in IS 432 (Part I) [7], and Grade A bars in IS 2062 [8] were available, gradually plain round bars gave way to ribbed bars where the strength of steel in rebars was increased artificially by twisting the bars beyond yield at a cold state, giving rise to CTD bars (\nFigure 1\n).
\nWith time, manufacturers of rebars in India and elsewhere adopted the technique of increasing strength through the centuries-old practice of quenching, couched in diplomatic language as thermomechanical treatment, giving rise to TMT bars (\nFigure 2\n).
\nDuring the last sixty years or so, almost all reinforced concrete constructions worldwide have been with ribbed rebars of high strength steel, whether of the CTD or TMT type or not.
\nThe time-dependent performances of concrete structures (\nFigures 3\n–\n5\n), reinforced with these later day rebars, failed to match the time-dependent performance of concrete structures, which were reinforced with plain round bars of mild steel.
\nDistress in staging of overhead water reservoir due to corrosion in rebars.
Abandoned hospital building a decade after construction in the new township of Salt Lake City, Kolkata.
Typical distress in ground level columns caused by rust in ribbed TMT bars in a 10 year old building in Kolkata.
The relatively poor performance of concrete structures since the introduction of high strength rebars, with surface deformations, has caused worldwide concern.
\nThere had to be reasons, and the reasons were not unknown; Alekseev [9, 10], and Kar [1, 5, 11, 12, 13, 14, 15, 16, 17]. But engineers and manufacturers of rebars paid no heed.
\nThe rebars, with surface deformations, are today covered by the Indian Standard IS 1786 [6] for high strength deformed steel bars. The Standard covers both CTD and TMT bars. ASTM International in the USA published quite a few Specifications on ribbed rebars of high strength steel. The most commonly used rebars are covered in ASTM A615/A615M [18].
\nIn terms of durability, the structures may be adversely affected because of the inability of concrete to stand up to the external elements, e.g., chlorides, sulphastes, etc. or even to water as its presence may permit alkali-silica reaction in concrete in certain cases.
\nMost often, the durability of concrete constructions is adversely affected by corrosion in the steel rebars in the case of reinforced concrete (\nFigures 3\n\n–\n\n6(h)\n and \n(i)\n), and by corrosion in the wires and strands of steel in the case of prestressed concrete.
\nA collection of plain bars free from rust and ribbed CTD and TMT bars with various stages of corrosion.
Though less frequent, corrosion in ribbed rebars (\nFigure 2\n), used as secondary reinforcement in prestressed concrete constructions, can trigger unacceptable conditions of distress in prestressed concrete constructions.
\nThe focus here is on rebars and durability of reinforced concrete constructions, as influenced by rebars.
\nFollowing the use of ribbed bars of high strength steel, the world has seen a significant fall in the long term performance of reinforced concrete constructions. Sights of decay and distress in concrete constructions, reinforced with ribbed rebars of steel, became inescapable (\nFigures 3\n–\n5\n) within years of their construction.
\nA 1999 survey of bridges and buildings of reinforced concrete construction in the public domain in and around Kolkata, India revealed that while none of the structures, built since the 1940s with plain round bars of mild steel, showed any sign of distress, all the structures built with ribbed bars (\nFigure 1\n) in the 1970s and 1980s were showing signs of distress; Kar [11].
\nIn a 1991 article in ACI Materials Journal, American Concrete Institute, Papadakis, Vayenas and Fardis [19] wrote: “The last two decades have seen a disconcerting increase in examples of the unsatisfactory durability of concrete structures, specially reinforced concrete ones.”
\nSixteen years later in 2007, Swamy [20] from UK was more forthright in his expression when he wrote in the Indian Concrete Journal: “The most direct and unquestionable evidence of the last two/three decades on the service life performance of our constructions and the resulting challenge that confronts us is the alarming and unacceptable rate at which our infrastructure systems all over the world are suffering from deterioration when exposed to real environments.”
\nAn analysis of the observations by Papadakis et al. [19], by Swamy [20] and by others leads to the recognition that the relatively poor performance of reinforced concrete constructions followed the start of use of ribbed rebars of high strength steel.
\n\n\nFigure 5\n shows typical conditions of concrete columns, reinforced with ribbed rebars (\nFigure 2\n), ten years after the construction of a building in Kolkata. All the columns at the ground level of the building suffered a similar fate.
\nThe findings of the 1999 survey as well as the structures in \nFigures 3\n–\n5\n show clearly that compared to concrete structures, reinforced with plain round bars of mild steel, concrete structures, reinforced with ribbed bars of medium strength and high strength steel, reach states of distress much earlier.
\nThis excessive corrosion in ribbed rebars of carbon steel suggests that the susceptibility of ribbed rebars to corrosion at accelerated rates is an intrinsic nature of ribbed rebars of carbon steel.
\nHowever, there had been hesitation by engineers in recognizing that today’s ribbed bars were highly susceptible to corrosion at accelerated rates, and this excessive corrosion in today’s rebars is due to.
the damages caused to the ribs at the time of provision of ribs on the surface
the damages caused to the ribs at the time of transportation and handling of rebars
the presence of ribs on the surface of today’s rebars.
The hesitation to recognize ribs as a principal cause of excessive corrosion in rebars led not only to the continued condemnation of all new reinforced concrete constructions to early decay, distress and failure, but also to ASTM International, BIS and such other organizations publishing multiple Specifications/Standards on rebars as imagined solutions to the problem of early distress in reinforced concrete constructions, e.g., ASTM International publishing A775 [21] for epoxy coated ribbed bars, and on its failure to solve the problem, ASTM International A955/A955M for Deformed and Plain Stainless Steel Bars [22], and when that did not work, ASTM International published A1055 [23] for zinc (first coat) and epoxy (2nd coat), which too has serious limitations, as epoxy coating prevents the all-important “bond” with concrete (\nFigures 7\n and \n8\n).
\nConcrete easily separates from epoxy coated rebars under vibratory loading conditions whereas all structures are required to resist vibratory loads due to earthquakes; separation led to failure of buildings.
The bond between epoxy coated rebar and concrete will be negligible, as seen in a column; the ribs on the surface of rebars engage the concrete up to a limit and that too when the loading is monotonous; absence of bond led to lower load-carrying capacity.
The lack of “bond” can have serious consequences: (a) cracks in structures (\nFigure 6(g)\n), (b) lowered load carrying capacities (Kar [2]), and (c) chunks of concrete falling (\nFigure 9\n) or even structures collapsing (\nFigure 7\n).
\nA view of the deck of the Jogeswari flyover in Mumbai seven years after construction; concrete separated from rebars with poor bond qualities.
Like epoxy coated bars, stainless steel bars too fail to solve the problem, as ribbed bars of stainless steel too may corrode under conditions of exposure of concrete structures to chlorides, and additionally such bars may not bond or may not bond well with concrete.
\nFailing to recognize that the problem of early distress in today’s reinforced concrete constructions is due to the use of ribbed rebars of steel as in the Indian Standard IS 1786 [6], BIS published the Indian Standard IS 13620 [24] for Fusion Bonded Epoxy Coated Reinforcing bars.
\nJust as BIS failed to recognize that the problem of early distress in reinforced concrete constructions started with the use of ribbed bars as in IS 1786, BIS also failed to recognize that, as cautioned in SubSection 5.6.1 of its Standard IS 456 [25], epoxy coated bars would not bond with the surrounding concrete, whereas the availability of the required “bond” is an essential requirement for reinforced concrete.
\nSimilarly, as ASTM International published Specifications on epoxy coated bars and stainless steel bars, without a recognition or understanding of the basic cause(s) of early distress in reinforced concrete constructions of recent decades, and the significance of “bond” between rebars and the surrounding concrete, BIS in India followed suit by publishing the Indian Standard IS 16651:2017 on High Strength Deformed Stainless Steel bars and Wires for Concrete Reinforcement Specification [26].
\nThe story is the same in many other countries.
\nIt is recognized here that:
corrosion in rebars is greatly influenced by the intrinsic nature of the particular rebars; e.g., stainless steel bars will not generally corrode whereas mild steel and medium tensile steel bars will corrode, and high tensile strength steel bars with higher carbon contents will corrode more and at faster rates
the surface conditions/features on the rebar influence the rate of corrosion; the provision and the presence of ribs, as in bars conforming to IS 1786 [6] and ASTM A615/A615M [18] lead to acceleration in the rate of corrosion; Alekseev [9, 10], and Kar [1, 5, 12]
the manufacturing process influences the rate of corrosion; by stretching/stressing the bars beyond yield, the CTD process leads to corrosion at accelerated rates; the TMT process too hastens corrosion due to stresses from quenching effort; Alekseev [9, 10], and Kar [1, 5, 11, 12].
It has been recognized earlier that the problem of early distress in reinforced concrete structures started showing up following the start of use of steel reinforcing bars with ribs on the surface.
\n\n\nFigure 6(d)\n shows the start of corrosion at the ribs of TMT bars.
\n\n\nFigure 6(c)\n shows corrosion all over the surface of relatively fresh ribbed TMT bars.
\nThe four bottom bars in \nFigure 6(b)\n show the start of corrosion preferentially at the ribs of untwisted ribbed bars while the four top bars show corrosion all over the surface of the ribbed bars as a consequence of stressing the bars beyond yield.
\nThese show that:
the provision and presence of ribs invite corrosion
high stresses, specially stresses beyond yield, lead to corrosion at accelerated rates.
It cannot be overlooked that the ribs were provided out of a perceived necessity of improved “bond” between rebar and concrete when the rebars were upgraded from low-carbon to medium carbon or high carbon steel for higher strength. The truth is that the presence of ribs on the surface of rebars decreases “bond” between rebars and concrete. But the ribs may provide greater resistance to longitudinal movement of the bars relative to the surrounding concrete. Also, as found in the preceding, the ribs encourage corrosion in rebars; Alekseev [9] and Kar [1, 5].
\nWhether of the CTD or TMT type, or not, the reasons for ribbed bars of carbon steel being intrinsically susceptible to corrosion at accelerated rates are:
residual stresses develop at the bases of ribs during the manufacturing stage
cracks or surface damages, which trigger corrosion, may develop at the ribs at the time of manufacture, during transportation and handling
nominal stresses in ribbed rebars under load are enhanced in keeping with the phenomenon of stress concentration due to the presence of ribs or cracks
additional stresses develop in ribs in a loaded structure due to the wedge action of such ribs against surrounding concrete
the sum-total of stresses and strains in Items 1 to 4 approach or reach yield stress or strain levels
the rate of corrosion increases with increasing stress levels; the rate accelerates as the stress or strain approaches yield levels, and the surface becomes unstable once at or beyond yield, whereupon the bars become incapable of being passivated and consequently the process of corrosion becomes unstoppable; Kar [1].
The CTD and TMT processes are in violation of the inherent nature of steel to be ductile and to protect itself; Kar [1].
\nThese CTD and TMT bars of high strength steel have another shortcoming to contend with: “The effect of stresses on corrosion is reflected more distinctly in the mechanical characteristics of the reinforcement, specially of high-strength steels with low ductility.” [[10], pp. 203–204].
\nOn the basis of extensive work in Russia, Alekseev [10] commented on the above scenario thus: “the durability of reinforcement specimens with a stepped (deformed) profile may be roughly an order less than that of smooth specimens since the former have stress concentrators on the surface at the bases of projections, which represent sites of preferential formation of cracks.” [[10], pp. 221–222].
\nThe preceding explains the reasons behind the intrinsic susceptibility of ribbed bars of steel to corrosion at accelerated rates.
\nIt is the effect of this high susceptibility of ribbed bars to corrosion that led to the observations by Papadakis et al. [19] and Swamy [20], and to the types of early distress in reinforced concrete constructions, as depicted in \nFigures 3\n–\n5\n.
\nIt has been recognized that rebars with surface deformations corrode excessively, leading to concrete constructions with such rebars reaching states of distress early.
\nThe obvious solution to the problem would have been to use plain round bars as in the past. But engineers, having used in design and construction rebars of medium strength and high strength steel over the decades, would not like to go back to the use of rebars of steel having yield strength of 40 to 50 percent of the yield strength of steel in today’s rebars.
\nTwo options are available.
\n\n
In recognition of the fact that the problem of early distress, cited in the preceding, resulted primarily from a combination of two factors:
extra susceptibility (compared to that of plain round bars of mild steel) of ribbed bars, high yield strength deformed bars, and ribbed CTD and TMT bars to corrosion
availability of a moist environment inside concrete
The concept of making concrete structures durable through surface protection in the nature of waterproofing treatment is gradually gaining ground in the USA and in other countries, and BIS, in recognition that concrete constructions with ribbed bars, as in IS 1786 [6], required extra protection against corrosion in the rebars, made waterproofing treatments a requirement for durability. SubSection 8.2.1 of IS 456:2000 [25] partly reads: “The life of the structure can be lengthened by providing extra cover to steel, by chamfering the corners or by using circular cross-section or by using surface coatings which prevent or reduce the ingress of water, carbon dioxide or aggressive chemicals.”
\nIt needs to be noted here that the provision of waterproofing treatments to concrete structures became essential because of the failure of the ribbed CTD and TMT bars, conforming to IS 1786 in India, ASTM A615/A615M [18] in the USA or bars conforming to similar other Standards/Specifications in other countries, to make concrete structures as durable as those used to be when the rebars had plain surfaces, and high strengths in the rebar materials were not achieved through the highly detrimental processes of cold twisting beyond yield as in the case of CTD bars (\nFigure 6(b)\n) or through quenching/thermal hardening/thermomechanical treatment as in the case of TMT bars (\nFigure 6(c)\n and \n(d)\n).
\nKar’s [16, 27, 28] art of making reinforced concrete structures durable through the provision of waterproofing treatment on the surface of such structures is an indirect way of solving the problem that was or that is invited with the use of the potentially damaging ribbed rebars of high strength steel, that was encouraged by ASTM International, BIS, ISO and such other organizations, which recommended and permitted the use of ribbed rebars, with or without the added processes of (a) cold twisting, as in CTD bars, or (b) quenching as in TMT bars, in the false belief or hope that concrete structures, reinforced with such bars, would be at least as durable as concrete structures of earlier era, which were reinforced with plain round bars of mild steel.
\nThough surface protection systems have worked pretty well, it does have the following shortcomings:
this additional treatment requires additional project time and expenditure
the materials used, and the specifications followed, may not be appropriate
there can be shortcomings in workmanship
such external treatments may be damaged or may have limited life spans, requiring repeat treatment
it does not solve the problem of excessive corrosion on the surface of rebars prior to concreting (\nFigure 6(c)\n and \n(f)\n), leading to reduction or total loss of bond between rusted rebars and concrete whereas the availability of competent “bond” between rebars and the surrounding concrete is a pre-requisite for successful performance of reinforced concrete construction.
In spite of these shortcomings, it is essential that all concrete structures, reinforced with ribbed rebars of steel, as in IS 1786 [6], ASTM A305 [4] or conforming to other Standards, be provided with surface protection in the nature of waterproofing treatment; Kar [12, 13, 16, 27, 28].
\n\n
A better solution to the problem of early distress in reinforced concrete constructions with conventional rebars of medium strength and high strength steel would be to use plain round bars as it used to be before the 1960s or 1970s.
\nThat would have solved the problem of excessive corrosion in rebars, and that would have made reinforced concrete constructions as durable as such constructions used to be in the past.
\nBut the problem is that the requirement of much longer development/anchor length might not have permitted the use of plain round bars of medium strength and high strength steel.
\nWith the innovative concept of PSWC-BAR, Kar [14] provided a direct solution (at no added effort or cost) to the problem of early distress in concrete constructions with ribbed rebars of high strength carbon steel. PSWC-BAR was initially named as C-bar.
\nKar [5] explained why PSWC-BAR is the most ideal rebar for reinforced concrete constructions.
\nThe use of PSWC-BAR, at no added effort or cost, not only solves the problem of early distress in reinforced concrete constructions through several-fold enhancement of life span of such constructions, it also enhances several fold the ductility and energy-absorbing capacity of reinforced concrete constructions; Kar [2].
\nThe several-fold enhancement of life span, at no added effort or cost, has the effect of lowering the life cycle cost of reinforced concrete construction to a fraction of what it is today.
\nThe use of PSWC-BAR increases load-carrying capacities of reinforced concrete elements, and through the several-fold enhancement of life span, the use of PSWC-BAR minimizes the harmful effects of construction on the environment and the global climate through considerable lowering of the need for the manufacture of cement, steel, etc. Kar [29].
\n\n
PSWC-BAR of steel, characterized by plain surface and gentle wave-type configuration
PSWC-BAR, because of the absence of ribs or any other special surface feature, if made of the same steel, will not corrode more than conventional plain round bars would do.
\nPSWC-BAR, because of its gentle wave-type configuration, enhances “effective bond”, i.e., “engagement” between rebar and concrete; Kar [2]. Tests on beams and columns at different universities have shown that, among all types of rebars, PSWC-BAR, with its wave-type configuration, provides the best “engagement” between rebar and concrete, leading to significant enhancement of the various positive attributes of reinforced concrete; Kar [2, 17, 30, 31] and Varu [32].
\nWhile the test for loose rust and bond, or say, loss of bond, may lead to disqualification of most or all ribbed bars, conforming to IS 1786, and such other Standards, numerous tests on beams and columns have consistently shown that among rebars of steel, the use of PSWC-BAR, free from the ill effects of ribs, and if manufactured as Grade A of Hot Rolled Medium and High Tensile Structural Steel, as in IS 2062 [8], or conforming to appropriate Standards for plain round bars, can lead to the best load-carrying capacities, ductility and energy-absorbing capacity; Kar [2], indicating thereby that the “effective bond” is the best in the case of PSWC-BARs.
\nBesides these big fundamental differences between today’s ribbed bars, as in IS 1786, and PSWC-BARs (\nFigure 10\n) as in IS 2062 [8], there lies the undisputedly stark difference between the very poor time-dependent performances (durability) of concrete structures, reinforced with ribbed bars, as in IS 1786 [6], ASTM A615/A615M [18] and such other Standards/Specifications elsewhere and the time-dependent performances of concrete structures, reinforced with hot rolled plain round bars with wave-type configuration, which are characteristic of PSWC-BARs.
\nThere are various other advantages of using PSWC-BAR as rebars in reinforced concrete construction. A comparison of the load–displacement plots in \nFigure 11(a)\n and \n(b)\n show clearly that:
because of several fold higher ductility and energy-absorbing capacity, the use of PSWC-BARs as rebars has the potential to prevent structural failures and catastrophes during earthquakes
because of several times higher deflection (displacement) of flexural elements, there can be visible warnings before failure, thereby saving lives.
load-carrying capacities of reinforced concrete elements increase when PSWC-BARs are used.
Ductile response of beam reinforced with PSWC
Recommended mechanical properties of PSWC-BAR for durable and earthquake resistant concrete constructions are provided in \nTable 1\n.
\nSl. No. (1) | \nProperty (2) | \nFe 415 (3) | \nFe 500 (4) | \nFe 550 (5) | \n
---|---|---|---|---|
i) | \nyield stress | \n415.0 | \n500.0 | \n550.0 | \n
ii) | \nyield stress | \n500.0 | \n600.0 | \n660.0 | \n
iii) | \nY/Yspecified ratio1\n | \n1.02–1.2 | \n1.02–1.2 | \n1.02–1.2 | \n
iv) | \nTS/ Yspecified ratio2\n | \n≥ 1.15 - ≤ 1.40 | \n≥ 1.15 - ≤ 1.40 | \n≥ 1.15 - ≤ 1.40 | \n
v) | \nElongation, percent, | \n20.0 | \n16.0 | \n12.0 | \n
Mechanical properties of steel in PSWC-BARs.
Note: 1) Y/Y specified ratio refers to ratio of actual yield strength to specified yield stress of the test piece.
\n2) TS/Y specified ratio refers to ratio of tensile strength to specified yield stress of the test piece.
Additional Note: 1) The steel shall be suitable for welding processes.
Kar [5, 14, 15, 16, 17] has written extensively on PSWC-BAR, and, encouraged by the many benefits, which the use of PSWC-BARs can provide, students at different universities have written a number of theses on the relative performances of concrete elements, reinforced with PSWC-BARs and conventional rebars.
\nBond between rebars and their surrounding concrete is of utmost importance in the context of reinforced concrete.
\nThis bond, when adequately developed, permits composite response of reinforced concrete through effective transfer of forces between concrete and rebar. Any reduction in bond, below a certain level, will lead to a reduction, or in extreme cases, a total loss of load-carrying capacities of the constructed structures, as it happened during the Bhuj earthquake on 26 January 2001 when three buildings, reinforced with epoxy coated bars, collapsed 300 kilometers away in Ahmedabad, India (\nFigure 7\n).
\nIn the case of plain rebars of mild steel or carbon steel, when free from the damaging effects of the ribs as well as the CTD and TMT processes, there will be chemical bond between the mortar in concrete and the hard adherent products of very limited corrosion on the steel material, as in the cases of plain round bars of mild steel or, better still, PSWC-BARs, conforming to plain round rods of Grade A of structural steel in the Indian Standard IS 2062 [8], in which case the rods are given the wave-type configuration (\nFigure 10\n) at the end of the rolling mill process; Kar [14].
\nSimilarly, PSWC-BARs can be made to conform to provisions in existing Standards/Specifications for plain round bars in other countries. Alternatively, Standards may be specifically prepared for PSWC-BARs.
\nThe chemical bond between the mortar in concrete and the hard and adherent products of corrosion on the surface of PSWC-BARs develops shear capacity at the interface of concrete and the rebar for the transfer of forces, through shear, from concrete to rebars.
\nIn the context of reinforced concrete, this is the “bond” engineers have been familiar with.
\nThis should suggest that, technically speaking, there can be no “bond” between concrete and a painted surface, like the surface of an epoxy coated bar (\nFigure 8\n), or similarly between concrete and a stainless steel bar.
\nThe same situation can develop if there will be loose rust on the surface of rebars as in the case of ribbed CTD or TMT bars (\nFigure 6(f)\n), as in IS 1786, which are the most widely used rebars in India.
\n\n\nFigure 6(g)\n shows that the loss of bond rendered the reinforcement, that was provided for load-carrying requirements, insufficient even as minor temperature reinforcements, and thereby led to the development of through-the-thickness shrinkage cracks in the shear walls even though it was a well-engineered project, except that, as per conventional practices in India, ribbed bars, as in IS 1786 [6], are used without the required scrutiny for “bond”, that is set in SubSection 5.6.1 of IS 456 [25].
\nThis is what happened in the case of the ribbed TMT bars in \nFigure 6(f)\n even when the bars were manufactured by a leading manufacturer of rebars and other products of steel in India.
\nThere is more to “bond”.
\nIt is recognized that manufacturers/sellers of epoxy coated and stainless steel bars may not agree to the suggestion that there is no “bond” between epoxy coated or stainless steel bars and the surrounding concrete.
\nIn the absence of any reliable test method to measure “bond” or bond strength in the cases of ribbed bars, engineers too tend to agree with manufacturers and sellers of epoxy coated and stainless steel bars, and they might even suggest that their tests have shown that the bond strength of epoxy coated bars is sixty percent or even eighty percent of that of uncoated bars.
\nThe observations by engineers may be right, but their claims on “bond” are wrong. There are various reasons for it.
\nThere is generally no “bond” between concrete and epoxy coated or stainless steel bars (\nFigures 7\n–\n9\n).
\nAny resistance to pull-out forces in the case of epoxy coated ribbed bars or ribbed stainless steel bars is essentially due to the wedge action of ribs embedded in concrete.
\nIn the present context of bond, the epoxy coating on fusion bonded epoxy coated bars, as in IS 13620 [24], ASTM A775 [21], ASTM A934/A934M [33], ASTM A1055 [23] and similar Standards/Specifications on epoxy coated bars in other countries can be thought of as “coats of paints” as noted in SubSection 5.6.1 of IS 456 [25].
\nRecognizing that coats of paints, like loose rust, oil, etc. could destroy or at least reduce “bond”, IS 456, the basic reinforced concrete code of practice in India, has put words of caution in SubSection 5.6.1 of its Section
In construction with fusion bonded epoxy coated rebars in India or elsewhere, no sand blasting or other treatment is provided so as to meet the requirements set in IS 456 or in any other document, and so as to ensure that there would be competent and adequate bond between such bars and the surrounding concrete.
\nIt is possible that in recognition of this reality, IS 456 in its Section
Though IS 456, the basic Indian Standard for reinforced concrete construction, does not approve of the use of epoxy coated bars as in IS 13620 [24] and stainless steel bars as in IS 16651 [26], such bars, which do not bond with concrete, with attended shortcomings in the performance of concrete constructions, do find use in reinforced concrete constructions in India and elsewhere.
\nIn a series of tests by Varu [32] on thirtythree reinforced concrete columns at Nirma University in Ahmedabad, India, nine columns were reinforced with epoxy coated bars; of which three columns were with epoxy coated plain round bars, three columns were with epoxy-coated ribbed TMT bars of the type in IS 1786 [6], and three columns were with epoxy coated PSWC-BARs.
\nThere is no suggestion that PSWC-BARs and conventional plain round bars may ever be given epoxy coating for protection. But in the test program these bars too were given epoxy coating just to have a more comprehensive understanding of the influence of surface coating (see SubSection 5.6.1 of IS 456 [25]) on load-carrying capacities and “bond” or “engagement”.
\nThe full details will be found in the thesis by Varu [32]. The observations can also be found in a few articles; Kar [2], and Kar, Dave and Varu [30].
\nAmong other observations, it was observed:
unlike in the cases of the twentyfour columns with uncoated rebars of different types, there were clear indications at the failure region of all the nine columns with epoxy coated rebars that there was no bond of concrete/concrete mortar with the epoxy coated bars. A typical case is seen in \nFigure 8\n.
the epoxy coated bars led to failure of the columns at loads which were less than the loads at which the other similarly constructed, but with uncoated bars of same/similar manufacture had failed. It appeared that the coated bars did not participate in sharing loads on the columns; Kar et al. [30].
In the absence of any bond, the use of epoxy coated and stainless steel bars will lead to under-performance of reinforced concrete elements; Kar et al. [30] and Kar [2], and the use of such bars can lead to unacceptable consequences during vibratory loads (\nFigure 10\n), specially during earthquake events (\nFigure 8\n), as it happened when several multi-storey buildings in Ahmedabad collapsed on 26 January 2001 during the earthquake at Bhuj 300 km away.
\nThe failures occurred due to separation between epoxy coated rebars and the surrounding concrete (\nFigure 7\n).
\nThese should be proof enough that any claim of 60–80 percent “bond” between epoxy coated bars and concrete is wrong.
\nThis should suggest that all concrete structures which were constructed with fusion bonded epoxy coated rebars, are suspect. In other words,
the margin of safety in structures with epoxy coated ribbed bars is less than what it may be thought to be as per conventional design; Kar [2] suggested modification to current design practices by considering the “effective bond” or “engagement” instead of assuming that there is competent “bond” between epoxy coated rebars and concrete.
all concrete structures, reinforced with epoxy coated bars, remain specially vulnerable against vibratory loads, including earthquakes, as evidenced in the failure of structures in Ahmedabad during the Bhuj earthquake of 26 January 2001.
In the cases of rebars, with ribs on the surface, where a certain amount of resistance to slippage is available, it is partly due to “bond” and partly due to the interlocking of the ribs with the surrounding concrete. From an engineering point of view, this resistance to slippage may preferably be referred to as “effective bond” or “engagement”, instead of “bond”.
\nThus, though in the context of reinforced concrete, engineers have traditionally used only one term, i.e., “bond”, and though in the context of reinforced concrete, where the rebar is a conventional plain bar of mild steel or carbon steel (\nFigure 6(a)\n), the use of the term “bond” may not create any confusion, the terms “effective bond” and “engagement” may be the more appropriate terms in the case of ribbed bars (\nFigures 2\n and \n6(b)\n and \n(c)\n) and PSWC-BARs (\nFigure 10\n), ribbed stainless steel bars, ribbed epoxy coated bars, polymer coated glass fiber reinforced bars, etc.
\nIn the case of a PSWC-BAR, devoid of ribs or any other surface feature, there will be the “bond” on the entire surface, and in addition, the wave pattern along the length of the bar will provide physical resistance to slippage. The sum total of the “bond” and the “physical resistance” in the case of a PSWC-BAR can be termed as “effective bond” or “engagement”.
\nTests on numerous reinforced concrete beams and columns, with reinforcing bars of different types, at different universities have consistently shown that “the effective bond” or “engagement” is the highest in the case of PSWC-BARs, leading to the highest load-carrying capacities as well as several hundred percent higher ductilities and energy-absorbing capacities compared to the cases of conventional bars without the wave-type configuration; Kar [2].
\nIn the context of reinforced concrete, there should thus be a recognition of “effective bond” or “engagement”, and a clear understanding of “bond”.
\nFor similar reasons, the use of the term “engagement” will hopefully avoid a false belief that there is bond between stainless steel bars and the surrounding concrete, and it will hopefully avoid the type of collapses of reinforced concrete bridges and buildings that Ahmedabad was witness to during the earthquake of 26 January 2001, 300 kilometers away at Bhuj (\nFigure 7\n).
\nThere are instances where chunks of concrete fell down from bridge decks which were constructed with ribbed TMT bars as in IS 1786 [6]. \nFigure 9\n shows one such example.
\nIt should help put a stop to the use of not only the conventional epoxy coated bars, as in IS 13620 [24], but also to bars where the top coat is with epoxy as in ASTM A1055 [23], and also to stainless steel bars as in ASTM A955/A955M [22] and IS 16651 [26], as, unlike in the cases of low carbon steel bars, stainless steel bars will not develop a thin layer of strong adherent rust on their surface for bonding with mortar in concrete.
\nAlso, these bars stand in the way of composite response of concrete and the embedded bars, because of which even the capacity to carry static loads would be less than those which would have been arrived at on the basis of conventional design practices; Kar et al. [30] and Kar [2].
\nIn the context of bond, besides the information provided hereinabove, Kar [14] had suggested that in the case of ribbed bars, coarse aggregates could in places rest on/against neighboring ribs (\nFigure 12\n), thereby blocking mortar from bonding with rebars, and also preventing passivation of rebars at such isolated locations. The void spaces aid the cause of corrosion.
\nBarrier effect of ribs, lugs and protrusions on the surface of ribbed rebars of steel preventing cement mortar from coming in contact with rebar.
In their tests, Mohammed, et al. [34] too observed void spaces beneath ribbed bars, resulting in higher rates of corrosion in ribbed bars than in the case of plain bars.
\nWhether in India or abroad, it has been the practice to assume that the use of ribbed bars provides the required bond between such bars and the surrounding concrete.
\nThough the presence of ribs on the surface of bars decreases the “bond”, when compared to the cases of plain bars, the presence of ribs on the surface of bars may in some cases increase the “engagement”.
\n\n\nFigure 6(g)\n presents a case where the absence of “bond” led to a decrease in the “engagement” between rebar and the surrounding concrete.
\nTo start with, ribs were provided on the surface of rebars of high strength steel with an intent to increase bond between such rebars and concrete. This act boomeranged as it led to an acceleration in the rate of decay in reinforced concrete constructions.
\nThe high strength in steel was/is gained in some cases either through the twisting of the bars beyond yield at a cold state or through quenching. The provision and the presence of the ribs, coupled with the twisting beyond yield or the quenching, lead to corrosion at unacceptably accelerated rates on the surface of the rebars; Alekseev [9, 10], and Kar [1, 5, 11, 12, 13, 14, 15, 16, 17] (\nFigure 6(b)\n and \n(f)\n), resulting in reduction or total destruction of the “bond” (\nFigure 6(g)\n). While the immediate effect of the destruction of “bond” is visible in \nFigure 6(g)\n, the long term effects are visible in \nFigures 3\n–\n6(h)\n and \n(i)\n.
\nBesides questionable “bond”, the ribbed CTD and TMT bars, as in IS 1786 [6], meant for use as rebars in reinforced concrete construction, may not be permitted to be used as rebars, as because, such bars, with high susceptibility to corrosion at accelerated rates, will in many or most cases, fail the qualification test for rebars which have been set in SubSection 5.6.1 for reinforcement in IS 456 [25].
\nAn example will be found in \nFigure 6(g)\n where it is seen that in the construction of six 48–52 storeyed buildings at a site, the shear walls, which in the absence of columns, were reasonably reinforced, developed through-the-thickness shrinkage cracks, about a metre apart as excessive loose rust on ribbed TMT bars (\nFigure 6(f)\n), prevented/destroyed “bond” between concrete and the highly rusted fresh rebars.
\nVisits to construction sites revealed that easily visible through-the-thickness shrinkage cracks in new constructions were very common. This lack of “bond” can lower the load-carrying capacities of such constructions.
\nThe bars, conforming to IS 1786, were thus unfit for construction, at least in the light of the requirements in SubSection 5.6.1 of IS 456.
\nIn the face of all the problems of insufficient “bond” in the case of ribbed rebars of high strength steel, epoxy coated ribbed bars, ribbed bars of stainless steel, and unacceptably high rate of corrosion in rebars, conforming to IS 1786, PSWC-BAR of medium tensile and high tensile steel (\nTable 1\n), conforming to IS 2062 [8], or to any other appropriate Standard/Specification for plain round bars of carbon steel of high strength steel, stands out as the only bar of high strength steel that is free from the varied problems of all other bars of high strength steel.
\nPSWC-BAR, endowed with the property of best “engagement”, i. e., “effective bond” with concrete, also stands out as the only bar, the use of which, besides several-fold enhancement of life span, increases, by several hundred percent ductility and energy absorbing capacity of reinforced concrete construction (\nFigure 11\n) and Kar [2].
\nIt is apparent that there has not been a clear understanding of the phenomenon of “bond” between rebar and concrete, what creates this “bond”, what can affect the development of “bond”, and what are its roles in the performance of reinforced concrete.
\nIt is because of this lack of understanding of “bond” and its significance that made manufacturers and sellers of rebars, designers of reinforced concrete structures, construction engineers, and officials of BIS and such other organizations, who put the stamp of approval on ribbed rebars, overlook all these years the reality, the cautions in text books and Standards which read something like: all reinforcement shall be free from loose mill scales, loose rust and coats of paints, oil, mud or any other substance which may destroy or reduce bond.
\nIt is this total failure to recognize the many significances of “bond” in the realm of reinforced concrete that facilitated the unchecked use of ribbed bars in reinforced concrete construction all these years, and in the process caused very significant losses to property owners, and great harm to the national wealth of countries, as well as to the environment and the global climate.
\nThe facts, that (a) ribbed bars, conforming to IS 1786 and to Standards/Specifications on ribbed bars in other countries, are highly prone to the development of loose rust on the surface of such rebars, (\nFigure 6(f)\n), (b) this rust can “destroy or reduce bond” between concrete and rebars (\nFigure 6(g)\n), (c) without competent bond between rebar and concrete there cannot be reinforced concrete in its true sense, and (d) the loose rust will prevent any possible passivation of rebars by the alkaline pore water in concrete, and thus stand in the way of protection of rebars against corrosion unless concrete constructions will be given surface protection in the nature of waterproofing treatment, have not sunk into the minds of all those who should have known, are obvious from the continued poor performance of the structures in \nFigures 3\n–\n6(h)\n and \n(i)\n, and uncounted other structures which have been and are being constructed with ribbed bars.
\nKar [2] has shown that besides success and failure, and besides the issue of durability, the “effective bond” or “engagement” between rebars and the surrounding concrete may influence the load-carrying capacity, ductility and energy-absorbing capacity of reinforced concrete elements.
\nPercent elongation is an important measure of ductility of rebars, that can influence the performance of the rebar and in turn the performance of concrete elements under load as well as under exposure to the environment; Kar [14]. The percent elongation is of course a very important property that may greatly influence the survivality of reinforced concrete constructions during earthquake events.
\nIn recognition of the fact that the changing material compositions and manufacturing processes, as well as the increasing yield strengths of rebar materials during recent decades, are generally associated with decreasing percent elongation, the Specifications of ASTM International and the Standards of BIS allow/permit the use of rebars with smaller percent elongation properties with increasing yield strength of the rebar material.
\nIt is recognized here that there are certain differences between the gage/gauge lengths in the ASTM and BIS test specimens. However, these differences do not substantially affect the following observations on percent elongation.
\nASTM A615/A615M [18] of 12 Jan, 2016 has set the minimum percent elongation of rebars for Grades 75, 80 and 100, i.e., yield strengths of 520 MPa, 550 MPa and 690 MPa, to 7 percent for rebars having diameters up to 25 mm, and an even lower 6 percent for rebars having diameters greater than 25 mm, whereas for Grade 40 (280 MPa) and Grade 60 (420 MPa) bars, ASTM sets the minimum percent elongation at 12 and 9, respectively.
\nSimilarly, IS 1786 [6], through its Amendment No. 03, dated 19-09-2017, has set the minimum percent elongation at 10.0, 10.0 and 10.0 for rebars of yield strengths 600 MPa, 650 MPa and 700 MPa, whereas it has set allowable percent elongations at 14.5 to 18.0 for different varieties of 415 MPa bars, and 12.0 to 16.0 for different types of 500 MPa bars.
\nSeveral questions arise, viz.,
if once it is recognized that the percent elongation of the steel material for rebars is an important and thus an inviolable property, that is to be set for acceptability of rebars, then why smaller percent elongation properties (as 6 in ASTM A615/A615M [18] and 10 in IS 1786 [6]) be considered permissible for higher yield strength materials, but not for smaller yield strength materials?
or, are the percent elongation properties, set in the Specifications/Standards violable, and the set properties merely represent values which certain manufacturers can achieve in the cases of bars they make?
how is it that when the achievable (with reasonable effort) percent elongation gets smaller and smaller with increasing yield strength, ASTM A615/A615M [18] has set the same elongation at 7 percent or 6 percent for steel having yield strengths of 520 MPa, 550 MPa and 690 MPa?
If 6 percent elongation is considered acceptable for 690 MPa steel, then why should such a low percent elongation be not acceptable in the cases of rebars with steel of lower yield strengths?
how is it that, when the achievable (with reasonable effort) percent elongation gets smaller and smaller with increasing yield strength, IS 1786 [6] has set the same figure of 10 percent for rebars having yield strengths of 600 MPa, 650 MPa and 700 MPa?
how is it that when ASTM A615/A615 M [18] finds it difficult to achieve percent elongation greater than 6 for 600 MPa hot rolled bars, IS 1786 finds a 10 percent elongation achievable for 700 MPa TMT bars, when it is known that, compared to hot rolled processes, as in the USA, the TMT process, as in India, leads to hardening and lowering of ductility and percent elongation properties?
There needs to be a clear understanding of the significance of percent elongation and or ductility of rebars in the context of performance of reinforced concrete elements.
\nIt may be desirable to set, irrespective of the yield strength of steel, a single value, below which the percent elongation or ductility will not be acceptable in the cases of rebars of steel.
\nIn view of the fact that virtually all structures in India and in many other countries are required to be earthquake resistant, a reasonably high value may have to be set for the required percent elongation or ductility of rebars.
\nIn this conflicting scenario, with a view to minimizing the rate of corrosion and also to improve ductility and energy absorbing capacity, PSWC-BAR, conforming to IS 2062, and possessing the property of improving “effective bond” over and above the normally available “bond”, with a minimum percent elongation of 16, is recommended as the rebar of choice. The yield stress will be limited to a maximum of 550 MPa, preferably to 500 MPa; Kar [5].
\nGreater details on the development and mechanical properties of PSWC-BAR, together with design aid, so as to take advantage of the power of PSWC-BAR to enhance load-carrying capacity, as well as ductility and energy-absorbing capacities of reinforced concrete elements, are provided in the article: The Search for an Ideal Rebar for Durable Concrete Construction Leads to PSWC-BAR; Kar [5].
\nA better measure of the mechanical property of a rebar, and that of the performance of a concrete flexural element, reinforced with such a bar, would have been the ductility ratio rather than the arbitrarily selected percent elongation.
\nAssuming that the percent elongation will be at least large enough to ensure that the specified yield strength and the specified ultimate strength of the bar will be achieved, the only other useful information that a percent elongation may provide is a vague understanding that the bar may not break during necessary bending.
\nThat should suggest that vaguely specified percent elongation is an unnecessary specification when separate tests for bending of bars are specified.
\nIn contrast, while tests for yield and ultimate strengths (stresses) will ensure the said strengths (stresses), the information on ductility and the shape of the load-deformation plot of the bar beyond yield will provide important information on an idea about the bendability of a rebar. And in addition, the ductility ratio, coupled with a plot of the load-elongation curve of the bar will provide a great deal of information about the performance of a flexural element beyond the yield stress level of the rebar, provided that the rebar will have the requisite “engagement” with concrete, and it happens best in the case of PSWC-BARs; Kar [2].
\nReinforced concrete is the number one medium of construction. Besides strength, easy formability and availability of the constituent materials, trouble-free long term performance, i.e., durability of concrete structures, constructed with plain round bars of mild steel, having yield stress of around 250 MPa to 280 MPa, had helped reinforced concrete attain this position.
\nIt has been suggested that, in the context of reinforced concrete, besides concrete and rebars, “bond” between such rebars and the surrounding concrete deserves equal consideration.
\nEngineering practice shows that though there is a need for a clear understanding of “bond”, and though the ensurement of adequate “bond” is an essential necessity, these are almost totally neglected.
\nSimilarly, the important property of percent elongation or ductility of the rebar has not been considered with the thoroughness it deserves.
\nWith time, besides significant changes in properties of cement, a constituent component of concrete, the reinforcing bar (rebar) was gradually changed from plain round bars of mild steel to plain round bars of medium tensile steel (yield stress of about 350 MPa) and then on to today’s ribbed rebars of high strength (yield stress 415 MPa to about 700 MPa) steel.
\nThe use of ribbed rebars of high strength steel, susceptible to corrosion at accelerated rates, led to concrete structures reaching states of distress early.
\nIn consideration of durability, ribbed bars, as in IS 1786 in India, and ASTM A615/A615M in the USA and as in such other Standards/Specifications elsewhere, should thus be avoided.
\nThe high susceptibility of ribbed rebars to corrosion may in cases destroy or reduce “bond” between concrete and ribbed rebars of high strength steel.
\nSuch bars may not stand scrutiny for eligibility for use as rebars for reinforced concrete construction. It has been shown that PSWC-BAR, characterized by its plain surface and wave-type configuration, is the most ideal rebar for reinforced concrete construction.
\nWhile the plain surface of PSWC-BARs would ensure that the susceptibility of such bars to corrosion will be several orders of magnitude less than the susceptibility of conventional ribbed bars of high strength steel, the wave-type configuration of PSWC-BARs ensures that the “bond” or “engagement” between such bars and the surrounding concrete is no less than the “bond” between ribbed rebars and concrete.
\nNumerous tests on concrete beams and columns, reinforced with PSWC-BARs, and with ribbed bars, conforming to IS 1786, have consistently revealed that the “effective bond” or “engagement” between PSWC-BARs and the surrounding concrete is greater than the “effective bond” between concrete and ribbed rebars, conforming to IS 1786.
\nIt is this greater “effective bond” that increases the load-carrying capacity, ductility and energy absorbing capacity of concrete elements, reinforced with PSWC-BARs.
\nThe use of PSWC-BAR, characterized by its plain surface and wave-type configuration, at no added effort or cost, can solve the worldwide problem of early distress in reinforced concrete construction.
\nBesides several-fold enhancement of life span, with many added benefits, like greatly reduced life cycle cost, the use of PSWC-BAR increases by several hundred percent the ductility and energy-absorbing capacity of flexural elements of reinforced concrete. It may thus prevent catastrophes during earthquakes.
\nRecommended mechanical properties of PSWC-BARs for durable concrete constructions are provided.
\nIn consideration of requirements for durability and resistance to earthquake forces, the yield stress of steel in PSWC-BAR is recommended to be limited to 550 MPa, and preferably to 500 MPa.
\nThe several-fold enhancement of life span of concrete structures, with the use of PSWC-BARs, instead of conventional ribbed bars, can prevent staggering financial losses to property owners and to national economies of all countries as well as great harm to the environment and to the global climate.
\nAn alternative way to enhance the durability of reinforced concrete construction is to provide, at additional cost, surface protection in the form of waterproofing treatment to concrete structures.
\nChronic myeloproliferative disorders are a group of clonal diseases of the stem cell. It is a group of several diseases with some common features. They derive from a multipotential hematopoietic stem cell. A clone of neoplastic cells in all these neoplams is characterized by a lower proliferative activity than that of acute myeloproliferative diseases. In each of these diseases, leukocytosis, thrombocythemia, and polyglobulia may appear at some stage, depending on the diagnosis [1, 2].
The research on interferon has been going on since the 1950s [3]. Then, the attention was paid to its influence on the immune system. It has been noted that it can exert an antiproliferative effect by stimulating cells of the immune system [4]. In 1987, a publication by Ludwig et al. was published, which reported the effectiveness of interferon alpha in the treatment of chronic myeloproliferative disorders [5].
More and more new studies have been showing the effectiveness of interferon alpha in reducing the number of platelets, reducing the need for phlebotomies in patients with polycythemia vera and also in reducing the number of leukocytes. Moreover, interferon reduced the symptoms of myeloproliferative disorders such as redness and itching of the skin. Additionally, it turned out to be effective in reducing the size of the spleen.
Further studies on the assessment of remission using molecular-level response assessments indicate that the interferon action in chronic myeloproliferation diseases targets cells from the mutant clone with no effect on normal bone marrow cells [6].
Over the years, interferon alpha-2a and interferon alpha-2b have been introduced into the treatment of chronic myeloproliferation, followed by their pegylated forms. The introduction of pegylated forms allowed for a reduction in the number of side effects and less frequent administration of the drug to patients. In recent years, monopegylated interferon alpha-2b has been used to further increase the interval between drug administrations while maintaining its antiproliferative efficacy.
The exact mechanism of action of interferon alpha in the treatment of chronic myeloproliferative disease is still not fully understood, but it has an impact on JAK2 (Janus Kinase) signal transducers and activates the STAT signal pathway (Janus Kinase/SignalTransducer and Activator of Transcription).
Interferon alpha binds to IFNAR1 and IFNAR2c, which are type I interferon receptors. Interferon alpha has an impact on JAK2(Janus Kinase) signal transducers and activates the STAT signal pathway. The disturbances in this signaling pathway are observed in chronic myeloproliferative disorders [7].
Interferon inhibits the JAK-STAT signaling pathway by directly inhibiting the action of thrombopoietin in this pathway [8].
So far, three driver mutations have been described in the course of chronic myeloproliferative diseases that affect the functioning of the JAK-STAT pathway.
JAK2 kinase and JAK1, JAK3, and TYK2 kinases belong to the family of non-receptor tyrosine kinases. They are involved in the intracellular signal transduction of the JAK-STAT pathway. It is a system of intracellular proteins used by growth factors and cytokines to express genes that regulate cell activation, proliferation, and differentiation. The mechanism of JAK activation is based on the autophosphorylation of tyrosine residues that occurs after ligand binds to the receptor. JAK2 kinase transmits signals from the hematopoietic cytokine receptors of the myeloid lineage (erythropoietin, granulocyte-colony stimulating factor thrombopoietin, and lymphoid lineage [9].
A somatic G/T point mutation in exon 14 of the JAK2 kinase gene converts valine to phenylalanine at position 617 (V617F) in the JAK2 pseudokinase domain, which allows constitutive, ligand-independent activation of the receptor to trigger a proliferative signal [10].
Mutation of the MPL gene, which encodes the receptor for thrombopoietin, increases the sensitivity of magekaryocytes to the action of thrombopoietin, which stimulates their proliferation [11].
Malfunction of calreticulin as a result of mutation of the CARL gene leads to the activation of the MPL-JAK/STAT signaling pathway, which is independent of the ligand, as calreticulin is responsible, for the proper formation of the MPL receptor. Consequently, there is a clonal proliferation of hematopoietic stem cells [12].
Below, we provide an overview of some clinical studies on the efficacy of interferon in chronic myeloproliferative disorders.
Polycythemia vera (PV) is characterized by an increase in the number of erythrocytes in the peripheral blood.
Polycythemia vera is caused by a clonal mutation in the multipotential hematopoietic stem cell of the bone marrow. The mutation leads to an uncontrolled proliferation of the mutated cell clone, independent of erythropoietin and other regulatory factors. As the mutation takes place at an early stage of hematopoiesis, an increase of the number of erythrocytes as well as of leukocytes and platelets is observed in the peripheral blood. The cause of proliferation in PV independent from external factors is a mutation in the Janus 2 (JAK2) tyrosine kinase gene. The V617F point mutation in the JAK2 gene is responsible for about 96% mutation, and in the remaining cases the mutation arises in exon 12. Both mutations lead to constitutive activation of the JAK-STAT signaling pathway [13].
As a result of the uncontrolled proliferation, blood viscosity increases, which generates symptoms such as headaches and dizziness, visual disturbances, or erythromelalgia. As the number of all hematopoietic cells, including the granulocytes ones, increases, the difficult to control symptoms of their hyperdegranulation may appear, among which gastric ulcer or skin itching is often observed. During the disease progression, the spleen and liver become enlarged.
The most common complication of the disease is episodes of thrombosis, especially arterial one. During the course of the disease, it can also evolve into myelofibrosis or acute myeloid leukemia.
The treatment of PV is aimed at preventing thromboembolic complications, relieving the general symptoms, the appearance of hepatosplenomegaly as well as preventing its progression.
Each patient should receive an antiplatelet drug chronically, and usually acetylsalicylic acid is the choice. Most often, the treatment is started with phlebotomy in order to rapidly lower the hematocrit level. If cytoreductive therapy is necessary, the drugs of first choice are hydroxycarbamide and interferon [2].
However, the research on the mechanism of the action of interferons is still ongoing. In vitro studies with CD34+ cells from peripheral blood of patients diagnosed with polycythemia vera showed that interferon inhibits clonal changed cells selectively. It was found that interferon alpha-2b and pegylated interferon alpha-2a reduce the percentage of cells with JAK2 V617F mutation by about 40%. Pegylated interferon alpha-2a works by activating mitogen-activated protein kinase P38. It affects CD34+ cells of patients with polycythemia vera by increasing the rate of their apoptosis [6].
A case of a patient with PV with a confirmed chromosomal translocation t(6;8) treated with interferon alpha-2b, which resulted in a reduction of the clone with translocation by 50% from the baseline value, was also described [14].
In 2019, the results of a phase II multicenter study were published, which aimed at assessing the effectiveness of recombinant pegylated interferon alpha-2a in cases of refractory to previously hydroxycarbamide therapy. The study included 65 patients with essential thrombocythemia (ET) and 50 patients with polycythemia vera. All patients had previously been treated with hydroxycarbamide and showed resistance to this drug or its intolerance.
The assessment of the response was performed after 12 months of treatment. Overall response rate to interferon was higher in patients diagnosed with ET than in patients with polycythemia vera. In essential thrombocythemia, the percentage of achieved complete remissions was 43 and 26% of partial remissions. The remission rate in ET patients was higher if calreticulin CALR gene mutation was present. Patients with polycythemia vera achieved complete remission in 22% of cases and partial remission in 38% of cases.
Treatment-related side effects that follow to discontinuation of treatment were reported in almost 14% of patients [15].
The duration of response to treatment with pegylated interferon alpha-2a and the assessment of its safety in long-term use in patients with chronic myeloproliferative disorders was the goal of a phase II of the single-center study. Forty-three adult patients with polycythemia vera and 40 patients with essential thrombocythemia were enrolled in the study. The complete hematological response was defined as a decrease in hemoglobin concentration below 15.0 g/l, without phlebotomies, a resolution of splenomegaly, and no thrombotic episodes in the case of PV, and for essential thrombocythemia—a decrease platelet count below 440,000/μl and two other conditions as above. The assessment of the hematological response was performed every 3–6 months. The median follow-up was 83 months.
The hematological response was obtained in 80% of cases for the entire group. In patients with polycythemia vera, 77% of patients achieved a complete response (CR) while 7% a partial response (PR). The duration of response averaged 65 months for CR and 35 months for PR. In the group of patients diagnosed with essential thrombocythemia, CR was achieved in 73% and PR in 3%. The durance of CR was 58 months and PR was 25 months.
The molecular response for the entire group was achieved in 63% of cases.
The overall analysis showed that the duration of hematological remission and its achievement with pegylated interferon alpha-2a treatment is not affected neither by baseline disease characteristics nor JAK2 allele burden and disease molecular status. There was also no effect on age, sex, or the presence of splenomegaly.
During the course of the study, 22% of patients discontinued the treatment, because of toxicity. Toxicity was the greatest at the beginning of treatment. The starting dose was 450 μg per week and was gradually tapered off.
Thus, on the basis of the above observations, the researchers established that pegylated interferon alpha-2a may give long-term hematological and molecular remissions [16].
The assessment of pegylated interferon alpha-2a in group of patients diagnosed with polycythemia vera only was performed. The evaluation was carried out on a group of 27 patients. Interferon decreased the JAK2 V617F allele burden in 89% of cases. In three patients who were JAK2 homozygous at baseline, after the interferon alpha-2a treatment wild-type of JAK2 reappeared. The reduction of the JAK2 allele burden was estimated from 49% to an average 27%, and additional in one patient the mutant JAK2 allele was not detectable after treatment. It can therefore be postulated that the action of pegylated interferon alpha-2a is directed to cells of the polycythemia vera clone [17].
In 2005, the results of treatment by pegylated interferon alpha-2b of 21 patients diagnosed with polycythemia vera and 21 patients diagnosed with essential thrombocythemia were published. In the case of polycythemia vera in 14 patients, PRV-1 gene mutation was initially detected. In 36% of cases, PRV-1 expression normalized after treatment with pegylated interferon alpha-2b. For the entire group of 42 patients, the remission assessment showed that complete remission was achieved in 69% cases after 6 months of treatment. However, only in 19 patients remission was still maintained 2 years after the start of the study. Pegylated interferon alpha-2b was equally effective in patients with PV and ET. The use and the type of prior therapy did not affect the achievement of remission [18].
Another study with enrolled only PV patients included 136 patients. They were divided into two arms. One group received interferon alpha-2b and the other group received hydroxycarbamide. Interferon dosage was administered in 3 million units three times a week for 2 years and then 5 million units two times a week. Hydroxycarbamide was administered at a dose between 15 and 20 mg/kg/day.
In the group of patients treated with interferon, a significantly lower percentage of patients developed erythromelalgia (9.4%) and distal parasthesia (14%) compared with the group treated with hydroxycarbamide, for whom these percentages were respectively: 29 and 37.5%. Interferon alpha-2b was found to be more effective in inducing a molecular response, which was achieved in 54.7% of cases, in comparison with hydroxycarbamide—19.4% of cases, despite the fact that the percentage of achieved general hematological responses did not differ between the groups and amounted about 70%. The 5-year progression free period in the interferon group was achieved in a higher percentage (66%) than in the hydroxycarbamide group (46.7%) [19].
The most recent form of interferon approved by the
Thanks to these changes to the structure of the molecule, it was possible to achieve a significant increase in its half-life. Ropeginterferon can be administered subcutaneously to patients every 14 days. The clinical trials conducted so far have assessed the ropeginterferon dose from 50 micrograms to a maximum dose of 500 microgams administered as standard every 2 weeks. The possible dose change in case of side effects includes not only the reduction of the drug dose itself, but also the extension of the interval between doses. The extension of the dosing interval up to 4 weeks was assessed.
Ropeginterforn was approved in 2019 by the EMA for the use in patients diagnosed with polycythemia vera without splenomegaly, as monotherapy.
Ropeginterferon, like the previous forms of interferons used in treatment, is contraindicated in patients with severe mental disorders, such as severe depression. It is also a contraindication in patients with noncompensatory standard treatment of disorders of the thyroid gland as well as severe forms of autoimmune diseases. The safety profile of ropeginterferon is similar to that of other forms of alpha interferons. The most common side effects are flu-like symptoms [20].
Ropeginterferon has been shown to exhibit in vitro activity against JAK2-mutant cells. The activity of ropeginterferon against JAK2-positive cells is similar to that of other forms of interferons used actually for standard therapy. Ropeginterferon has an inhibitory effect on erythroid progenitor cells with a mutant JAK2 gene. At the same time, it has almost no effect on progenitor cells without the mutated allele (JAK2-wile-type) and normal CD34+ cells. A gradual decrease of JAK2-positive cells was observed in patients with PV during ropeginterferon treatment. The examination was performed after 6 and 12 months of treatment. In comparison, the reduction in the percentage of JAK2 positive cells in patients treated with hydroxycarbamide was significantly lower.
These results may suggest that ropeginterferon may cause elimination of the mutant clone, but further prospective clinical trials are needed to confirm this theory. The evaluation was performed on a group of patients enrolled in the PROUD-PV study who were treated in France [21].
In 2017, a multicenter study was opened in Italy. The study was of the second phase. In total, 127 patients with polycythemia vera were included in the study. All patients enrolled on the study had low-risk PV. The clinical trial consisted of two arms. Patients received phlebotomies and low-dose aspirin in one arm and ropeginterferon in the other arm. The aim of the study was to achieve a hematocrit of 45% or lower without any evidence of disease progression. Ropeginterferon was administered every 2 weeks at a constant dose of 100 μg.
The response to the treatment was assessed after 12 months. The reduction of hematocrit to the assumed level was achieved in significantly higher percentage of patients in the ropeginterferon group than of patients who received only phlebotomies and aspirin. In addition, none of the patients treated with ropeginterferon experienced disease progression during the course of the study, while among those treated with phlebotomies, 8% of patients progressed.
Grade 4 or 5 adverse events were not observed in patients treated with ropeginterferon, and the incidence of remaining adverse event (AE) was small and comparable in both arms. The most common side effects in the ropeginterferon group were flu-like symptoms and neutropenia; however, the third-grade neutropenia was the most common (8% of cases) [22].
One of the most important clinical studies on the use of ropeginterferon was the PROUD-PV study and its continuation: the CONTINUATION-PV study. These were three-phase, multicenter studies. The aim of the study was to compare the effectiveness of ropeginterferon in relation to hydroxycarbamide. The study included adult patients diagnosed with polycythemia vera treated with hydroxycarbamide for less than 3 years and no cytoreductive treatment at all. In total, 257 patients received this treatment. The patients were divided into two groups: those receiving ropeginterferon or the other being given hydroxycarbamide.
During the PROUD-study, drug doses were increased until the hematocrit was achieved below 45% without the use of phlebotomies, and the normalization of the number of leukocytes and platelets was reached.
The PROUD-PV study lasted 12 months. After this time, the patients continued the treatment under the CONTINUATION-PV study for further 36 months. After the final analysis performed in the 12th month at the end of PROUD study, it was found that the hematological response rates did not differ between the ropeginterferon and hydroxycarbamide treatment groups. These were consecutively 43% in the ropeginterferon arm and 46% in the control arm.
However, after analyzing the CONTINUATION- PV study, it turned out that after 36 months of treatment, the rates of hematological responses begin to prevail in the group of patients receiving ropeginterferon, 53% versus 38% in the control group. Thus, from the above data, it can be seen that the response rate to ropeginterferon increases with the duration of treatment [23].
Another analysis of patients participating in the PROUD and CONTINUATION studies was based on the assessment of treatment results after 24 months, dividing patients into two groups according to age (under and over 60 years).
The initial comparison of both groups of patients showed that older patients had a more aggressive course of the disease. Patients over 60 years of age had a higher percentage of cells with a mutant JAK2 allele. They experienced both general symptoms and some complications, such as thrombosis, more frequently. Both patients under 60 years of age and over 60 years of age in the ropeginterferon arm had a higher rate of molecular response, namely 77.1 and 58.7% compared with the HU remission: 33.3 and 36.1%, respectively. Significantly higher reductions in the JAK2 allele were observed in both groups of patients after ropeginterferon treatment: it was 54.8% for younger patients and 35.1% for elderly patients. For comparison, this difference in the group of patients treated with HU was 4.5 and 18.4%, respectively.
What is more, the age did not affect the frequency of ropeginterferon side effects. In addition, the incidence of adverse ropeginterferon disorders was similar to that observed in the hydroxycarbamide group [24].
Essential thrombocythemia is a clonal growth of multipotential stem cells in the bone marrow. The consequence of this is increased proliferation of megakaryocytes in the bone marrow and an increase in the number of platelets in the peripheral blood. The level of platelets above 450,000/μl is considered a diagnostic criterion.
Essential thrombocythemia may progress over time to a more aggressive form of myeloproliferation, i.e., myelofibrosis. The disease can also evolve into acute myeloid leukemia or myelodysplastic syndrome, both with very poor prognosis. Thromboembolic complications are serious, and they concern over 20% of patients. Thrombosis occurs in the artery and venous area. Moreover, in patients with a very high platelet count, above 1,000,000/μl, bleeding may occur as a result of secondary von Willebrand syndrome [1, 2].
The treatment of ET is primarily aimed to prevent thrombotic complications.
In low-risk patients, only acetylsalicylic acid is used. In cases of high-risk patients, hydroxycarbamide is the first-line drug for most patients. Anagrelide and interferon are commonly used as second-line drugs.
Due to the possible effects of hydroxycarbamide of cytogenetic changes in the bone marrow cells after long-lasting usage, some experts recommend the use of interferon in younger patients in the first line. Interferon is also used as the drug of choice in patients planning a pregnancy [25].
The efficacy of pegylated interferon alpha-2a was assessed on the basis of the group of 39 patients with essential thrombocythemia and 40 patients with polycythemia vera.
Of the overall group, 81% of patients were previously treated prior to the study entry. The patients received pegylated interferon alpha-2a in a dose of 90 μg once a week. The dose of 450 μg was associated with a high percentage of intolerance.
In patients with essential thrombocythemia, the complete remission was achieved in 76%, while the overall hematological response rate brought 81%. Moreover, the molecular remission was achieved in 38%, in 14% of cases, JAK2 transcript became not detectable.
Patients diagnosed with polycythemia vera achieved 70% complete hematological remission and 80% general hematological response to treatment. JAK2 transcript was undetectable in 6% of patients. Molecular remission was achieved in 54% of cases.
Pegylated interferon alpha-2a at the dose of 90 μg per week was very well tolerated. In total, 20% of patients experienced a grade of 3 or 4 of adverse reaction, which was neutropenia. In addition, an increase in liver function tests was observed. Grade 4 of AE was not observed among patients who started the treatment with 90 μg/week while grade 3 neutropenia was an adverse event in only 7% of cases [26].
The effect of interferon alpha-2b treatment in patients with ET and PV was investigated. The study was prospective. Some of the results concerning the group of patients with polycythemia vera are presented in the subsection on polycythemia vera. In total, 123 patients with diagnosed essential thrombocythemia participated in the study. All of them received interferon alpha-2b. The patients were divided into two groups depending on the presence of the JAK2 V617F mutation. The enrolled patients were between 18 and 65 years of age. The treatment they received was, sequentially, interferon alpha-2b in the dose of 3 million units three times a week for the first 2 years, after which time the dose was changed into a maintenance dose, which amounted to 5 million units two times a week.
The analysis showed that the patients with the JAK2 V617F mutation present in a higher percentage achieved an overall hematological response as well as a complete hematological response. The overall hematological response was achieved in 83% of patients with JAK2 mutation, and the complete hematological remission was achieved in 23 cases. In the group of ET patients without the JAK2 V617F mutation, overall hematological response was achieved in 61.4%, while the complete hematological remission was achieved in 12 patients. The 5-year progression-free survival was obtained in 75.9% in the JAKV617F group and only in 47.6% without the mutation.
A significant proportion of patients experienced mild side effects. Grade 3 and 4 of adverse events were severe, most of them being a fever. The isolated cases of elevated liver tests and nausea have also been reported [19].
Pegylated interferon alpha-2b in patients with essential thrombocythemia who were previously treated with hydroxycarbamide, anagrelide, and other forms of interferon alpha, however, due to the lack of efficacy or toxicity, the patients required a change of treatment, was assessed. Pegylated interferon alpha-2b turned out to be effective in these cases. It led to the complete hematological remission in 91% of patients after 2 months of therapy, and in 100% of patients after 4 months. However, merely 11 patients participated in the study. Also only two patients required treatment discontinuation due to the side effects such as depression and general fatigue grade 3 [27].
In case of pregnant patients, interferon is currently considered the only safe cytoreductive drug. Over the years, several analyses of the results of interferon treatment during pregnancy have been carried out.
The assessment of 34 pregnancies in 23 women diagnosed with ET was performed retrospectively. All the pregnancies included in the analysis were of high risk. This high risk was associated with a high platelet count above 1,500,000/μl, a history of thrombotic episode, severe microcirculation disorders, or a history of major hemorrhage.
It turned out that the use of interferon allowed the birth of an alive child in 73.5% of cases. There was no difference in efficacy between the basic and pegylated forms of interferon alpha. In pregnancies without interferon treatment, the percentage of live births was only 60%. Moreover, it was not found if the presence of the JAK2 V617F mutation had any influence on the course of pregnancy [28].
An analysis of the course of pregnancy in patients with ET was assessed in Italy. Data from 17 centers were taken into account. Data from 122 pregnancies were collected from 92 women. In patients diagnosed with essential thrombocythemia, the risk of the spontaneous loss of pregnancy is about 2.5 times higher than among the general population. In the contrary to the study quoted above, it was found that the presence of the JAK2 mutation increases the risk of pregnancy loss. The proportion of live births in patients exposed to interferon during pregnancy was 95%, compared with 71.6% in the group of patients not treated with interferon.
The multivariate analysis also showed that the use of acetylsalicylic acid during pregnancy had no effect on the live birth rate of patients with ET [29].
Whatever its form, interferon is the drug of first choice in pregnancy. Hydroxycarbamide and anagrelide should be withdrawn for about 6 months, and at least for 3 months, before the planned conception. Experts recommend the use of interferon in high-risk pregnancies [30]. A Japanese analysis of 10 consecutive pregnancies in ET patients showed 100% live births in patients who received interferon [31].
In myelofibrosis (MF), monoclonal megakaryocytes produce cytokines that stimulate the proliferation of normal, non-neoplastic fibroblasts and stimulate angiogenesis. The consequence of this is the gradual fibrosis of the bone marrow, impaired hematopoiesis in the bone marrow, and the formation of extramedullary location mainly in the sites of fetal hematopoiesis, i.e., in the spleen and the liver.
The production of various cytokines by neoplastic megakaryocytes leads to the proliferation of normal, noncancerous fibroblasts as well as to increased angiogenesis.
Progressive bone marrow fibrosis leads to worsening anemia and thrombocytopenia. On the other hand, the production of proinflammatory cytokines by megakaryoblasts leads to the general symptoms such as weight loss, fever, joint pain, night sweats, and consequently, progressive worsening of general condition.
The prognosis for myelofibrosis is poor. In about 20% of patients, myelofibrosis evolves into acute myeloid leukemia with poor prognosis.
Currently, the only effective method of treatment that gives a chance to prolong the life is allogeneic bone marrow transplantation. However, this method is only available to younger patients.
The goal of treatment of patients who have not been qualified for allotranspalntation is to reduce the symptoms and to improve the patient’s quality of life. In case of leukocytosis cytoreducing drugs, such as hydroxycarbamide, melphalan, or cladribine can be used. They cause a reduction in the number of leukocytes and may, to some extent, inhibit splenomegaly. Interferon alpha has been used successfully for the treatment of myelofibrosis for many years. The results of its effectiveness will be presented below [2].
Currently, the JAK2 inhibitor ruxolitinib is approved for the treatment of myelofibrosis with enlarged spleen in intermediate and high-risk patients. Ruxolitinib reduces the size of the spleen, reduces general symptoms, and improves the quality of life; however, it does not prolong the overall survival of patients [32].
In 2015, the results of a retrospective study were published to compare the histological parameters of the bone marrow before and after interferon treatment. Twelve patients diagnosed with primary myelofibrosis as well as post-PV MF and post-ET MF were enrolled in the study. Patients were treated with pegylated recombinant interferon alpha-2a or recombinant interferon alpha-2b in standard doses. The time of treatment was from 1 to 10 years. Some patients had previously been treated with hydroxycarbamide or anagrelide. In all cases, karyotype was normal. The prognostic factor of Dynamic International Prognostic Scoring System (DIPSS) was assessed at the beginning as well as during the treatment.
Bone marrow cellularity decreased in cases with increased bone marrow cellularity before the treatment. After the interferon treatment, a reduction in the degree of bone marrow fibrosis was found. The parameters, such as the density of naked nuclei and the density of megakaryocytes in the bone marrow, also improved.
It proves that if the JAK2 V617F mutation had been present, DIPSS was decreased after interferon treatment. This relationship was not observed in patients without the JAK2 V617F mutation. The improvement in peripheral blood morphological parameters and the overall clinical improvement correlated with the improvement in the assessed histological parameters of the bone marrow.
Before the initiation of interferon, seven patients had splenomegaly. During the treatment with interferon, the complete resolution of splenomegaly was achieved in 17% of patients (two cases), and its size decreased in 25% (three cases). A good clinical response was achieved in 83% during interferon therapy. There was no significant difference in response between the two types of interferon used [33].
A prospective study was also conducted in patients with low and intermediate-1 risk group myelofibrosis. Seventeen patients were enrolled. Patients received interferon alpha-2b (0.5–3 milion units/three times a week) or pegylated interferon alpha-2a (45–90 μg/week). The duration of therapy was on average 3.3 years.
Most of the patients responded to the treatment. Partial remission was found in seven patients and complete remission in two patients. Moreover, in four cases, the disease was stabilized and in one case the clinical improvement was achieved. Three patients did not respond to treatment at all and progressed to myelofibrosis. Additionally, the assessment in reducing spleen size was performed. At baseline, 15 patients have splenomegaly, nine of them achieved the compete regression of spleen size [34].
However, the efficacy of interferon in the treatment of myelofibrosis appears to be limited only to a less advanced form, when the bone marrow still has an adequate percentage of normal hemopoiesis and the marrow stroma is not significantly fibrotic. In more advanced stages, interferon was not shown to have any significant effect on the regression of the fibrosis process [35].
In 2020, the results of the COMBI study were published. That was a two-phase, multicenter, single-arm study that investigated the efficacy and safety of the combination of ruxolitinib and pegylated interferon alpha. Thirty-two patients with PV and 18 patients with primary and secondary myelofibrosis participated in the study. The patients were at age 18 and older. Remission was achieved in 44% of myelofibrosis cases, including 28% (5 patients) of complete remission. In patients with PV, the results were slightly worse: 31% of remissions, including 9% of complete remissions. Patients received pegylated interferon alpha-2a (45 μg/week) or pegylated interferon alpha-2b (35 μg/week) in low doses and ruxolitinib in doses of 5–20 mg twice a day.
For the entire group of patients (with PV and MF), the initial JAK2 allele burden was 47% at baseline, and after 2 years of treatment with interferon and ruxolitinib, it decreased to 12%.
The treatment toxicity was low. The highest incidence of side effects occurred at initiation of therapy. It was mostly anemia and thrombocytopenia.
The observations from the COMBI study show that, for the combination of interferon in lower doses with ruxolitinib, it may be effective and well tolerated even in the group of patients who had intolerance to interferon used as the only drug in higher doses. The combined treatment improved the bone marrow in terms of fibrosis and its cellularity. It also allowed to improve the value of peripheral blood counts [36].
It is currently known that some of the additional mutations are associated with a worse prognosis in patients with myelorpoliferation, including patients with myelofibrosis. Some of these mutations have been identified as high-risk molecular mutations. These are ASXL1, EZH2, IDH1/2, or SRSF2. Earlier studies have shown their association with a more aggressive course of the disease, worse prognosis, and shorter survival of patients, as well as a poorer response to treatment. Due to their importance, they have been included in the diagnostic criteria of myelofibrosis [37].
It is also known that the presence of driver mutations, i.e., JAK2, CALR, and MPL or triple negativity, may affect the course of myeloproliferation, including the incidence of thromboembolic complications.
The assessment of the influence of driver mutations and a panel of selected additional mutations on the effectiveness of interferon treatment in patients with myelofibrosis was performed on a group of 30 patients. Only the patients with low- and intermediate-1-risk were enrolled in the study. The treatment with pegylated interferon alpha-2a or interferon alpha-2b resulted in a complete remission in two patients and partial remission in nine patients. The disease progressed in three cases. One patient relapsed and four died. The remaining patients achieved a clinical improvement or disease stabilization. In the studied group, it was not found if the effectiveness of interferon treatment was influenced by the lack of driver mutations. Among the group of four patients with additional mutations, two died and one had disease progression. It was a mutation of ASXL1 and SRSF2. The treatment with interferon in patients without additional molecular mutations in the early stages of the disease may prevent further progression of the disease [38].
The side effects of interferon in the group of patients with myelofibrosis are similar to those occurring after the treatment of other chronic myeloproliferative diseases. The most frequently described are hematological toxicity- anemia and thrombocytopenia, less often is the appearance of leukopenia. Hematological toxicity usually resolves with dose reduction or extension of the dose interval. The most frequently nonhematological toxicity was fatigue, muscle pain, weakness, and depression symptoms. All symptoms are usually mild and do not exceed grade 2 [38].
However, the use of interferon in the treatment of myelofibrosis has not been recommended as a standard therapy. Interferon is still being evaluated in clinical trials, or it is used in selected patients as a nonstandard therapy in this diagnosis.
Mastocytosis is characterized by an excessive proliferation of abnormal mast cells and their accumulation in various organs.
The basis for the development of mastocytosis is ligand-independent activation of the KIT receptor, resulting from mutations in the KIT proto-oncogene. The KIT receptor is a trans membrane receptor with tyrosine kinase’s activity. Its activation stimulates the proliferation of mast cells. That excessive numbers of mast cells infiltrate tissues and organs and release mediators such as histamine, interleukine-6, tryptase, heparin, and others, which are responsible for the appearance of symptoms typical of mastocytosis. In addition, the infiltration of tissues for mast cells itself causes damage to the affected organs.
The prognosis of mastocytosis depends on the type of the disease. In the case of cutaneous mastocytosis (CM), in the majority of cases prognosis is good and the disease does not shorten the patient’s life, but in aggressive systemic mastocytosis (ASM), the average follow-up is about 40 months. Mast cell leukemia has a poor prognosis with a median follow-up of approximately 1 year.
Systemic mastocytosis usually requires the implementation of cytoreductive therapy. The first line of therapy is interferon alone or its combination with corticosteroids. In aggressive systemic mastocytosis, the first line in addition to interferon 2-CdA can be used. An effective drug turned out to be midostaurin in the case of the present KIT mutation. In patients without the KIT D816V mutation, treatment with imatinib may be effective. In the case of mast cell leukemia, multidrug chemotherapy is most often required, as in acute leukemias, followed by bone marrow transplantation [39].
Systemic mastocytosis requiring treatment is a rare disease, this is why the studies available in the literature evaluating various therapies concern mostly small groups of patients.
In 2002, the French authors presented their experiences on the use of interferon in patients with systemic mastocytosis. They included 20 patients. The patients received interferon alpha-2b in gradually increased doses.
The patients were assessed after 6 months. In cases in which bone marrow was infiltrated for mast cells at baseline, it still remained infiltrated after 6 months of treatment.
However, the responses were obtained in terms of symptoms related to mast cell degranulation. Partial remission was achieved in 35% of patients and minor remission in 30%. It concerns mainly skin lesions and vascular congestion. Moreover, the assessment of the histamine level in the plasma revealed a decrease of it in patients who previously presented symptoms related to the degranulation of mast cells, such as gastrointestinal disorders and flushing.
A high percentage of side effects were found during treatment. They concerned 35% of patients. Depression and cytopenia were most frequent ones [40].
Another analysis was a report of five patients with systemic mastocytosis treated with interferon and prednisolone. All patients received interferon alpha-2b in a dose of 3 million units three times a week and four patients additionally received prednisolone. Four patients responded to interferon treatment at varying degrees. One patient, who at baseline had bone marrow involvement by mast cells in above 10%, progressed to mast cell leukemia. In two patients, the symptoms C resolved completely and in one of them they partially disappeared. In one case, stabilizing disease was achieved [41].
In 2009, a retrospective analysis of patients treated with cytoreductive therapy due to mastocytosis was published. The authors collected data from 108 patients treated at the Mayo Clinic. This analysis allowed for the comparison of the efficacy of four drugs used in systemic mastocytosis. There were interferon alpha alone or in the combination with prednisone—among 40 patients, hydroxycarbamide—among 26 ones, imatinib—among 22 persons, and 2-chlorodeoxyadenosine (2-CdA)—among 22 patients.
After dividing the patients into three additional groups on the basis of the type of mastocytosis—indolent systemic mastocytosis, aggressive systemic mastocytosis, and systemic mastocytosis associated with another clonal hematological nonmast cell lineage disease (SM-AHNMD)—the effectiveness of each of type of therapy was assessed.
The highest response rates in indolent and aggressive mastocytosis were achieved with interferon treatment. They were 60% of the responses in both groups, and in the SM-AHNMD group of patients, the percentage was also one of the highest and amounted to 45%. The second most effective drug was 2-CdA. The response rates were 56% for indolent MS, 50% for aggressive MS, and 55% for SM-AHNMD. The patients treated with imatinib achieved response in 14, 50, and 9% by following groups, respectively. In contrast, patients with indolent and aggressive systemic mastocytosis did not respond to hydroxycarbamide treatment at all. The response rate in both groups was 0%. However, patients with MS associated with another clonal hematological nonmast cell lineage disease achieved 21% response to hydroxycarbamide. Additionally, it was found that only interferon relieved symptoms caused by the release of inflammatory mediators by mast cells.
The additional analysis showed no influence of the TET 2 mutation on the response to treatment [42].
In the literature, there are also single cases of mastocytosis presenting trials of nonstandard treatment. That is description of a patient with systemic mastocytosis with mast cell bone marrow involvement. Mutation of c-kit Asp816Val was present. Patient progressed despite treatment with dasatinib and 2-chlorodeoxyadenosine. The patient developed symptoms related to the degranulation of mast cells and increased ascites.
The patient was treated with pranlukast, which is an anti-leukotriene receptor antagonist due to an asthma episode. The rate of ascites growth decreased significantly after one administration. The patient required paracentesis every 10 days and not every 3 days, as before starting to take the drug. After 15 days of treatment with pranlukast, the patient received interferon alpha, which resulted in complete regression of ascites, resolution of pancytopenia, and complete disappearance of the c-kit mutation clone. The infiltration of mast cells in the bone marrow significantly decreased [43].
Interferon alpha was also effective in a patient with systemic mastocytosis associated with myelodysplastic syndrome with the c-kit D816V mutation, which was refractory to imatinib treatment [44].
Interferon alpha also proved to be effective in the treatment of osteoporotic lesions appearing in the course of mastocytosis.
The series of 10 cases with resolved mastocytosis and osteoporosis-related fractures was presented in 2011. The patients received interferon alpha in a dose of 1.5 million units three times a week as well as pamindronic acid. The patients were treated for an average of 60 months. For the first 2 years, pamindronate was given at a dose of 1 mg/kg every month, and then every 3 months.
During the course of the study, no patient had a new-bone fracture. The level of alkaline phosphatase decreased by 25% in relation to the value before treatment and tryptase by 34%. Bone density increased during treated with interferon and pamindronate. The increase was on average 12% in the spine bones and 1.9% in the hip bones. At the same time, there was no increase in the density of the hip bone and a minimal increase in the density of the spine in patients treated with pamindronate alone.
The results of this observation suggest that it is beneficial to add low doses of interferon alpha to pamindronate treatment in terms of bone density increase [45].
That experiences show that interferon used in systemic mastocytosis significantly improves the quality of life of patients by inhibiting the symptoms caused by degranulation of mast cells. They prevent bone fractures and, in some patients, they cause remission of bone marrow infiltration by mast cells.
Chronic neutrophilic leukemia (CNL) is a very rare disease. It is characterized by the clonal proliferation of mature neutrophils.
The diagnostic criteria proposed by the World Health Organization (WHO) comprise leukocyte counts above 25,000/μl (including more than 80% of rod and segmented
Physical examination often shows enlargement of the liver and spleen, moreover, patients complain on weight loss and weakness [1].
The prognosis varies. The average survival time for patients with CNL is less than 2 years.
Only few descriptions of chronic neutrophilic leukemia are available in the literature, and these are mostly single case reports.
Because it is an extremely rare disease, there are no established and generally accepted treatment standards. In most cases, patients are given hydroxycarbamide or interferon. Patients who are eligible for a bone marrow transplant may benefit from this treatment. Bone marrow allotransplantation remains the only method that gives a chance for a significant extension of life.
The German authors presented a series of 14 cases of chronic neutrophilic leukemia. The group of patients consisted of eight women and six men. The average age was 64.7 years. From the entire group of patients, longer survival was achieved only in three cases. One of these patients was treated with interferon alpha and achieved hematological remission, the other underwent bone marrow allotransplantation from a family donor, and the third one was treated with hydroxycarbamide and transfusions as needed. The follow-up period of the patient after allogeneic matched related donor transplantation (allo-MRD) was 73 months, and for the patient after interferon treatment it was 41 months.
The remaining patients died within 2 years of diagnosis. Six patients, the largest group, died due to intracranial bleeding, three patients died because of leukemia cell tissue infiltration, one patient because of the disease transformation into leukemia, and one patient because of pneumonia [46].
It can be seen from these experiences that treatment with interferon alpha can significantly extend the survival time of patients.
The case of a 40-year-old woman diagnosed with chronic neutrophilic leukemia is presented by Yassin and coauthors. Initially, the patient had almost 41,000 leukocytes in the peripheral blood. In a physical examination, splenomegaly and hepatomegaly were not present. Patient received pegylated interferon alpha-2a. The initially dose was 50 μg once a week for the first 2 weeks, then the dose was increased to 135 μg weekly for 6 weeks, and then the dose interval was extended to another 2 weeks. As a result of the treatment, the general condition of the patient improved and the parameters of peripheral blood counts were normalized [47].
Another case report presented in the literature describes a 41-year-old woman diagnosed with CNL accompanied by focal segmental glomerulosclerosis (FSGS). The patient had increasing leukocytosis for several months. On the admission to the hospital, leukocytosis was 94,000/μl. Moreover, the number of platelets in the morphology exceeded 1,000,000/μl. More than a year earlier, the patient had splenectomy due to splenomegaly and spleen infraction.
Additionally, JAK2 V617F mutation was found. Some authors suggest that the presence of JAK2 mutation may be associated with longer survival in CNL.
The patient received hydroxycarbamide for 3 months and reduction in the number of leukocytes was achieved. After this time, interferon alpha-2b was added to hydroxycarbamide. As a result, focal segmental glomerulosclerosis disappeared and the renal tests improved [48].
Another case of chronic neutrophilic leukemia with a JAK2 gene mutation concerns a 53-year-old man. The patient’s baseline leukocytosis was 33,500/μl, including the neutrophil count of 29,700/μl. The patient also had splenomegaly.
The treatment with interferon alpha-2b at a dose of 3 million units every other day was started. After a month of treatment, the number of leukocytes was reduced to less than 10,000/μl. Then the patient was treated chronically with interferon alpha-2b in doses of 3 million units every 2 weeks. As a result of the therapy, the number of leukocytes remains between 8 and 10,000/μl. The patient remains in general good condition [49].
A series of two CNL cases are also shown. The first patient was a 70-year-old woman with stable leukocytosis of about 35,000/μl and the remaining morphology parameters in normal range. The patient was only observed for 5 years until hepasplenomegaly progressed rapidly. Then, interferon alpha-2b was included. Due to the treatment, the rapid regression of hepatosplenomegaly was achieved.
The second case is a 68-year-old woman with baseline leukocytosis of almost 14,000/μl. In this case, the treatment with hydroxycarbamide was started immediately. However, no improvement was achieved. After 6 weeks of HU treatment, interferon alpha-2b 3 million units 3 times a week was implemented and leukocytosis decreased. Due to the interferon treatment, the disease stabilized for a long time. Because the patient experienced an adverse reaction, a severe flu-like syndrome, interferon was discontinued. After interferon withdrawal, the disease progressed gradually and the treatment attempts by busulfan and 6-mercaptopurine were unsuccessful. Therefore, interferon was readministered and the disease went into remission. Interferon treatment was continued at a reduced dose. The disease regression was achieved again.
Additionally, the patient showed an improvement in the function of granulocytes in terms of phagocytosis and an improvement in neutral killer (NK) cell function after treatment with interferon [50].
The above examples show that interferon alpha is effective in the treatment of chronic neutrophilic leukemia. The side effects are rare and can be managed with dose reductions. Moreover, in these cases, interferon is also effective in a reduced dose. Disease remission or regression can be achieved without typical of CNL complications, such as intracranial bleeding.
Interferon has been used in the past to treat chronic myeloid leukemia. The treatment with tyrosine kinase inhibitors is now a standard practice. However, in a small number of patients, they are ineffective or exhibit unmanageable toxicity. Therefore, the attempts are underway to use interferon in combination with TKI in lower doses, which is to ensure the enhancement of the antiproliferative effect while reducing the toxicity.
There are ongoing attempts to use ropeginterferon in patients diagnosed with chronic myeloid leukemia, in whom treatment with imatinib alone has not led to deep molecular response (DMR). The first phase study was conducted in a small group of patients with chronic myeloid leukemia. The patients in first chronic phase treated with imatinib who did not achieve DMR, but in complete hematologic remission and complete cytogenetic remission, were included in the study. Patients have been treated with imatinib for at least 18 months. Twelve patients were enrolled in the study, and they completed the study according to the protocol. These patients received additional ropeginterferon to imatinib and four achieved DMR. Low toxicity was observed during the treatment. Among the hematological toxicities, neutropenia was the most common. There was no nonhematological toxicity with a degree higher than 1/2 during the treatment. Moreover, it has been found that better effects and fewer side effects are obtained when ropeginterferon is administered for a longer time, but in lower doses. The comparison of the effectiveness of interferon in chronic myeloproliferative disorders based on selected articles is presented in Table 1 [51].
Source | Type of trial | Interferon | Diagnosis | No. | Prior treatment status | Response rate |
---|---|---|---|---|---|---|
Yacoubet al. [15] | Phase II, multicenter | Pegylated IFN alfa-2a | PV | 50 | Resistance to HU or HU intolerance | CR:22% PR:38% |
ET | 65 | CR:43% PR:26% | ||||
Masarova et al. [16] | Phase II, single-center | Pegylated IFN alfa-2a | PV | 43 | Untreated or previously treated with cytoreductive therapy | CR:77% PR:7% |
ET | 40 | CR:73% PR:3% | ||||
Samuelsson et al. [18] | Phase II | Pegylated IFN alfa-2b | PV | 21 | Untreated or previously treated with cytoreductive therapy | CR: 69% for the entire group |
ET | 21 | |||||
Huang BT et al. [19] | Open label, multicenter | IFN alfa-2b | PV | 136 | Untreated or previously treated with cytoreductive therapy | OHR:70% Molecular response:54.7% |
ET | 123 | OHR (JAK2+ patients):83% CHR:23 cases OHR (JAK2-patients): 61.4% CHR:12 cases | ||||
Gisslinger et al. [23] | phase III, multicenter | Ropeginterferon | PV | 257 | Previously treated | OHR:53% |
Quintás-Cardama et al. [26] | phase II | Pegylated IFN alfa-2a | PV | 40 | Untreated or previously treated with cytoreductive therapy | OHR:80% CR:70% Molecular remission:54% |
ET | 39 | OHR:81% CR:76% Molecular remission:38% | ||||
Sørensen et al. [36] | Phase III, multicenter, COMBI | Pegylated IFN alfa-2a with ruxolitinib or Pegylated IFN alfa-2b with ruxolitinib | PV | 32 | Untreated or previously treated with cytoreductive therapy | OHR:44% CR:28% |
MF | 18 | OHR:31% CR:9% | ||||
Casassus et al. [40] | Open label, multicenter | IFN alpha-2b | Mastocytosis | 20 | Untreated and previously treated | PR:35% Minor remission: 30% |
Comparison of the effectiveness of interferon in chronic myeloproliferative disorders.
PV: polycythemia vera; ET: essential thrombocythemia; MF: myelofibrosis; HU: hydroxycarbamide/hydroxyurea; CR: complete remission; PR: partial remission; and OHR: overall hematological response.
Interferon alpha appears to be an effective and safe drug in the most type of chronic myeloproliferative disorders. Nowadays, all forms of its using have similar effectiveness. Interferon alpha can be effective even in cases of resistance for first-line treatment. Trial research is currently underway to combine it with some new drugs, such as ruxolitinib, and to add it to the already well-established therapy, it is a promising option for patients with refractory disease.
From time to time, new forms of interferon, such as ropeginterferon, are introduced, which gives hope for better effectiveness, better safety profile, and greater comfort in its use for patients who have to be treated for many years. In the case of the use of interferons alpha in the treatment of chronic myeloproliferative diseases, there are still opportunities to extend its use and to study its combination with newly introduced drugs.
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Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:42,paginationItems:[{id:"82914",title:"Glance on the Critical Role of IL-23 Receptor Gene Variations in Inflammation-Induced Carcinogenesis",doi:"10.5772/intechopen.105049",signatures:"Mohammed El-Gedamy",slug:"glance-on-the-critical-role-of-il-23-receptor-gene-variations-in-inflammation-induced-carcinogenesis",totalDownloads:15,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Chemokines Updates",coverURL:"https://cdn.intechopen.com/books/images_new/11672.jpg",subseries:{id:"18",title:"Proteomics"}}},{id:"82875",title:"Lipidomics as a Tool in the Diagnosis and Clinical Therapy",doi:"10.5772/intechopen.105857",signatures:"María Elizbeth Alvarez Sánchez, Erick Nolasco Ontiveros, Rodrigo Arreola, Adriana Montserrat Espinosa González, Ana María García Bores, Roberto Eduardo López Urrutia, Ignacio Peñalosa Castro, María del Socorro Sánchez Correa and Edgar Antonio Estrella Parra",slug:"lipidomics-as-a-tool-in-the-diagnosis-and-clinical-therapy",totalDownloads:9,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Fatty Acids - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11669.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82440",title:"Lipid Metabolism and Associated Molecular Signaling Events in Autoimmune Disease",doi:"10.5772/intechopen.105746",signatures:"Mohan Vanditha, Sonu Das and Mathew John",slug:"lipid-metabolism-and-associated-molecular-signaling-events-in-autoimmune-disease",totalDownloads:17,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Fatty Acids - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11669.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82483",title:"Oxidative Stress in Cardiovascular Diseases",doi:"10.5772/intechopen.105891",signatures:"Laura Mourino-Alvarez, Tamara Sastre-Oliva, Nerea Corbacho-Alonso and Maria G. 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She is also the Global Harmonization Initiative (GHI)",institutionString:"Australian College of Business & Technology",institution:{name:"Kobe College",institutionURL:null,country:{name:"Japan"}}}]},{type:"book",id:"6820",title:"Keratin",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6820.jpg",slug:"keratin",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Miroslav Blumenberg",hash:"6def75cd4b6b5324a02b6dc0359896d0",volumeInSeries:2,fullTitle:"Keratin",editors:[{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}}]},{type:"book",id:"7978",title:"Vitamin A",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7978.jpg",slug:"vitamin-a",publishedDate:"May 15th 2019",editedByType:"Edited by",bookSignature:"Leila Queiroz Zepka, Veridiana Vera de Rosso and Eduardo Jacob-Lopes",hash:"dad04a658ab9e3d851d23705980a688b",volumeInSeries:3,fullTitle:"Vitamin A",editors:[{id:"261969",title:"Dr.",name:"Leila",middleName:null,surname:"Queiroz Zepka",slug:"leila-queiroz-zepka",fullName:"Leila Queiroz Zepka",profilePictureURL:"https://mts.intechopen.com/storage/users/261969/images/system/261969.png",biography:"Prof. Dr. Leila Queiroz Zepka is currently an associate professor in the Department of Food Technology and Science, Federal University of Santa Maria, Brazil. She has more than fifteen years of teaching and research experience. She has published more than 550 scientific publications/communications, including 15 books, 50 book chapters, 100 original research papers, 380 research communications in national and international conferences, and 12 patents. She is a member of the editorial board of five journals and acts as a reviewer for several national and international journals. Her research interests include microalgal biotechnology with an emphasis on microalgae-based products.",institutionString:"Universidade Federal de Santa Maria",institution:{name:"Universidade Federal de Santa Maria",institutionURL:null,country:{name:"Brazil"}}}]},{type:"book",id:"7953",title:"Bioluminescence",subtitle:"Analytical Applications and Basic Biology",coverURL:"https://cdn.intechopen.com/books/images_new/7953.jpg",slug:"bioluminescence-analytical-applications-and-basic-biology",publishedDate:"September 25th 2019",editedByType:"Edited by",bookSignature:"Hirobumi Suzuki",hash:"3a8efa00b71abea11bf01973dc589979",volumeInSeries:4,fullTitle:"Bioluminescence - Analytical Applications and Basic Biology",editors:[{id:"185746",title:"Dr.",name:"Hirobumi",middleName:null,surname:"Suzuki",slug:"hirobumi-suzuki",fullName:"Hirobumi Suzuki",profilePictureURL:"https://mts.intechopen.com/storage/users/185746/images/system/185746.png",biography:"Dr. Hirobumi Suzuki received his Ph.D. in 1997 from Tokyo Metropolitan University, Japan, where he studied firefly phylogeny and the evolution of mating systems. He is especially interested in the genetic differentiation pattern and speciation process that correlate to the flashing pattern and mating behavior of some fireflies in Japan. He then worked for Olympus Corporation, a Japanese manufacturer of optics and imaging products, where he was involved in the development of luminescence technology and produced a bioluminescence microscope that is currently being used for gene expression analysis in chronobiology, neurobiology, and developmental biology. 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He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:{name:"Association for Computing Machinery",country:{name:"United States of America"}}},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:'"Politechnica" University Timişoara',institution:null},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"426586",title:"Dr.",name:"Oladunni A.",middleName:null,surname:"Daramola",slug:"oladunni-a.-daramola",fullName:"Oladunni A. Daramola",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Federal University of Technology",country:{name:"Nigeria"}}},{id:"357014",title:"Prof.",name:"Leon",middleName:null,surname:"Bobrowski",slug:"leon-bobrowski",fullName:"Leon Bobrowski",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Bialystok University of Technology",country:{name:"Poland"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"354126",title:"Dr.",name:"Setiawan",middleName:null,surname:"Hadi",slug:"setiawan-hadi",fullName:"Setiawan Hadi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Padjadjaran University",country:{name:"Indonesia"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"332603",title:"Prof.",name:"Kumar S.",middleName:null,surname:"Ray",slug:"kumar-s.-ray",fullName:"Kumar S. Ray",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Statistical Institute",country:{name:"India"}}},{id:"415409",title:"Prof.",name:"Maghsoud",middleName:null,surname:"Amiri",slug:"maghsoud-amiri",fullName:"Maghsoud Amiri",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Allameh Tabataba'i University",country:{name:"Iran"}}},{id:"357085",title:"Mr.",name:"P. Mohan",middleName:null,surname:"Anand",slug:"p.-mohan-anand",fullName:"P. Mohan Anand",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356696",title:"Ph.D. Student",name:"P.V.",middleName:null,surname:"Sai Charan",slug:"p.v.-sai-charan",fullName:"P.V. Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}}]}},subseries:{item:{id:"95",type:"subseries",title:"Urban Planning and Environmental Management",keywords:"Circular Economy, Contingency Planning and Response to Disasters, Ecosystem Services, Integrated Urban Water Management, Nature-based Solutions, Sustainable Urban Development, Urban Green Spaces",scope:"