Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
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This achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
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We are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
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Thank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
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The book provides a reference to researchers, practitioners, and students in both artificial intelligence and engineering communities, forming a foundation for the development of the field.",isbn:null,printIsbn:"978-953-51-0214-4",pdfIsbn:"978-953-51-5638-3",doi:"10.5772/2358",price:139,priceEur:155,priceUsd:179,slug:"bio-inspired-computational-algorithms-and-their-applications",numberOfPages:434,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"9025a709550b508f98bdb47a9a856d89",bookSignature:"Shangce Gao",publishedDate:"March 7th 2012",coverURL:"https://cdn.intechopen.com/books/images_new/1940.jpg",keywords:null,numberOfDownloads:53746,numberOfWosCitations:41,numberOfCrossrefCitations:42,numberOfDimensionsCitations:63,numberOfTotalCitations:146,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 18th 2011",dateEndSecondStepPublish:"June 15th 2011",dateEndThirdStepPublish:"October 20th 2011",dateEndFourthStepPublish:"November 19th 2011",dateEndFifthStepPublish:"March 18th 2012",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"11 years",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:"Edited by",kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"111444",title:"Dr.",name:"Shangce",middleName:null,surname:"Gao",slug:"shangce-gao",fullName:"Shangce Gao",profilePictureURL:"https://mts.intechopen.com/storage/users/111444/images/2292_n.jpg",biography:"Shangce Gao received the B.S. degree from Southeast University, Nanjing, China in 2005, and the M.S. and Ph. D. degrees in intellectual information systems and Innovative life science from University of Toyama, Toyama, Japan in 2008 and 2011, respectively. From 2005 to 2006, he was a technical support engineer in Wicrosoft Co. Ltd., Shanghai, China. He has received the Outstanding Academic Performance Award of IEICE Hokuriku Branch in 2008, the Outstanding Self-financed Students Abroad Award of Chinese Government from China Scholarship Council in 2009, the Outstanding Academic Achievement Award of IPSJ Hokuriku Branch in 2011, and the Outstanding Doctoral Award of University of Toyama in 2011. He is currently an associate research fellow at the Key Laboratory of Embedded System and Service Computing, Ministry of Education, Tongji University, Shanghai 200092, China. 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1. Introduction
Platinum group metals (PGMs) are a group of six elements, namely iridium (Ir), osmium (Os), platinum (Pt), palladium (Pd), rhodium (Rh) and ruthenium (Ru) [1, 2]. PGMs together with gold and silver are classified as noble or precious metals because of their high corrosion and oxidation resistance [1, 2, 3]. The world’s reserves of platinum group metals/elements are estimated at 100 million kilogrammes, of which over 80% is contained in South Africa’s Bushveld Igneous Complex [4]. Summary of the PGM reserves by country is shown in Table 1 [5]. PGMs are used in a number of industrial processes and commercial applications including automotive, jewellery, electronics, dentistry, catalysts, needles, pivots, temperature measurements, special crucibles and investments amongst others [5, 6, 7].
In South Africa, the PGM ore is mined in the western and eastern limb of the Bushveld Igneous Complex [8]. Within the Bushveld Igneous Complex, the Merensky reef, the Platreef and Upper Group 2 (UG2) reef are exploited for platinum production [1, 4, 9]. Merensky and Platreef have similar chemical and mineral composition [6, 10]. These reefs typically have fairly low contents of sulphides. UG2 differs from the two reefs in that it has low nickel and copper content [3]; compared to UG2, Merensky reef has higher amounts of chalcopyrite, pentlandite and pyrrhotite [8]. Chromite spinel can be up to 4% by mass in a UG2 concentrate, while a Merensky concentrate can have <1% by mass chromite spinel [8, 10].
A typical mineralogy of the flotation concentrate blend is shown in Table 2 [11]. Eksteen (2011) [8] has given the fractions of typical minerals in the UG2 and Merensky concentrates. The abundant gangue minerals in a typical PGM concentrate are orthopyroxene, talc, clinopyroxene and plagioclase [8]; other gangue minerals are <5% by mass [8].
Mineral
Formula
Sulphide minerals
Chalcopyrite
CuFeS2
Pentlandite
(Fe, Ni, Co)9S8
Pyrite
FeS2
Pyrrhotite
Fe1 − xSx
Gangue minerals
Alteration silicates
Hydrated minerals
Chromite spinel
FeCr2O4
Pyroxenes
(Mg, Fe)SiO3 – Ca(Mg, Fe)Si2O6
Olivine
(Mg, Fe)2SiO4
Plagioclase/feldspar
NaAlSi3O8 – CaAl2Si2O8
Quartz
SiO2
Haematite
Fe2O3
Table 2.
Sulphide and gangue mineralogy of a typical PGM concentrate [11].
3. Sources of PGM
The principal sources of PGM are sulphide and arsenide minerals such as PtAs2, PtS, Pt(AsS)2, (Pt,Pd)S, (Pt,Pd,Ni)S, RuS2 and Pd3Sb and elemental ruthenium [3, 7]. Noble metals together with cobalt (Co), copper (Cu), iron (Fe) and nickel (Ni) belong to the class of transition metals in the periodic table [6]. Geologically, PGM associates with base metal sulphides such as chalcopyrite (CuFeS2), millerite (NiS), pentlandite (Fe,Ni)9S8, pyrite (FeS2) and pyrrhotite (Fe1−xS) [3, 12, 13]. Troilite carries trace amounts of iridium, while chalcopyrite has trace amounts of Ru, Pd, Ir and Pt [13]. Gangue minerals associated with PGM-containing minerals are feldspar, biotite, plagioclase and pyroxene [12].
4. PGM ore processing: an overview
Typical process route for treating PGM ore with the approximate PGM grade in each process is shown in Figure 1 [1, 7, 9].
Figure 1.
Typical process flow diagram for PGM ore processing [9, 12].
4.1. Comminution
The PGM ore is initially treated in primary and secondary crushers after which it is sent to rod and ball milling circuits. The milled PGM ore is treated using gravity separators and flotation cells; xanthate and dithiophosphate collectors are typical reagents used for flotation at a pH of 7.5–9 [1]. A sulphide-rich PGM concentrate is produced in the flotation cells [6].
Typical composition of UG2 and Merensky flotation concentrate is shown in Table 3 [14]. A typical PGM content in the flotation concentrate is in Table 4 [9]. The UG2 concentrate has higher chrome content when compared to the Merensky as seen in Tables 3 and 4. UG2 also has higher PGM content than the Merensky concentrate. The concentrate from the flotation cells is dried and smelted to separate the sulphides from the silicates [9].
Al2O3
CaO
Cr2O3
Cu
FeO
MgO
Ni
S
SiO2
PGM (g/t)
Merensky
1.6
2.2
0.3
2.1
22.3
18.2
3.2
9
41.4
100 - 250
UG2
5.0
2.4
2.9
0.8
12.6
21.0
1.7
3.6
44.0
300 - 600
Table 3.
Typical composition of Merensky and UG2 concentrate [14].
Assay
Merensky
UG2
Platreef
PGM-4E
200
200
120
Pt-% of 4E
63.5
56.7
45.1
Pd
28.1
29.4
45.7
Rh
4.4
13.0
3.2
Au
4.0
0.9
6.0
Ir
0.6
1.6
1.0
Ru
6.8
9.6
3.5
Ni %
6.0
1.4
4.9
Cu
3.4
0.7
2.5
Co
0.15
0.05
0.2
Cr2O3
0.6
3.0
0.3
Sulphur
15-20
4-6
10-15
USD value/tonne
14009
16526
7397
Table 4.
Typical content of a PGM flotation concentrate [9].
4.2. PGM ore smelting
To separate the PGM-rich sulphides from the gangue minerals, smelting is used. Rectangular six-in-line or circular three-electrode electric furnaces are typical in the PGM industry [12]. Smelting is a high-temperature process step where the sulphides (valuable minerals) are separated from the silicates (gangue minerals). Energy required for melting the concentrate is provided by Joule heating when an electric current is passed through the resistive bath [15]. The electrodes are used for electrical connections between the power supply and the bath. Graphite electrodes are inserted into the resistive bath such that when a current is applied through the electrodes, thermal energy is generated [6, 15].
The PGM concentrate is introduced into the smelter through the feed ports situated on the furnace roof. The concentrate forms a thick bed (~400 mm) on top of the molten bath. The heat generated in the resistive bath causes the concentrate bed to melt gradually [8].
The operating temperature of the smelter at the concentrate zone can range from 600 to 900°C [16]. The liquidus temperature of base metal sulphides associated with PGMs is 850–875°C, whereas the liquidus temperature of the corresponding silicates is approximately 1350°C [16]. The sulphides in a PGM concentrate start melting at the concentrate bed since temperature at the concentrate zone can exceed the liquidus temperature of the sulphides. The silicate minerals melt when they reach the molten bath (concentrate-slag interface) [16]. The silicates and sulphides are immiscible; upon melting they form two separate layers.
The molten silicates and oxides form a fayalitic-forsteric slag layer, while the PGM-containing sulphides form a matte layer [16]. The specific gravity of matte ranges from 4.8 to 5.6, and that of slag ranges from 2.8 to 3.8 [6, 15]. Owing to the difference in specific gravities of matte and slag, the slag forms a top layer. Matte being denser than slag falls through the slag layer and settles underneath the slag. Matte consists of base metal sulphides (cobalt, copper, iron and nickel). Matte serves as a collector for the PGMs [6, 7, 14].
Operating temperature of matte and slag varies with the composition of the concentrate [8]. Typical smelter operating temperature for matte varies from 1380 to 1600°C, and that of slag varies from 1500 to 1680°C [8].
The molten slag and matte are tapped out of the smelter through the tap holes situated at the sidewall of the furnace. After tapping, the matte either can be fed directly to the converters as tapped or can be granulated before the conversion step; matte treatment varies with the producers.
4.2.1. Industrial PGM-furnace matte
Anglo American Platinum (Amplats), Impala Platinum (Implats) and Lonmin are three major producers of PGM in South Africa [9]. Typical compositions of matte from selected smelters are shown in Table 5. Matte from different smelters seems to have comparable amounts of major components (Cu, Fe, Ni and S). The slight difference is that the amount of iron in Amplats matte is slightly higher than the iron in a Lonmin matte (Table 5).
Co
Cr
Cu
Fe
Ni
S
Amplats-Waterval
0.5
0.5
9.0
41.0
17.0
27.0
Lonmin-Merensky/UG2
0.5
0.2
9.7
37.0
17.0
28.0
Lonmin-UG2
0.5
0.3
9.8
35.0
17.0
28.0
Table 5.
Typical chemical composition of industrial matte from selected smelters (% by mass) [12].
4.2.2. Industrial PGM-furnace slag
Gangue minerals associated with PGM-containing minerals are feldspar, biotite, plagioclase and pyroxene ([Ca,Na]Al1–2Si3–2O8) [12]. During smelting these gangue minerals form a slag that is a silicate rich phase. Typical composition of a PGM-furnace slag from different smelters is shown in Table 6 [12]. The oxide compounds in Amplats and Lonmin-Merensky slag are comparable; Lonmin-UG2 slag has higher Cr2O3, CaO and MgO; and its FeO content is significantly lower when compared to that of the slag from Amplats and Lonmin-Merensky ore.
Al2O3
CaO
Co
Cr2O3
Cu
FeO
MgO
Ni
S
SiO2
Amplats-Waterval
3.3
6.4
0.1
0.8
0.1
31.0
15.0
0.2
0.5
46.0
Lonmin-Merensky
2.0
9.8
0.1
1.2
0.1
28.0
19.0
0.2
0.0
44.0
Lonmin-UG2
3.9
13.0
0.0
2.4
0.1
9.2
22.0
0.1
0.0
47.0
Table 6.
Typical chemical composition of industrial slag from different smelters (% by mass) [12].
4.3. Converting
After smelting, the furnace matte is treated in Pierce-Smith converters or Ausmelt process where iron sulphide is oxidised to ferrous oxide and sulphur is oxidised to sulphur dioxide [9]. Sulphur dioxide is removed as an off-gas, and iron oxide is removed as a fayalitic slag. The slag phase of the converter contains significant amounts of entrained PGM and is recycled to the smelting furnace to recover the entrained PGM. The converter matte is cooled, milled and treated in base metals refinery (BMR) [1, 9].
4.4. Purification
Typical hydrometallurgical processes used for PGM purification are as follows: dissolution-precipitation (pressure oxidation leach), solvent extraction and ion exchange and molecular recognition technology [17]. Pressure oxidation leach is a typical hydrometallurgical process used to separate base metals from the PGM residue. The base metals are leached, while the PGMs remain in the residue. The PGM residue is sent to a precious metal refinery where various solution extraction and precipitation methods are used to separate individual metals [1]. Solvent extraction is another method by which PGMs can be separated from the base metals [7].
5. Operational challenges facing PGM industry
South Africa is faced with increasing cost of electricity which has direct impact on the energy-intensive processes such as smelting [1, 18]. South African PGM producers generally process a Merensky concentrate where available; otherwise, the Merensky and UG2 concentrates are blended together to achieve the required feed composition for the smelter. In recent years, the depletion of the Merensky reef has forced the PGM producers to mine the UG2 reef that has up to 60% chromite. As a consequence, the concentrate from the floatation cells has high chrome content than the amount that the smelters are designed to handle. In reducing conditions, the operating temperature limits the solubility of Cr2O3 in a typical slag. At 1450–1650°C the solubility of Cr2O3 in slag is limited to 1.8% by mass. As such the smelters have battled with numerous challenges owing to the treatment of a high chrome concentrate [9, 19].
5.1. Challenges associated with smelting high chromite concentrate
The challenges associated with high chrome feed to the smelter are the following [19]:
Formation of chromite spinels which are insoluble in slag.
Chromite spinels have high melting points as such they increase the liquidus temperature of the slag and they lower the fluidity of the slag [19].
Chromite spinels increase the overall temperature of the constituents (slag and matte) [8].
When the matte temperature is above the liquidus temperature of the slag freeze-lining, the matte dissolves the freeze-lining; this leads to corrosion of the refractories by corrosive PGM melt [8].
There are FeO- and CrO-based spinels; the proportion of Fe and Cr in the spinel may vary, as such there are spinels that are heavier than the matte, while other spinels are slightly lighter than matte. Spinels which are denser than matte settle on the hearth; the accumulation of spinels on the hearth reduces the volume of the furnace [8].
Spinels with intermediate density form a ‘mushy’ layer at the slag-matte interface; this leads to the entrainment of matte in slag [8].
High chrome decreases electrical conductivity of the bath leading to electrical control problems in the furnace [19].
Higher chrome levels affect the matte temperatures during conversion step (matte temperatures above 1355°C have been observed); this causes damage to the refractory lining. Cold dope (revert) is normally used to lower the temperature of the matte during conversion [16, 19].
A number of approaches have been investigated to deal with the chrome problem. The following actions have eased chromite problem in the smelters:
Deep electrode immersion operating at high power densities causes sufficient mixing which keeps the solids in suspension [8, 21], but high power densities adversely affect the refractory life. To minimise the effect of high power input on the refractory life of the sidewall lining, the phase voltage is increased without increasing the current levels [19].
Some producers stopped recycling the converter slag to the furnaces since the converter slag has high chrome content [19, 20].
The flux addition in the furnace was discontinued since lower CaO levels increased the solubility of the chromite in the slag [19, 20].
The control of furnace inputs and control of furnace parameters (power, furnace availability) are essential in controlling chrome content [19].
Selective reduction improves the solubility of chromium in the slag [20].
Tapping out the intermediate layer intentionally [22].
Decreasing the chromium input to the smelters [20].
Another innovation able to manage chrome-rich ores is the ConRoast process. This process involves removing and capturing sulphur from the concentrate prior to smelting in a DC arc furnace. Roasting a concentrate makes smelting more environmentally friendly; it also enables furnaces to accept any proportion of chromite, resulting in more efficient and cost-effective platinum production [9, 23].
5.2. Premature failure of refractory lining
Due to high operating temperatures (1350 to >1600°C) [8] associated with PGM smelting, the smelter has to be lined with refractories at the hot face. To prolong the service life of the refractories, sufficient cooling of the refractories is required at the cold face of the refractory wall. Copper waffle coolers are typically used in the cold face of the refractories to extract heat away from the refractories [24]. Due to high operating temperature and corrosiveness of the PGM melt, premature failure of the waffle copper coolers has been experienced in PGM smelters [24] in the upper sidewall region. Failure of waffle copper coolers causes explosions, loss of production and costs associated with furnace rebuild. The failure of waffle copper coolers was preceded by the consumption of conventional refractory bricks (MgOx-CrOx) which were used to form the furnace lining. The refractory brick (MgOx-CrOx) had low resistance to chemical attack by liquid PGM melt. To prevent the occurrences of copper cooler failures, conventional bricks have been replaced by the graphite blocks in recent designs of PGM smelter refractory walls [25]. Graphite blocks are only applied at the hot face of the upper sidewall (against the concentrate and the slag zone).
With the graphite block lining, a frozen protective skull forms at the hot face of the refractory. The formation of the protective skull is attributed to the efficient cooling of the refractory wall by waffle coolers. The frozen skull is the melt that solidified due to the surface temperature of the graphite that was lower than the liquidus temperature of the melt [25].
Graphite blocks have increased the service life of the waffle copper coolers through the formation of a protective layer. However, high infiltration of melt is still observed at the matte-slag tidal zone. This is a challenge that still needs to be addressed; currently, conventional bricks or monolithics are used at lower sidewall of the PGM smelter refractory. It is desired to extend the graphite blocks to the lower sidewall of the PGM smelter refractory wall against the matte zone [25]. It is envisaged that using carbon-based refractory at the hot face of the matte zone (lower sidewall) will improve the service life of the furnace lining in PGM smelters [25].
6. Opportunities in PGM processing
The PGM industry faces challenges with increasing chrome content in the feed and premature failure of refractory lining in the smelter. Alternative ways to process the PGM have become attractive due to the challenges associated with the conventional smelting process [1, 18]. A hydrometallurgy (Kell) process has been probed as an alternative to smelting PGM. The Kell process has three stages: stage 1 is the leaching of base metal sulphides in an acidic sulphate medium (pressure oxidation); stage 2 is roasting of the residue from stage 1; and stage 3 is atmospheric leaching of PGMs in a chloride media. The leached precious metals are further treated in refineries to recover metals [18]. Other hydrometallurgical routes have been discussed in Ref. [1]. These hydrometallurgical processes have advantages over the smelting process since they reduce the operating costs drastically [1]. However, the alternative hydrometallurgical routes of processing PGMs have not yet been commercialised [1].
7. Conclusions
In this chapter, an overview of PGM processing has been presented. The conventional smelting process has challenges with high chromium feed, premature failure of refractory lining and increased operating cost associated with increasing cost of electricity in South Africa. The Kell process is an alternative way to process a PGM concentrate, and it has a number of advantages such as less energy consumption, less energy cost, less electricity consumption, less CO2 emissions and no restriction on chrome content of feed. Other hydrometallurgical routes have been investigated, but none has been commercialised yet.
\n',keywords:"platinum group metals, chrome, smelting, UG2, Merensky",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/58968.pdf",chapterXML:"https://mts.intechopen.com/source/xml/58968.xml",downloadPdfUrl:"/chapter/pdf-download/58968",previewPdfUrl:"/chapter/pdf-preview/58968",totalDownloads:2717,totalViews:966,totalCrossrefCites:1,totalDimensionsCites:2,totalAltmetricsMentions:0,introChapter:null,impactScore:1,impactScorePercentile:74,impactScoreQuartile:3,hasAltmetrics:0,dateSubmitted:"October 2nd 2017",dateReviewed:"December 18th 2017",datePrePublished:"February 21st 2018",datePublished:"July 4th 2018",dateFinished:"January 23rd 2018",readingETA:"0",abstract:"About 80% of the worlds’ reserves for platinum group metals (PGMs) are in South Africa’s Bushveld Igneous Complex. Processing of PGM involves comminution, flotation, smelting, converting, base metals refinery and precious metals refinery. Due to increasing chrome content in the feed and the challenges associated with operating high chrome feed, alternative routes to smelting of PGM are being investigated. Some hydrometallurgical routes have been proposed. However, none of the reported potential routes have yet been commercialised.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/58968",risUrl:"/chapter/ris/58968",book:{id:"6282",slug:"noble-and-precious-metals-properties-nanoscale-effects-and-applications"},signatures:"Bongephiwe Mpilonhle Thethwayo",authors:[{id:"224083",title:"Dr.",name:"Bongephiwe",middleName:null,surname:"Thethwayo",fullName:"Bongephiwe Thethwayo",slug:"bongephiwe-thethwayo",email:"77mpilot@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Geology",level:"1"},{id:"sec_3",title:"3. Sources of PGM",level:"1"},{id:"sec_4",title:"4. PGM ore processing: an overview",level:"1"},{id:"sec_4_2",title:"4.1. Comminution",level:"2"},{id:"sec_5_2",title:"4.2. PGM ore smelting",level:"2"},{id:"sec_5_3",title:"Table 5.",level:"3"},{id:"sec_6_3",title:"Table 6.",level:"3"},{id:"sec_8_2",title:"4.3. Converting",level:"2"},{id:"sec_9_2",title:"4.4. Purification",level:"2"},{id:"sec_11",title:"5. Operational challenges facing PGM industry",level:"1"},{id:"sec_11_2",title:"5.1. Challenges associated with smelting high chromite concentrate",level:"2"},{id:"sec_12_2",title:"5.2. Premature failure of refractory lining",level:"2"},{id:"sec_14",title:"6. Opportunities in PGM processing",level:"1"},{id:"sec_15",title:"7. Conclusions",level:"1"}],chapterReferences:[{id:"B1",body:'Safarzadeh MS, Horton M, Van Rythoven AD. Review of recovery of platinum group metals from copper leach residues and other resources. Mineral Processing and Extractive Metallurgy Review. 2018;39(1):1-17'},{id:"B2",body:'Glaister BJ, Mudd GM. The environmental costs of platinum–PGM mining and sustainability: Is the glass half-full or half-empty? Minerals Engineering. 2010;23(5):438-450'},{id:"B3",body:'Xiao Z, Laplante AR. Characterizing and recovering the platinum group minerals – A review. Minerals Engineering. 2004;17(9):961-979'},{id:"B4",body:'Junge M, Wirth R, Oberthür T, Melcher F, Schreiber A. Mineralogical siting of platinum-group elements in Pentlandite from the Bushveld complex, South Africa. Mineralium Deposita. 2015;50(1):41-54'},{id:"B5",body:'Jewell S, Kimball SM. Mineral Commodity Summaries 2015. U.S. Geological Survey. Reston, Virginia: CreateSpace Independent Publishing Platform; 2015;196:120-121'},{id:"B6",body:'Jones RT. An overview of Southern African PGM smelting, nickel and cobalt 2005: Challenges in extraction and production. In: 44th Annual Conference of Metallurgists, Calgary, Alberta, Canada: Canadian Institute of Mining, Metallurgy and Petroleum. 21-24 August 2005. pp. 147-178'},{id:"B7",body:'Hayes PC. Process Principles in Minerals & Materials Production. 3rd ed. Australia: Hayes Publishing CO; 2003. pp. 278-279'},{id:"B8",body:'Eksteen JJ. A mechanistic model to predict matte temperatures during the smelting of UG2-rich blends of platinum group metal concentrates. Minerals Engineering. 2011;24(7):676-687'},{id:"B9",body:'Cramer LA. What is your PGM concentrate worth? In: Third International Platinum Conference, ‘Platinum in Transformation’, Johannesburg, South Africa: South African Institute of Mining and Metallurgy; 2008. pp. 5-9'},{id:"B10",body:'Nell J. Melting of platinum group metal concentrates in South Africa. Journal of the South African Institute of Mining and Metallurgy. 2004;104(7):423-428'},{id:"B11",body:'Andrew NJ, van Beek B, Lexmond A, Zietsman JH. Effect of Feed Composition Fluctuations on a Platinum Furnace Energy Balance and Slag Temperature. The Southern African Institute of Minng and Metallurgy, Pyrometallurgical Modelling-Principles and Practices, Kempton Park, South Africa, 4-5 August 2014. pp. 117-126'},{id:"B12",body:'Jones RT. Platinum smelting in South Africa. South African Journal of Science. 1999;95:525-534'},{id:"B13",body:'Cabri LJ, Rudashevsky NS, Rudashevsky VN. Current approaches for the process mineralogy of platinum-group element ores and tailings. In: Ninth International Congress for Applied Mineralogy ICAM. Geological Society of India. 2009. pp. 9-17'},{id:"B14",body:'Liddell KS, McRae LB, Dunne RC. Process routes for beneficiation of noble metals from Merensky and UG-2 ores. Mintek Review. 1986;4:33-44'},{id:"B15",body:'Habashi F. Textbook of Pyrometallurgy. Canada: Métallurgie Extractive Québec; 2002. pp. 237-242'},{id:"B16",body:'Eksteen JJ, Van Beek B, Bezuidenhout GA. Cracking a hard nut: An overview of Lonmin’s operations directed at smelting of UG2-rich concentrate blends. Journal of the Southern African Institute of Mining and Metallurgy. 2011;111(10):681-690'},{id:"B17",body:'Bezuidenhout GA, Eksteen JJ, Akdogan G, Bradshaw SM, De Villiers JPR. Pyrometallurgical upgrading of PGM-rich leach residues from the western platinum base metals refinery through roasting. Minerals Engineering. 2013;53:228-240'},{id:"B18",body:'Liddell K, Newton T, Adams M, Muller B. Energy consumptions for Kell hydrometallurgical refining versus conventional pyrometallurgical smelting and refining of PGM concentrates. In: The 4th International Platinum Conference, Platinum in Transition ‘Boom or Bust’. Johannesburg, South Africa: The Southern African Institute of Mining and Metallurgy; 2010. pp. 181-186'},{id:"B19",body:'Coetzee V. Common-sense improvements to electric smelting at impala platinum. Journal of the Southern African Institute of Mining and Metallurgy. 2006;106(3):155-164'},{id:"B20",body:'Hundermark RJ, Mncwango SB, de Villiers LPS, Nelson LR. The Smelting Operations of Anglo American’s Platinum Business: An Update, Southern African Pyrometallurgy 2011. Johannesburg: Southern African Institute of Mining and Metallurgy; 6-9 March 2011. pp. 295-307'},{id:"B21",body:'Liddell KS, Adams MD. Kell hydrometallurgical process for extraction of platinum group metals and base metals from flotation concentrates. Journal of the Southern African Institute of Mining and Metallurgy. 2012;112(1):31-36'},{id:"B22",body:'Barnes AR, Newall AF. Spinel Removal from PGM Smelting Furnaces. Southern African Pyrometallurgy, 5-6 March 2006. Johannesburg, South Africa: Southern African Institute of Mining & Metallurgy; 2006. pp. 77-88'},{id:"B23",body:'Jones RT, Geldenhuys IJ. The pros and cons of reductive matte smelting for PGMs. Minerals Engineering. 2011;24(6):495-498'},{id:"B24",body:'McDougall I, Eksteen JJ. Sidewall design to improve lining life in a platinum smelting furnace. In: International Smelting Technology Symposium (Incorporating the 6th Advances in Sulphide Smelting Symposium). Warrendale, PA: TMS (The Minerals, Metals & Materials Society); 2012. pp. 47-54'},{id:"B25",body:'Thethwayo BM. Sulphidation of copper coolers in PGM smelters. [MSc thesis]. South Africa: University of Pretoria; 2010'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Bongephiwe Mpilonhle Thethwayo",address:"77mpilot@gmail.com",affiliation:'
University of Johannesburg, Johannesburg, South Africa
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1. Introduction
Calcium and phosphate are critical to skeletal mineralization; while ionized calcium is essential for neuromuscular function and serves as a signaling molecule to communicate and drive intracellular processes. Although, only about 1% of total body calcium and 15% of total body phosphorus is in circulation, the ionized fractions of circulating calcium and phosphate are tightly regulated by the interplay of several hormones to keep their status of homeostasis in response to environmental cues and the physiological needs [1].
PTH and 1,25-dihydroxy vitamin D are the major regulators of calcium metabolism, while PTH and EGF 23 and its cofactor, klotho, work concertedly to control renal excretion of phosphorus and maintain phosphate balance. The complex system is at play to keep these hormones in check in the healthy, while this intricate control mechanism is disrupted in diseases due to the hormone excess/deficiency or loss of the metabolite feedback control such as in patients with parathyroid gland dysfunction or chronic kidney diseases. Therefore, timely and accurately assessing, monitoring, and profiling of these hormones and the important metabolites is essential for the clinicians to understand the degree of calcium and phosphate imbalance when they evaluate the related disorders such as hypoparathyroidism, various forms of hyperparathyroidism, and chronic kidney disease-induced mineral and bone disorder (CKD-MBD) [2, 3].
PTH measurement has been used in the diagnosis and treatment of disorders of calcium/phosphate metabolism because of its predominant role in maintaining the circulating ionized calcium within a very tight concentration range, and in regulating the urinary excretion of phosphorus. PTH measurement is a valuable tool for diagnosing primary and secondary hyperparathyroidism (SHPT). It is also used as a surrogate biomarker to guide the management strategies for CKD patients presenting with systemic mineral and bone disorders (CKD-MBD) and monitoring its progression.
The presence of various circulating forms of PTH and its metabolites, the inter-assay variability and the presence of many variables from sample collection to the test reporting pose significant challenges for accurate PTH quantitation in clinical laboratories and the interpretation of PTH results by clinicians.
2. Evolution of PTH assays
Circulating PTH is a heterogeneous population consisting of full-length PTH (84 amino acids, with a molecular of ~9500 Da) and various sizes of proteolytic C-terminal, N-terminal, and mid-molecule metabolites [4]. In healthy individuals, predominant C-terminal PTH fragments typically started at amino acid position 34, 37, 38, or 45 [5]; a subtype of C-PTH, known as non-1-84 or PTH (7-84), usually starts at amino acid position 4, 7, 8, 10, or 15 with the major fragment presumably starting at position 7 [6, 7]. Full-length PTH (1-84) and N-terminal PTH fragments have very short half-lives (2–4 min), while the C-terminal PTH fragments have a half-life of several hours and even longer in CKD patients with decreased renal clearance [8]. The half-life of PTH (7-84) fragments is longer, ranging from 8.1 to 24.0 min [9]. It was shown that PTH (7-84) fragments are released from the parathyroid gland directly in healthy individuals, but proportionally increase relative to total circulating PTH due to bioaccumulation in patients with CKD [10].
The first C-terminal PTH radioimmunoassay was described by Berson et al. [11]; this and the subsequent first-generation PTH assays employed a single polyclonal antibody against epitopes that were located within the C-terminal part of PTH and thus detected both PTH (1-84) and all C-PTH fragments. It was found that PTH (1-84) and C-terminal PTH fragments accounted for 20% and 80% of the circulating PTH respectively in healthy adults when measured by the first-generation PTH assay [12]. Meanwhile, in CKD patients, the proportion of measured C-terminal PTH fragments increased to 95% of circulating PTH [13]. The first generation PTH RIA assay is time-consuming and lacks specificity, especially in CKD patients and thus was totally replaced by more specific second-generation sandwich assays.
Nichols Diagnostics developed a two-site immunoradiometric assay (IRMA) for measuring PTH in 1987; this assay uses a capture antibody directed against the 39-84 C-terminal epitope region and a signaling antibody directed towards the 13−4 N-terminal epitope region to form antibody-PTH-antibody complex and thus greatly improved sensitivity and specificity of the PTH quantitation [14].
Subsequently, non-radioactive labeling assay formats (ELISA, chemiluminescent, and electrochemiluminescent methods) were brought forth and operated in automated immunoanalyzers in clinical laboratories of all sizes, which became and still remain to be the most widely-used PTH assays to date. These second-generation assays were collectively known as “intact” PTH assays, for it was thought that they measure only the full-length PTH (1-84). However, it was uncovered later that the “intact” PTH assays still cross-react with PTH (7-84) fragments (ranging from 50% to 100%), and thus overestimated PTH concentration in CKD patients [15].
To improve the diagnostic accuracy, the first third-generation “biointact,” (also known as “bioactive” or “whole”) PTH (1-84) assay, was advanced by Scantibodies Laboratories and became available as an exoteric testing service since 1999. It is an immunochemiluminometric assay with a signaling antibody directed against the epitope within the first 4 amino acids at the very N-terminus of full-length PTH [16]. More recently, non-radioactive automated and FDA-cleared third-generation assays were marketed by several manufacturers including DiaSorin, Tosoh, Fujirebio, Roche, and bioM´erieux [17]. Since third-generation assays have higher specificity to PTH (1-84) and won’t cross-react with C-PTH, the measuring values are approximately 50–70% of those measured by the second generation PTH assay in patients with CKD and approximately 15% lower than those in persons without CKD. Because second generations assays have been used for decades and are still widely in use, this inter-generation assay difference complicates the test interpretation and the adoption of the new assays. It was expected that the use of the third-generation assays can resolve the issue of cross-reactivity with non-functional PTH fragments (i.e., PTH 7-84). However, subsequent studies revealed the complexity of PTH physiology that was undetected by the older PTH assays. In addition to the full-length PTH (1-84), the third-generation “biointact” PTH also reacted with a new form of N-terminal PTH (N-PTH) that is not recognized by most second-generation PTH assays. Further investigation showed that posttranslational phosphorylation at serine position 17 of the PTH (1-84) molecule prevent (or reduces the binding affinity of) the signaling antibody in most second-generation assays from binding to its epitope in the phosphorylated N-PTH. N-PTH accounts for 4–8% versus 15% of circulating PTH measured by the third generation PTH assays in healthy versus in patients with CKD [16, 18].
3. Unresolved problems with PTH assays
3.1 Inter-assay variability
Currently, automated second-generation and third-generation PTH assays are employed in clinical laboratories for PTH measurement. Current second-generation assays provide convenient and relatively reliable methods (intra-assay imprecision <10 %) for PTH measurement [19]. However, different PTH assays from various assay manufacturers measure different types and amounts of the circulating PTH forms depending on the specificity of the antibodies used to construct the assay, which led to great inter-assay variability and inconsistent results among the PTH measurements when the now-obsolete Allegro PTH intact assay served as the reference [20, 21, 22]. In a more recent study, a performance comparison among six currently-existing second-generation assays was made. Imprecision was evaluated using three concentrations of commercial quality control materials, while inter-assay variability was assessed by paired comparisons using 203 serum and 193 EDTA plasma samples from healthy individuals. The results showed that the imprecision (i.e., total coefficients of variation) were between 1.1% and 10.9% and there was a good correlation for all methods overall but the considerable bias was observed between methods, the Bland-Altman plots revealed that the between assay differences were between +1.6% to −36.3%, influenced by both assays and sample types used [23].
The results of third-generation PTH assays are approximately 50–70% of those measured by the intact PTH assay in patients with CKD and approximately 15% lower
than those in persons without CKD [16, 18]. The automated third-generation assays are calibrated against the WHO 95/646 Standard and therefore displayed significantly improved inter-method agreements [24, 25]. However, the incompatibility in measurement to that of the widely-used second generation assays affect the interpretations of the method validation and may contribute to its slow adaptation to clinical laboratories in general.
3.2 Aggravating heterogeneity of circulating PTH in the disease states
The pathological changes in calcium and phosphate status and the progressive loss of feedback control in the calcium and phosphate regulatory system in hemodialyzed patients further exacerbate the problem of assay variability. A systematic performance evaluation of 15 commercial immunoassays with 47 serum pools from dialysis patients, reported by Souberbielle et al. [21] in 2006, showed great inter-assay variability among the tested PTH assays, moreover, the discrepancies of measured values in some assays compared to the then “gold-standard” Allegro PTH intact assay are unacceptable, and may cause patient harm when the discrepant results were used to make therapeutic decisions. This raised the alarm in the dialysis community to question the reliability of the PTH testing and resulted in many more investigations on these critical issues. A recent position paper issued by the IFCC Committee for Bone Metabolism tabulated 23 major assay comparison studies using samples from CKD or hemodialysis patients (published between 2005 and 2018) [17]. The results reaffirmed that existing between-method differences in PTH measurements did not improve much and likely have treatment implications.
As described earlier, third-generation assays cross-react with a phosphorylated form N-PTH was overproduced in some patients with parathyroid carcinoma and severe primary hyperparathyroidism (PHPT) [26, 27]. In these cases, PTH determination with the third generation assay will have a value greater than the one with the second-generation assay. The inverted third/second PTH ratio is therefore proposed as a screening or monitoring tool for parathyroid cancer [28]. However, the inter-assay variability makes it challenging to define a generally acceptable cutoff for validating the proposed clinical utility unless the problem of analytical variability is effectively addressed.
3.3 Issues of concern related to testing procedures
3.3.1 Pre-analytical phase: Sample stability, sample type, and sampling time
The unstable nature of PTH makes it essential to optimize pre-analytical parameters, including specimen type, sampling time, and storage conditions, which have all been thoroughly investigated. After a systematic review conducted under the auspice of IFCC PTH Working Group, the following evidence-based recommendations are made by IFCC: [29, 30].
For samples collected with EDTA tubes, the plasma must be separated from the cells within 24 hours of venipuncture. Samples should be kept at 4°C and analyzed within 72 hours of venipuncture.
For serum samples, the serum must be separated from the cells as soon as possible, and PTH is analyzed within 3-4 hours of venipuncture.
Central venous PTH concentrations were higher compared to peripheral venous PTH concentration, therefore, in patients undergoing hemodialysis or parathyroidectomy, if the blood samples were collected via central line or central vein; the collected tube, as well as the test report, should explicitly state the collection site and whether they are peripheral or central venous concentrations.
PTH follows a circadian rhythm, exhibiting a nocturnal peak, a mid-morning nadir, and a smaller afternoon peak. Therefore, it is suggested that samples for PTH measurement should be collected between 10:00 and 16:00, preferably in the morning with an overnight fast. Other known biological variations include the fact that PTH level increases with age and BMI, and is generally higher in African Americans than in Caucasians.
PTH has longer stability in EDTA tube at room temperature than in serum tube, thus delayed centrifugation to allow blood clotting is not needed; however, it is important in clinical practice that PTH measurement be accompanied by a concomitant calcium value. Since calcium (and bone-alkaline phosphatase) cannot be measured in EDTA plasma, PTH and calcium are to be measured in the same serum tube and therefore may be a preferred option for practical reasons. In two recent reports, PTH values obtained from the rapid serum tubes were found to be decreased compared to those from the serum separator tubes (SSTs) [31, 32].
So far, there is no reported data on the comparison of relative PTH stability using second-generation versus third-generation assays. Such study is valuable in providing further insight into the ex vivo stability/vulnerability of each type of PTH molecule.
All immunometric assays are inherently prone to interference from heterophilic antibodies (i.e., human idiotypic antibodies that interact with assay antibodies raised from animals). Such interference can lead to diagnostic errors and may cause harm to patients as consequence. Assay manufacturers have introduced effective blockers to the assay reagent as a preventive measure against heterophilic antibody interference; however, increasing use of modified monoclonal mouse antibodies as therapeutics in recent years makes heterophilic antibodies interference a special concern in the patients who receive such treatment. Clinicians and laboratorians should keep open communication when the testing results did not match the clinical picture of the patients. Laboratorians should offer adequate confirmatory measures and be able to interpret the investigative results timely and correctly to avoid the spurious results being used to make important clinical decisions for patient management [33].
3.3.3 Post-analytical phase: reference ranges
Since a great inter-assay variability is still present among current commercial PTH assays, there also exists a significant difference for the reference ranges provided by the manufacturers. This makes validation of the PTH assay in use an indispensable but tedious and challenging job. The first and foremost is the selection of the reference population; The eGFR, serum calcium, and 25[OH]D values of the candidate samples should be determined to only include those within reference ranges, especially the 25[OH]D level should be >30 ng/mL [34, 35]. The reference ranges should be established for each sample locally used. If types of collection tubes differ among the collection sites, it is advisable to perform a comparison study to determine if the reference range should be revised to accommodate the difference. In high latitude areas, the effect of seasonal variation in 25[OH]D levels may need to be taken into consideration in designing the validation study for establishing the local reference range for PTH assay.
3.4 Inability to discern oxidized from non-oxidized PTH by current clinical PTH assays
Loss of biological activity of oxidized PTH in vitro was observed as early as 1934, it was later showed that oxidation of two methionine residues at positions 8 and/or 18 within the receptor-binding domain results in the altered three-dimensional conformation of PTH, which in turn results in greatly reduced affinity to PTH receptor [36]. Other in vitro studies also provide evidence that oxidized PTH does not stimulate cAMP-mediated signal after binding to its cellular receptor and thus lost the ability to activate muscle contraction, nor can it stimulate mouse calvarial bone cells to increase alkaline phosphatase activity, which indicates that excessive oxidative stress may disrupt calcium and phosphate homeostasis through oxidation of PTH [37].
There is plenty of experimental evidence to support the increase of oxidative stress in patients with CKD due both to the depletion of anti-oxidants and increase of reactive oxidative species (ROS) production; increasing oxidative stress is also shown to be associated with complications such as hypertension, atherosclerosis, and anemia and therefore may contribute to the accelerated disease progression and mortality in CKD [38]. However, none of the current second-and third-generation assays can discern oxidized from non-oxidized PTH until recently due to the lack of appropriate analytical tools for investigation.
Hocher et al. developed a two-step method to measure the non-oxidized PTH; the oxidized PTH molecules were first removed by an immunoaffinity column with monoclonal antibodies specifically against the oxidized human PTH (1-34) fragment, the remaining non-oxidized PTH was then measured by Roche second-generation PTH assay. The method was applied to analyze 17 hemodialyzed samples and revealed a substantial but variable portion (70−90%) of the total PTH was in oxidized form for all samples tested [39]. These tools enable the researchers to assess iPTH, non-oxidized PTH and oxidized PTH simultaneously using the same parameters in clinical research settings to address the clinical association of oxidized PTH with the progression of CKD [40, 41]. However, the results from these studies are not conclusive.
The inherent problems of the analytical procedure are a concern. First, the ex vivo oxidation after sample collection cannot be ruled out; second, the recovery of non-oxidized PTH after the immunoaffinity column removal of oxidized PTH is unknown in clinical samples, and most troubling of all, iPTH assays has not been standardized yet, it is known that some of the iPTH assays use a signaling antibody that is raised against the epitope close to the second oxidation site (methionine at position 18) in PTH; the avidity of such signaling antibody may be changed by the oxidation of PTH. Therefore, replacing second-generation intact PTH with a more specific third-generation PTH (1-84) assay, introducing the spiked internal control to calculate recovery after column treatment, and devising standard operating procedures to minimize and evaluate the extent of ex vivo oxidation will improve the reliability of this assay. For now, the non-oxidized PTH is not ready for clinical use unless all the issues described above are appropriately addressed.
3.5 Clinical implications of the problematic PTH measurements
Lack of a common PTH reference range not merely cause inconvenience, but it also affects results interpretation, and possibly clinical management, especially for monitoring long-term changes of PTH level if patients are not able to use the same health care facilities. More importantly, intraindividual biological variability of PTH is known to increase in hemodialysis patients. The negative impact of PTH assay variability on the management of patients with CKD and hyperparathyroidism is especially troublesome.
3.5.1 Clinical practice guidelines for PTH measurement in CKD-MBD
In 2003, National Kidney Foundation—Kidney Disease Outcomes Quality Initiative (KDOQI) published a guideline that recommended maintaining a target range of 150–300 pg/mL for intact PTH concentrations in stage 5 CKD patients to reduce the mortality related to CKD-MBD. However, the recommendation was based on the comparison of PTH measurements using Allegro iPTH (now obsolete) with the gold standard–bone biopsy, before the problem of inter-assay variability being revealed. A later study showed that iPTH (measured by Immulite DCP assay) levels less than 150 pg/ml for identifying low turnover and greater than 300 pg/ml for high turnover presented a positive predictive value of 83% and 62%, respectively, moreover, in patients achieving the target iPTH levels, 88% had low turnover diseases [42]. The great inter-assay variability is a likely contributing factor to the poor results and indicated the misclassifications may cause harmful clinical outcomes [21].
In one study conducted by the United Kingdom National External Quality Assessment Service (UK-NEQAS), a 4.2-fold difference between highest and lowest measured PTH concentrations were observed using five commonly-used second-generation assays when testing EDTA plasma from 21 hemodialysis patients. In a subsequent study, 98 patient samples were tested by the same iPTH assays to derive assay-specific target values based on Passing and Bablok regression against Roche Elecsys E170 assay which gave the closest results to target values recommended by clinical guidelines. By applying the corrected assay-specific target values, the misclassifications of bone turnover reduced from 53% to 12% [43].
The Kidney Disease Improving Global Outcomes (KDIGO) 2009 Guidelines for the Diagnosis, Evaluation, Prevention and Treatment of CKD-MBD expanded the scope and refined the recommendations to assist clinicians in treating patients with CKD Stages 3–5 who are on dialysis. Aware of the problem of inter-assay variability, this guideline avoids the use of absolute PTH values but suggests hemodialyzed patients maintain PTH levels between two and nine times the upper normal limit (ULN) of the assay used and emphasize on trending the changing pattern rather than the value per se. PTH values above the target suggest high bone turnover bone disease with a specificity of 86%, while PTH levels below the target value suggest low bone turnover with a sensitivity of 66%. In its recent update (July 2017), targets for CKD-MBD biomarkers, including PTH, remain unchanged [44]. As mentioned earlier, 25[OH]D status has a substantial influence on physiological PTH level, but PTH assay reference ranges offered by the vendors might be established with samples of poor 25[OH]D status. Recent studies reported that the upper reference range for PTH established with a reference population with normal GFR and calcium levels, and a 25[OH]D level >20 ng/mL is significantly lower than the reference range provided by the manufacturers [35, 45, 46]. Cavalier et al. found that applying KDIGO guideline PTH target ranges using reference ranges established in a vitamin D replete healthy control population would reduce the percentage of misclassification of bone turnover in dialyzed patients to 16% (versus 36% using vendor-established reference range) [34].
3.5.2 PTH assay incompatibility and the diagnosis of PHPT
Comparison studies compared Nichols iPTH versus Bio-intact PTH assays and Scantibodies Laboratory’s Total versus Whole PTH assays showed high diagnostic sensitivity for both second-and third-generation PTH assays (89−97%), which provided evidence that both types of PTH assays are valuable tools in diagnosing PHPT and provide comparable results [47].
It is essential, as described earlier, to use a vitamin D-replete population to establish the reference range for PTH; the diagnostic accuracy (sensitivity and specificity) for PHPT was shown to be improved in a vitamin D-replete population [46, 48]. However, there is debate over using sufficiency level (30 ng/mL) or insufficiency level (20 ng/mL) as the threshold. So far, there are still no established reference intervals for second-and third-generation PTH assays using large vitamin D-replete population cohorts; subjects with hypercalcemia and a PTH persistently within the upper reference range should be considered “asymptomatic” PHPT and closely monitored [49].
3.5.3 Assay-dependent rate change in intra-operative PTH testing
Because PTH (1-84) has a very short half-life (~5 min), measuring PTH concentrations during parathyroidectomy can inform surgeons whether the pathological parathyroid tissue has been removed completely. A 50% decline of PTH compared with the preoperative level is commonly used to define treatment success. Since second-generation assays cross-react with C-terminal fragments with a longer half-life, it is reasonable to think third-generation assays will perform better for intraoperative PTH monitoring. Studies so far did not demonstrate that third-generation assays have a better performance for ioPTH in patients with PHPT. But a more rapid rate of PTH drop was observed in the third-generation assays. In surgery performed in patients with SHPT, it takes time for PTH concentrations to drop below the 50% cutoff after removal of the last hyperplastic gland using second-generation assays. More studies are needed to determine if third-generation assays offer a superior clinical utility for ioPTH monitoring, especially in patients with SHPT [50].
In addition, PTH measurement is used 20 min after thyroidectomy to determine if intensive calcium monitoring is needed (when the PTH level is >15 pg/mL using iPTH assays) and 4 hours after to predict postoperative hypocalcemia [51, 52]. There is no published study comparing the performance of different-generation PTH assays for this particular purpose, although one can argue that third-generation PTH measurement may better reflect the biological activity of parathyroid glands.
4. Toward standardization of PTH assays
There is a desperate need to reduce the significant inter-assay variability of PTH measurement that confounds the test interpretation and may affect clinical decision-making and cause patient harm. Assay standardization is therefore urgently required to improve the long-standing troubling situation in clinical PTH testing. Hormonal immunoassay standardization is inherently challenging because of the low circulating concentration, protein instability, and the differences in antibody-antigen complex formations; the presence of various PTH fragments and their different distributions in response to calcium, 25(OH) D status, and other effectors present additional hurdles to overcome.
International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), equipped with the experience for standardizing thyroid hormone and other protein assays, is undertaking the challenge to improve the PTH measurement in clinical communities. The IFCC Committee on Bone Metabolism has laid out the roadmap in a position statement where they set three major priorities:
Calibrate all current commercial PTH assays against a recognized International Standard, proposed to be the recombinant human PTH 1-84 standard (NIBSC 95/646) prepared by World Health Organization.
Facilitate the development of reference measurement procedure (RMP) for PTH (1-84) to enable the true metrological assignment of reference value for PTH primary, secondary and working standards in a network of reference laboratories.
Design studies to establish common reference intervals for PTH assays [30].
4.1 Assessing assay commutability and establishing reference PTH sample panels
The first task for the IFCC Working Group is to assess the commutability of PTH in a defined matrix, which is to demonstrate experimentally that the standard material and fresh patient specimens exhibit the same analytical response (regression line slope close to 1.0) when measured by two different methods.
A collaborative effort is currently undertaken to develop a protocol for the formal assessment of commutability. Once the commutability of the standard material is determined and deemed acceptable, it will be possible to use RMP to determine the recovery of PTH (1-84) in the appropriate matrices and then certify the values for secondary reference materials and external controls. Once such standards are available, assay manufacturers should use them to calibrate their assays.
In the meantime, the work is also underway to acquire an appropriate panel of plasma and/or serum samples for establishing PTH reference intervals. All the pre-analytical and physiological factors that can contribute to intra- and inter-individual variations as well as to increase inter-assay variability, as discussed in the previous section of this chapter, are to be carefully considered and minimized or ruled out.
One obvious challenge for this endeavor is the lack of consensus on how to define vitamin D sufficiency, insufficiency, and optimal vitamin D levels. The most often used definition of vitamin D sufficiency is the 25[OH]D concentration above which PTH cannot be suppressed further, however, this threshold varies with diseases states and is subject to analytical variability of 25-(OH) D assays [39]. Recently, a cross-sectional analysis of 14,289 CKD patients (stages 1−5) and a randomized control trial involving 429 patients with stage 3-4 CKD, showed levels of iPTH was not suppressed until serum 25(OH) D reached 40−50 ng/ml range, therefore, the target 25-(OH) D concentration may need to be raised in CKD patients [53, 54].
4.2 Developing candidate reference PTH measurement procedures for assay standardization
The liquid chromatography-tandem mass spectrometric (LC-MS/MS) method utilizes chromatographical separation and distinct mass/charge ratio of the product ion pairs to provide rigorous physicochemical characterization of target molecules in the biological mixture and therefore is ideal for developing reference measurement procedures for PTH. The technical advances in mass spectrometric analysis in the last decade enable LC-MS/MS to quantify PTH with accuracy and precision comparable to the results obtained with immunoassays in complex matrices, while it is more robust and flexible for identifying and measuring new or modified PTH fragments (i.e., oxidized PTH). Several published LC-MS/MS methods for PTH measurement already exist and can be readily refined and modified to become candidates for RMPs [5, 55].
IFCC working group has conducted a feasibility study as the first step to assess the suitability of a selected LC-MS/MS method as RMP for PTH quantification. In this study, 48 freeze-dried proficiency testing specimens with assigned values sent from UK NEQAS were reconstituted and analyzed by a published LC-MS/MS method used at the Mayo Clinic [56]. Results obtained from LC-MS/MS analysis were in excellent agreement with the target all laboratory trimmed mean used in the UK NEQAS for PTH and thus the feasibility of using the LC-MS/MS method as a candidate reference measurement procedure.
However, the analytical sensitivity of current MS methods still could not match that provided by immunoassays for PTH quantitation; moreover, current methods require proteolytic digestion of PTH before MS analysis, which is time-consuming and can introduce significant procedural variability. Some of the MS methods also include an immunoabsorbent step to select and enrich PTH. The specificity of the antibody used will influence what types of PTH fragments later be analyzed by LC-MS/MS and thus introduce biases to the final results. Therefore, there remain many hurdles to overcome in developing an MS-based RMP for PTH measurement [30].
Moreover, the employment of state-of-art liquid chromatography-high resolution mass spectrometry (LC-HRMS) could potentially profile various PTH fragments in different stages of CKD with a sensitivity comparable to that by immunoassays and thus offer a powerful tool to correlate PTH qualitative and quantitative changes with the progression of CKD [57].
5. Conclusions
Accurate quantitation of circulating PTH is challenging due to the presence of various molecular forms of PTH and its complex physiological interactions with other hormones and its effectors—calcium, and phosphate. PTH assays have been continuously evolving and improving since their debut six decades ago; the effort will continue to refine and adapt to resolve the issues at hand and meet the evolving clinical needs.
To improve the reliability of the PTH testing for diagnosis and monitoring along the pathway of patient management, IFCC has spearheaded an ambitious plan to standardize commercial PTH assays. It will require the collaborative efforts of academics, scientific and clinical communities, assay manufacturers, and the support of other stakeholders to achieve the goals. We can be optimistically hopeful that the communicable PTH reference material, the panels of qualified samples for establishing reference ranges, and the LC-MS/MS-based RMP method(s) will be available in the foreseeable future. Together they will enable calibration of all PTH assays with a single reliable international standard and allow accuracy-based external quality assessment. The better analytical tool can also empower us to gain more insight into the dynamic changes of PTH so we can optimize the testing to be used in the management of CKD to benefit patient care.
\n',keywords:"parathyroid hormone, intraoperative PTH assay, secondary hyperparathyroidism, chronic kidney diseases",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/81247.pdf",chapterXML:"https://mts.intechopen.com/source/xml/81247.xml",downloadPdfUrl:"/chapter/pdf-download/81247",previewPdfUrl:"/chapter/pdf-preview/81247",totalDownloads:3,totalViews:0,totalCrossrefCites:0,dateSubmitted:"December 9th 2021",dateReviewed:"February 23rd 2022",datePrePublished:"June 17th 2022",datePublished:null,dateFinished:"April 13th 2022",readingETA:"0",abstract:"In this chapter, we will start with a review of the methodological evolution of the clinical parathyroid hormone (PTH) assays, follow with a detailed discussion of clinical utility, analytical and clinical performances of the current second and third generation assays, their drawbacks and the efforts taken collaboratively by academia and industry to harmonize the PTH assays. Next, we will focus on the profiling of various forms of circulating PTH in healthy and diseases by LC-MS/MS-based analysis, which greatly contribute to the advancement of our understanding in the structure/function and pathophysiology of PTH over the past three decades. Finally, we will comment on the remaining challenges of the present PTH assays for patient management and point to the future research and development needs to meet the unmet medical needs in managing patients with hyperparathyroidism and chronic kidney diseases–mineral and bone disorder (CKD-MBD).",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/81247",risUrl:"/chapter/ris/81247",signatures:"Li-Sheng Chen",book:{id:"11262",type:"book",title:"Parathyroid Glands",subtitle:null,fullTitle:"Parathyroid Glands",slug:null,publishedDate:null,bookSignature:"Ph.D. Beyza Goncu",coverURL:"https://cdn.intechopen.com/books/images_new/11262.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80355-472-3",printIsbn:"978-1-80355-471-6",pdfIsbn:"978-1-80355-473-0",isAvailableForWebshopOrdering:!0,editors:[{id:"316670",title:"Ph.D.",name:"Beyza",middleName:null,surname:"Goncu",slug:"beyza-goncu",fullName:"Beyza Goncu"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Evolution of PTH assays",level:"1"},{id:"sec_3",title:"3. Unresolved problems with PTH assays",level:"1"},{id:"sec_3_2",title:"3.1 Inter-assay variability",level:"2"},{id:"sec_4_2",title:"3.2 Aggravating heterogeneity of circulating PTH in the disease states",level:"2"},{id:"sec_5_2",title:"3.3 Issues of concern related to testing procedures",level:"2"},{id:"sec_5_3",title:"3.3.1 Pre-analytical phase: Sample stability, sample type, and sampling time",level:"3"},{id:"sec_6_3",title:"3.3.2 Analytical phase: heterophilic antibodies interference",level:"3"},{id:"sec_7_3",title:"3.3.3 Post-analytical phase: reference ranges",level:"3"},{id:"sec_9_2",title:"3.4 Inability to discern oxidized from non-oxidized PTH by current clinical PTH assays",level:"2"},{id:"sec_10_2",title:"3.5 Clinical implications of the problematic PTH measurements",level:"2"},{id:"sec_10_3",title:"3.5.1 Clinical practice guidelines for PTH measurement in CKD-MBD",level:"3"},{id:"sec_11_3",title:"3.5.2 PTH assay incompatibility and the diagnosis of PHPT",level:"3"},{id:"sec_12_3",title:"3.5.3 Assay-dependent rate change in intra-operative PTH testing",level:"3"},{id:"sec_15",title:"4. Toward standardization of PTH assays",level:"1"},{id:"sec_15_2",title:"4.1 Assessing assay commutability and establishing reference PTH sample panels",level:"2"},{id:"sec_16_2",title:"4.2 Developing candidate reference PTH measurement procedures for assay standardization",level:"2"},{id:"sec_18",title:"5. Conclusions",level:"1"}],chapterReferences:[{id:"B1",body:'Fraser WD. Bone and mineral metabolism. In: Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 6th ed. Vol. 64. St. Louis, Missouri: Elsevier; 2018. pp. 1422-1491'},{id:"B2",body:'Bergwitz C, Jüppner H. Regulation of phosphate homeostasis by PTH, vitamin D, and FGF23. Annual Review of Medicine. 2010;61:91-104'},{id:"B3",body:'Peacock M. Phosphate metabolism in health and disease. Calcified Tissue International. 2021;108(1):3-15'},{id:"B4",body:'Habener JF, Segre GV, Powell D, Murray TM, Potts JT. Immunoreactive parathyroid hormone in circulation of man. 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K/DOQI-recommended intact PTH levels do not prevent low-turnover bone disease in hemodialysis patients. Kidney International. 2008;73(6):771-777'},{id:"B43",body:'Almond A, Ellis AR, Walker SW. Current parathyroid hormone immunoassays do not adequately meet the needs of patients with chronic kidney disease. Annals of Clinical Biochemistry. 2012;49(1):63-67'},{id:"B44",body:'KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD). Kidney International. Supplement. 2017;7(1):1-59'},{id:"B45",body:'Yalla N, Bobba G, Guo G, Stankiewicz A, Ostlund R. Parathyroid hormone reference ranges in healthy individuals classified by vitamin D status. Journal of Endocrinological Investigation. 2019;42(11):1353-1360'},{id:"B46",body:'Souberbielle JC, Massart C, Brailly-Tabard S, Cormier C, Cavalier E, Delanaye P, et al. Serum PTH reference values established by an automated third-generation assay in Vitamin D-replete subjects with normal renal function: Consequences of diagnosing primary hyperparathyroidism and the classification of dialysis patients. European Journal of Endocrinology. 2016;174(3):315-323'},{id:"B47",body:'Eastell R, Brandi ML, Costa AG, D’Amour P, Shoback DM, Thakker RV. Diagnosis of asymptomatic primary hyperparathyroidism: Proceedings of the fourth international workshop. The Journal of Clinical Endocrinology and Metabolism. 2014;99(10):3570-3579'},{id:"B48",body:'Fillée C, Keller T, Mourad M, Brinkmann T, Ketelslegers JM. Impact of vitamin D-related serum PTH reference values on the diagnosis of mild primary hyperparathyroidism, using bivariate calcium/PTH reference regions. Clinical Endocrinology. 2012;76(6):785-789'},{id:"B49",body:'Zhu CY, Sturgeon C, Yeh MW. Diagnosis and management of primary hyperparathyroidism. JAMA: The Journal of the American Medical Association. 2020;323(12):1186-1187'},{id:"B50",body:'Smit MA, Van Kinschot CMJ, Van Der Linden J, Van Noord C, Kos S. Clinical guidelines and PTH measurement: Does assay generation matter? Endocrine Reviews. 2019;40(6):1468-1480'},{id:"B51",body:'Orloff LA, Wiseman SM, Bernet VJ, Fahey TJ, Shaha AR, Shindo ML, et al. American thyroid association statement on postoperative hypoparathyroidism: Diagnosis, prevention, and management in adults. Thyroid. 2018;28(7):830-841'},{id:"B52",body:'Mazotas IG, Wang TS. The role and timing of parathyroid hormone determination after total thyroidectomy. Gland Surgery. 2017;6(Suppl. 1):S38-S48'},{id:"B53",body:'Ennis JL, Worcester EM, Coe FL, Sprague SM. Current recommended 25-hydroxyvitamin D targets for chronic kidney disease management may be too low. Journal of Nephrology. 2016;29(1):63-70'},{id:"B54",body:'Strugnell SA, Sprague SM, Ashfaq A, Petkovich M, Bishop CW. Rationale for raising current clinical practice guideline target for serum 25-hydroxyvitamin D in chronic kidney disease. American Journal of Nephrology. 2019;49(4):284-293'},{id:"B55",body:'Couchman L, Taylor DR, Krastins B, Lopez MF, Moniz CF. LC-MS candidate reference methods for the harmonisation of parathyroid hormone (PTH) measurement: A review of recent developments and future considerations. Clinical Chemistry and Laboratory Medicine. 2014;52:1251-1263'},{id:"B56",body:'Kumar V, Barnidge DR, Chen LS, Twentyman JM, Cradic KW, Grebe SK, et al. Quantification of serum 1-84 parathyroid hormone in patients with hyperparathyroidism by immunocapture in situ digestion liquid chromatography-tandem mass spectrometry. Clinical Chemistry. 2010;56(2):306-313'},{id:"B57",body:'Kritmetapak K, Losbanos LA, Hines JM, O’Grady KL, Ulmer CZ, Vesper HW, et al. Chemical characterization and quantification of circulating intact PTH and PTH fragments by high-resolution mass spectrometry in chronic renal failure. Clinical Chemistry. 2021;67(6):843-853'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Li-Sheng Chen",address:"lishengchen66@gmail.com",affiliation:'
Independent Researcher, Silver Spring, Maryland, USA
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Pressure ulcers (bedsores) were selected as the application area for SmartWoundCare due to their pervasiveness in healthcare and their associated impacts on patients’ quality of life and mortality, and electronic documentation is considered as an important intervention in pressure ulcer prevention and treatment. The chapter reviews the design of SmartWoundCare on Android and iOS platforms. Its benefits over paper‐based charting include automatically generated wound histories in graph and text formats, alerts and notifications for user‐set conditions, wound image galleries, and positioning for telehealth consultation by transmitting wound data across sites. The mobile app was implemented in a user trial in a long‐term care facility in Winnipeg, Canada, and the user trial illuminated that a key benefit of SmartWoundCare was the ability to take wound photographs. This feature had benefits for patients as well as caregivers. Consequently, algorithms were developed to analyse wound images for size and colour to provide additional indicators of wound progression.",signatures:"Marcia R. 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The Open Access model is applied to all of our publications and is designed to eliminate subscriptions and pay-per-view fees. This approach ensures free, immediate access to full text versions of your research.
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Open Access Funding
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For Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
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Added Value of Publishing with IntechOpen
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Indexing and listing across major repositories, see details ...
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Long-term archiving
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Visibility on the world's strongest OA platform
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Live Performance Metrics to track readership and the impact of your chapter
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Dissemination and Promotion
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Benefits of Publishing with IntechOpen
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Proven world leader in Open Access book publishing with over 10 years experience
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Most competitive prices in the market
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Optimized processes that assure your research is made available to the scientific community without delay
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Personal support during every step of the publication process
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+184,650 citations in Web of Science databases
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Currently strongest OA platform with over 175 million downloads
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This has compromised the ability of the environment to foster life and render its intrinsic values. Heavy metals are known to be naturally occurring compounds, but anthropogenic activities introduce them in large quantities in different environmental compartments. This leads to the environment’s ability to foster life being reduced as human, animal, and plant health become threatened. This occurs due to bioaccumulation in the food chains as a result of the nondegradable state of the heavy metals. Remediation of heavy metals requires special attention to protect soil quality, air quality, water quality, human health, animal health, and all spheres as a collection. Developed physical and chemical heavy metal remediation technologies are demanding costs which are not feasible, time-consuming, and release additional waste to the environment. This chapter summarises the problems related to heavy metal pollution and various remediation technologies. A case study in South Africa mines were also used.",book:{id:"6534",slug:"heavy-metals",title:"Heavy Metals",fullTitle:"Heavy Metals"},signatures:"Vhahangwele Masindi and Khathutshelo L. 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Dariva and Alexandre F. Galio",authors:[{id:"169261",title:"Dr.",name:"Camila",middleName:"G.",surname:"Dariva",slug:"camila-dariva",fullName:"Camila Dariva"},{id:"170138",title:"Dr.",name:"Alexandre",middleName:"Ferreira",surname:"Galio",slug:"alexandre-galio",fullName:"Alexandre Galio"}]}],mostDownloadedChaptersLast30Days:[{id:"76780",title:"Basics of Clay Minerals and Their Characteristic Properties",slug:"basics-of-clay-minerals-and-their-characteristic-properties",totalDownloads:1930,totalCrossrefCites:16,totalDimensionsCites:25,abstract:"Clay minerals such as kaolinite, smectite, chlorite, micas are main components of raw materials of clay and formed in presence of water. A large number of clays used to form the different structure which completely depends on their mining source. They are known as hydrous phyllosilicate having silica, alumina and water with variable amount of inorganic ions like Mg2+, Na+, Ca2+ which are found either in interlayer space or on the planetary surface. Clay minerals are described by presence of two-dimensional sheets, tetrahedral (SiO4) and octahedral (Al2O3). There are different clay minerals which are categorized based on presence of tetrahedral and octahedral layer in their structure like kaolinite (1:1 of tetrahedral and octahedral layers), smectite group of clay minerals (2:1 of tetrahedral and octahedral layers) and chlorite (2:1:1 of tetrahedral, octahedral and octahedral layers). The particle size of clay minerals is <2microns which can be present in form of plastic in presence of water and solidified when dried. The small size and their distinctive crystal structure make clay minerals very special with their unique properties including high cation exchange capacity, swelling behavior, specific surface area, adsorption capacity, etc. which are described in this chapter. Due to all these unique properties, clay minerals are gaining interest in different fields.",book:{id:"10949",slug:"clay-and-clay-minerals",title:"Clay and Clay Minerals",fullTitle:"Clay and Clay Minerals"},signatures:"Neeraj Kumari and Chandra Mohan",authors:[{id:"258132",title:"Dr.",name:"Chandra",middleName:null,surname:"Mohan",slug:"chandra-mohan",fullName:"Chandra Mohan"},{id:"352399",title:"Dr.",name:"Neeraj",middleName:null,surname:"Kumari",slug:"neeraj-kumari",fullName:"Neeraj Kumari"}]},{id:"51535",title:"An Introduction to Hydrogels and Some Recent Applications",slug:"an-introduction-to-hydrogels-and-some-recent-applications",totalDownloads:11734,totalCrossrefCites:70,totalDimensionsCites:140,abstract:"Hydrogels have existed for more than half a century, and today they have many applications in various processes ranging from industrial to biological. There are numerous original papers, reviews, and monographs focused on the synthesis, properties, and applications of hydrogels. This chapter covers the fundamental aspects and several applications of hydrogels based on the old and the most recent publications in this field.",book:{id:"5251",slug:"emerging-concepts-in-analysis-and-applications-of-hydrogels",title:"Emerging Concepts in Analysis and Applications of Hydrogels",fullTitle:"Emerging Concepts in Analysis and Applications of Hydrogels"},signatures:"Morteza Bahram, Naimeh Mohseni and Mehdi Moghtader",authors:[{id:"179718",title:"Prof.",name:"Morteza",middleName:null,surname:"Bahram",slug:"morteza-bahram",fullName:"Morteza Bahram"},{id:"185713",title:"Dr.",name:"Naimeh",middleName:null,surname:"Mohseni",slug:"naimeh-mohseni",fullName:"Naimeh Mohseni"},{id:"185714",title:"Dr.",name:"Mehdi",middleName:null,surname:"Moghtader",slug:"mehdi-moghtader",fullName:"Mehdi Moghtader"}]},{id:"70661",title:"Bioremediation Techniques for Polluted Environment: Concept, Advantages, Limitations, and Prospects",slug:"bioremediation-techniques-for-polluted-environment-concept-advantages-limitations-and-prospects",totalDownloads:2672,totalCrossrefCites:10,totalDimensionsCites:27,abstract:"Environmental pollution has been rising in the past few decades due to increased anthropogenic activities. Bioremediation is an attractive and successful cleaning technique to remove toxic waste from polluted environment. Bioremediation is highly involved in degradation, eradication, immobilization, or detoxification diverse chemical wastes and physical hazardous materials from the surrounding through the all-inclusive and action of microorganisms. The main principle is degrading and converting pollutants to less toxic forms. Bioremediation can be carried out ex-situ and in-situ, depending on several factors, which include but not limited to cost, site characteristics, type, and concentration of pollutants. Hence, appropriate bioremediation technique is selected. Additionally, the major methodologies to develop bioremediation are biostimulation, bioaugmentation, bioventing, biopiles, and bioattenuation provided the environmental factors that decide the completion of bioremediation. Bioremediation is the most effective, economical, eco-friendly management tool to manage the polluted environment. All bioremediation techniques have its own advantage and disadvantage because it has its own specific applications.",book:{id:"9343",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",title:"Trace Metals in the Environment",fullTitle:"Trace Metals in the Environment - New Approaches and Recent Advances"},signatures:"Indu Sharma",authors:[{id:"301262",title:"Associate Prof.",name:"Indu",middleName:null,surname:"Sharma",slug:"indu-sharma",fullName:"Indu Sharma"}]},{id:"18275",title:"Modeling and Identification of Parameters the Piezoelectric Transducers in Ultrasonic Systems",slug:"modeling-and-identification-of-parameters-the-piezoelectric-transducers-in-ultrasonic-systems",totalDownloads:10197,totalCrossrefCites:3,totalDimensionsCites:5,abstract:null,book:{id:"201",slug:"advances-in-ceramics-electric-and-magnetic-ceramics-bioceramics-ceramics-and-environment",title:"Advances in Ceramics",fullTitle:"Advances in Ceramics - Electric and Magnetic Ceramics, Bioceramics, Ceramics and Environment"},signatures:"Pawel Fabijanski and Ryszard Lagoda",authors:[{id:"13086",title:"Dr.",name:"Pawel",middleName:null,surname:"Fabijański",slug:"pawel-fabijanski",fullName:"Pawel Fabijański"}]},{id:"60680",title:"Environmental Contamination by Heavy Metals",slug:"environmental-contamination-by-heavy-metals",totalDownloads:16251,totalCrossrefCites:187,totalDimensionsCites:407,abstract:"The environment and its compartments have been severely polluted by heavy metals. This has compromised the ability of the environment to foster life and render its intrinsic values. Heavy metals are known to be naturally occurring compounds, but anthropogenic activities introduce them in large quantities in different environmental compartments. This leads to the environment’s ability to foster life being reduced as human, animal, and plant health become threatened. This occurs due to bioaccumulation in the food chains as a result of the nondegradable state of the heavy metals. Remediation of heavy metals requires special attention to protect soil quality, air quality, water quality, human health, animal health, and all spheres as a collection. Developed physical and chemical heavy metal remediation technologies are demanding costs which are not feasible, time-consuming, and release additional waste to the environment. This chapter summarises the problems related to heavy metal pollution and various remediation technologies. A case study in South Africa mines were also used.",book:{id:"6534",slug:"heavy-metals",title:"Heavy Metals",fullTitle:"Heavy Metals"},signatures:"Vhahangwele Masindi and Khathutshelo L. Muedi",authors:[{id:"225304",title:"Dr.",name:"Vhahangwele",middleName:null,surname:"Masindi",slug:"vhahangwele-masindi",fullName:"Vhahangwele Masindi"},{id:"241403",title:"M.Sc.",name:"Khathutshelo",middleName:"Lilith",surname:"Muedi",slug:"khathutshelo-muedi",fullName:"Khathutshelo Muedi"}]}],onlineFirstChaptersFilter:{topicId:"14",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82948",title:"Study on Miniaturization of Antenna Using Metamaterials",slug:"study-on-miniaturization-of-antenna-using-metamaterials",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.106222",abstract:"Metamaterials (MTMs) are artificially built materials intended to give its properties from the internal structure, rather than the chemical composition found in natural materials. Electric permittivity (ε) and magnetic permeability (μ) are the two basic parameters which describe the electromagnetic property of a material or medium. Permittivity describes how a material is affected when it is placed in electric field. And permeability describes how a material is affected in presence of magnetic field. Metamaterials may have either negative permittivity or permeability or both may be negative simultaneously. The concept of metamaterials has additionally been utilized to design different kinds of patches with upgraded performance, such as improved gain and enhanced efficiency. Also, it has been utilized for the scaling down of patches. Two parameters are utilized in the collected works for antennas using metamaterials. We can adjust the refractive index of the metamaterial to positive, near-zero or negative values. Utilization of epsilon negative, MNG (μ - Mu negative) or DNG (double negative) are called metamaterial- based antennas and the use of metamaterial unit cell for example complementary split ring resonator, split ring resonator and so on are alluded as metamaterial inspired antennas. The design of complementary split ring resonator and its equivalent circuit will be discussed in this work. CSRR (complementary split ring resonator) provides both isolation enhancement and miniaturization for MIMO antenna.",book:{id:"11824",title:"Metamaterials - History, Current State, Applications, and Perspectives",coverURL:"https://cdn.intechopen.com/books/images_new/11824.jpg"},signatures:"Andrews Christina Josephine Malathi"},{id:"83080",title:"Boron Doping in Next-Generation Materials for Semiconductor Device",slug:"boron-doping-in-next-generation-materials-for-semiconductor-device",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.106450",abstract:"The article surveys the most recent achievements starting with the boron doping mechanism, mainly focused on doping in semiconductor materials such as Si, Ge, graphene, carbon nanotube, or other 2D materials. Frequently used doping methodologies are discussed, including ion implantation and solid-phase doping, mainly focused on recent developing techniques of monolayer doping. These doped materials’ structural, electronic, and chemical properties are addressed to understand the boron doping effect better. Theoretical and experimental information and data are used to support such atomic-level effects. Therefore, this review can provide valuable suggestions and guidelines for materials’ properties manipulation by boron doping for further research exploration.",book:{id:"11762",title:"Characteristics and Applications of Boron",coverURL:"https://cdn.intechopen.com/books/images_new/11762.jpg"},signatures:"Linh Chi T. Cao, Luqman Hakim and Shu-Han Hsu"},{id:"83055",title:"Boron Clusters in Biomedical Applications: A Theoretical Viewpoint",slug:"boron-clusters-in-biomedical-applications-a-theoretical-viewpoint",totalDownloads:6,totalDimensionsCites:0,doi:"10.5772/intechopen.106215",abstract:"In this chapter, we presented an analysis of the recent advances in the applications of boron clusters in biomedical fields such as the development of biosensors and drug delivery systems on the basis of quantum chemical calculations. Biosensors play an essential role in many sectors, e.g., law enforcement agencies for sensing illicit drugs, medical communities for detecting overdosed medications from human and animal bodies, etc. The drug delivery systems have theoretically been proposed for many years and subsequently implemented by experiments to deliver the drug to the targeted sites by reducing the harmful side effects significantly. Boron clusters form a rich and colorful family of atomic clusters due to their unconventional structures and bonding phenomena. Boron clusters and their complexes have various biological activities such as the drug delivery, imaging for diagnosis, treatment of cancer, and probe of protein-biomolecular interactions. For all of these reactivities, the interaction mechanisms and the corresponding energetics between biomaterials and boron clusters are of essential importance as a basic step in the understanding, and thereby design of relevant materials. During the past few years, attempts have been made to probe the nature of these interactions using quantum chemical calculations mainly with density functional theory (DFT) methods. This chapter provides a summary of the theoretical viewpoint on this issue.",book:{id:"11762",title:"Characteristics and Applications of Boron",coverURL:"https://cdn.intechopen.com/books/images_new/11762.jpg"},signatures:"Ehsan Shakerzadeh, Elham Tahmasebi, Long Van Duong and Minh Tho Nguyen"},{id:"83048",title:"Structural, Magnetic, and Magnetodielectric Properties of Bi-Based Modified Ceramic Composites",slug:"structural-magnetic-and-magnetodielectric-properties-of-bi-based-modified-ceramic-composites",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.106569",abstract:"In this chapter, we introduce a promising composite material, which can be used as a potential candidate in the field of charge storage, sensors, and spintronic devices. The structural, magnetic, and magnetodielectric properties of the pure cum composite samples are investigated. The Rietveld refinement of the X-ray data confirmed the presence of a single (A21am) and mixed phases (A21am + R-3c + Pbam) in the pure and composite sample, correspondingly. The SEM microstructure suggests the contrasting nature of the homogeneous and heterogeneous distribution of grains in the corresponding pure and composite sample. The magnetic properties of the composite sample increase due to the enhanced exchange interaction between the different magnetic ions. The frequency-dependent dielectric subjected to a constant magnetic field indicates the signature of magnetodielectric (MD) coupling for both the samples. The field variation of the MD loop shows the symmetric hysteresis loop in the composite due to the addition of magnetostrictive La0.67Sr0.33MnO3 and the non-collinear antiferromagnetic Bi2Fe4O9 phase. The maximum value of MD% (~0.12%) is enhanced by ~13 times in the composite than in the pure sample. Therefore, the improved MD coupling and symmetric switching of the MD loop of the composite make it a suitable candidate for low power consumption storage devices.",book:{id:"11117",title:"Smart and Advanced Ceramics and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11117.jpg"},signatures:"Rasmita Jena, Kouru Chandrakanta and Anil Kumar Singh"},{id:"83035",title:"Breaking the Property Trade-Offs by Using Entropic Conceptions",slug:"breaking-the-property-trade-offs-by-using-entropic-conceptions",totalDownloads:11,totalDimensionsCites:0,doi:"10.5772/intechopen.106532",abstract:"Entropic conception has been used as an effective strategy for developing materials to break the property recordings of current materials, for example, breaking the trade-off between the high-strength and low-ductility structural alloys. The performance of materials usually under a complex circumstance, a balance of multiple properties, for example, combined the high-strength, high ductility, high conductivity, high corrosion resistance, high irradiation resistance, etc., the strategy of high-entropy-alloy (HEA) will provide a materials design and development technology to realize the goal. Magnetic materials usually exhibit excellent magnetic properties but weak mechanical properties and corrosion resistance. The reported unique behaviors of HEAs, for example, self-healing effects may be the mechanism for the high irradiation resistance of the HEAs, and self-sharpening behaviors of the tungsten-based HEAs main closely be related to the serration behaviors.",book:{id:"11468",title:"High Entropy Materials - Microstructures and Properties",coverURL:"https://cdn.intechopen.com/books/images_new/11468.jpg"},signatures:"Yong Zhang and Xuehui Yan"},{id:"82929",title:"Prediction of Solubility and Miscibility Parameters of Bismuth-Arsenic Complex and Amorphous Mineral Compounds Using Molecular Dynamics Simulation",slug:"prediction-of-solubility-and-miscibility-parameters-of-bismuth-arsenic-complex-and-amorphous-mineral",totalDownloads:4,totalDimensionsCites:0,doi:"10.5772/intechopen.106316",abstract:"Bismuth is one of the most difficult impurities to remove in mining concentrates and low concentrations generate problems in silver and copper refineries. Therefore, financial penalties are established when concentrations exceed 0.05%. Some researchers had used arsenic to remove bismuth with results of up to 52% of extraction. Unfortunately, this mechanism is not yet fully understood. The objective of this research was to obtain the solubility parameters of amorphous mineral compounds, including bismuth-based compounds, through computational simulation using molecular dynamics. The composition of the mineral sample was determined by X-ray diffraction and the crystalline species were obtained and modeled using Materials Studio software. The nanostructures were optimized by an energy minimization methodology using the Broyden-Fletcher-Goldfarb-Shanno algorithm and were validated using the figure of merit equation and density. Simulations were performed using the Universal Force Field at constant pressure and temperature. The results of the minerals identified in the sample were compared with arsenic trioxide, indicating miscibility between As2O3 and Bi2O3, possible miscibility with 10 other minerals, and immiscibility with the rest. The results indicate that As2O3 can be successfully used for the removal of Bi2O3 without a negative effect on the recovery of other minerals of higher commercial value.",book:{id:"11467",title:"Bismuth-Based Nanostructured Materials",coverURL:"https://cdn.intechopen.com/books/images_new/11467.jpg"},signatures:"Francisco Adrián De la Torre-Martínez, Efren Delgado, María Dolores Josefina Rodríguez Rosales, Hiram Medrano-Roldán, Javier López-Miranda and Damián Reyes-Jáquez"}],onlineFirstChaptersTotal:82},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:11,numberOfPublishedChapters:91,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:332,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:11,numberOfPublishedChapters:142,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:124,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:12,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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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"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:2,paginationItems:[{id:"89",title:"Education",coverUrl:"https://cdn.intechopen.com/series_topics/covers/89.jpg",isOpenForSubmission:!1,editor:{id:"260066",title:"Associate Prof.",name:"Michail",middleName:null,surname:"Kalogiannakis",slug:"michail-kalogiannakis",fullName:"Michail Kalogiannakis",profilePictureURL:"https://mts.intechopen.com/storage/users/260066/images/system/260066.jpg",biography:"Michail Kalogiannakis is an Associate Professor of the Department of Preschool Education, University of Crete, and an Associate Tutor at School of Humanities at the Hellenic Open University. He graduated from the Physics Department of the University of Crete and continued his post-graduate studies at the University Paris 7-Denis Diderot (D.E.A. in Didactic of Physics), University Paris 5-René Descartes-Sorbonne (D.E.A. in Science Education) and received his Ph.D. degree at the University Paris 5-René Descartes-Sorbonne (PhD in Science Education). His research interests include science education in early childhood, science teaching and learning, e-learning, the use of ICT in science education, games simulations, and mobile learning. He has published over 120 articles in international conferences and journals and has served on the program committees of numerous international conferences.",institutionString:"University of Crete",institution:{name:"University of Crete",institutionURL:null,country:{name:"Greece"}}},editorTwo:{id:"422488",title:"Dr.",name:"Maria",middleName:null,surname:"Ampartzaki",slug:"maria-ampartzaki",fullName:"Maria Ampartzaki",profilePictureURL:"https://mts.intechopen.com/storage/users/422488/images/system/422488.jpg",biography:"Dr Maria Ampartzaki is an Assistant Professor in Early Childhood Education in the Department of Preschool Education at the University of Crete. Her research interests include ICT in education, science education in the early years, inquiry-based and art-based learning, teachers’ professional development, action research, and the Pedagogy of Multiliteracies, among others. She has run and participated in several funded and non-funded projects on the teaching of Science, Social Sciences, and ICT in education. She also has the experience of participating in five Erasmus+ projects.",institutionString:"University of Crete",institution:{name:"University of Crete",institutionURL:null,country:{name:"Greece"}}},editorThree:null},{id:"90",title:"Human Development",coverUrl:"https://cdn.intechopen.com/series_topics/covers/90.jpg",isOpenForSubmission:!0,editor:{id:"191040",title:"Dr.",name:"Tal",middleName:null,surname:"Dotan Ben-Soussan",slug:"tal-dotan-ben-soussan",fullName:"Tal Dotan Ben-Soussan",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBf1QAG/Profile_Picture_2022-03-18T07:56:11.jpg",biography:"Tal Dotan Ben-Soussan, Ph.D., is the director of the Research Institute for Neuroscience, Education and Didactics (RINED) – Paoletti Foundation. Ben-Soussan leads international studies on training and neuroplasticity from neurophysiological and psychobiological perspectives. As a neuroscientist and bio-psychologist, she has published numerous articles on neuroplasticity, movement and meditation. She acts as an editor and reviewer in several renowned journals and coordinates international conferences integrating theoretical, methodological and practical approaches on various topics, such as silence, logics and neuro-education. She lives in Assisi, Italy.",institutionString:"Research Institute for Neuroscience, Education and Didactics, Patrizio Paoletti Foundation",institution:null},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:12,paginationItems:[{id:"83113",title:"Agoraphobic Dispositions towards Action Research: Teacher Education Students’ Perceptions and Experiences",doi:"10.5772/intechopen.106188",signatures:"Davison Zireva",slug:"agoraphobic-dispositions-towards-action-research-teacher-education-students-perceptions-and-experien",totalDownloads:1,totalCrossrefCites:null,totalDimensionsCites:0,authors:[{name:"Davison",surname:"Zireva"}],book:{title:"Active Learning - Research and Practice for STEAM and social sciences education",coverURL:"https://cdn.intechopen.com/books/images_new/11481.jpg",subseries:{id:"89",title:"Education"}}},{id:"83053",title:"Apologies in L2 French in Canadian Context",doi:"10.5772/intechopen.106557",signatures:"Bernard Mulo Farenkia",slug:"apologies-in-l2-french-in-canadian-context",totalDownloads:0,totalCrossrefCites:0,totalDimensionsCites:0,authors:[{name:"Bernard",surname:"Mulo Farenkia"}],book:{title:"Second Language Acquisition - Learning Theories and Recent Approaches",coverURL:"https://cdn.intechopen.com/books/images_new/11480.jpg",subseries:{id:"89",title:"Education"}}},{id:"82903",title:"Walking Accessibility to Primary Healthcare Services: An Inequity Factor for Olders in the Lisbon Metropolitan Area (Portugal)",doi:"10.5772/intechopen.106265",signatures:"Eduarda Marques da Costa, Ana Louro, Nuno Marques da Costa, Mariana Dias and Marcela Barata",slug:"walking-accessibility-to-primary-healthcare-services-an-inequity-factor-for-olders-in-the-lisbon-met",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Social Aspects of Ageing - Selected Challenges, Analyses, and Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11479.jpg",subseries:{id:"90",title:"Human Development"}}},{id:"82622",title:"Contemporary Geographical Gerontology: Reconciling Space and Place in Population Ageing",doi:"10.5772/intechopen.105863",signatures:"Hamish Robertson",slug:"contemporary-geographical-gerontology-reconciling-space-and-place-in-population-ageing",totalDownloads:13,totalCrossrefCites:0,totalDimensionsCites:0,authors:[{name:"Hamish",surname:"Robertson"}],book:{title:"Social Aspects of Ageing - Selected Challenges, Analyses, and Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11479.jpg",subseries:{id:"90",title:"Human Development"}}}]},overviewPagePublishedBooks:{paginationCount:0,paginationItems:[]},openForSubmissionBooks:{paginationCount:1,paginationItems:[{id:"11568",title:"Staphylococcal Infections - Recent Advances and Perspectives",coverURL:"https://cdn.intechopen.com/books/images_new/11568.jpg",hash:"92c881664d1921c7f2d0fee34b78cd08",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"July 8th 2022",isOpenForSubmission:!0,editors:[{id:"59719",title:"Dr.",name:"Jaime",surname:"Bustos-Martínez",slug:"jaime-bustos-martinez",fullName:"Jaime Bustos-Martínez"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},onlineFirstChapters:{paginationCount:21,paginationItems:[{id:"83000",title:"Purine and Pyrimidine Pathways as Antimalarial Targets",doi:"10.5772/intechopen.106468",signatures:"Yacoba V.T. Minnow and Vern L. 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He previously worked as a post-doctoral fellow at the Ben-Gurion University of Negev, Israel; University of the Free State, South Africa; and Central University of Technology Bloemfontein, South Africa. He obtained his Ph.D. in Organic Chemistry from Nagaoka University of Technology, Japan. He has published more than seventy-four journal articles and attended several national and international conferences as speaker and chair. Dr. Kendrekar has received many international awards. He has several funded projects, namely, anti-malaria drug development, MRSA, and SARS-CoV-2 activity of curcumin and its formulations. He has filed four patents in collaboration with the University of Central Lancashire and Mayo Clinic Infectious Diseases. His present research includes organic synthesis, drug discovery and development, biochemistry, nanoscience, and nanotechnology.",institutionString:"Visiting Scientist at Lipid Nanostructures Laboratory, Centre for Smart Materials, School of Natural Sciences, University of Central Lancashire",institution:null},{id:"428125",title:"Dr.",name:"Vinayak",middleName:null,surname:"Adimule",slug:"vinayak-adimule",fullName:"Vinayak Adimule",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428125/images/system/428125.jpg",biography:"Dr. Vinayak Adimule, MSc, Ph.D., is a professor and dean of R&D, Angadi Institute of Technology and Management, India. He has 15 years of research experience as a senior research scientist and associate research scientist in R&D organizations. He has published more than fifty research articles as well as several book chapters. He has two Indian patents and two international patents to his credit. Dr. Adimule has attended, chaired, and presented papers at national and international conferences. He is a guest editor for Topics in Catalysis and other journals. He is also an editorial board member, life member, and associate member for many international societies and research institutions. His research interests include nanoelectronics, material chemistry, artificial intelligence, sensors and actuators, bio-nanomaterials, and medicinal chemistry.",institutionString:"Angadi Institute of Technology and Management",institution:null},{id:"284317",title:"Prof.",name:"Kantharaju",middleName:null,surname:"Kamanna",slug:"kantharaju-kamanna",fullName:"Kantharaju Kamanna",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284317/images/21050_n.jpg",biography:"Prof. K. Kantharaju has received Bachelor of science (PCM), master of science (Organic Chemistry) and Doctor of Philosophy in Chemistry from Bangalore University. He worked as a Executive Research & Development @ Cadila Pharmaceuticals Ltd, Ahmedabad. He received DBT-postdoc fellow @ Molecular Biophysics Unit, Indian Institute of Science, Bangalore under the supervision of Prof. P. Balaram, later he moved to NIH-postdoc researcher at Drexel University College of Medicine, Philadelphia, USA, after his return from postdoc joined NITK-Surthakal as a Adhoc faculty at department of chemistry. Since from August 2013 working as a Associate Professor, and in 2016 promoted to Profeesor in the School of Basic Sciences: Department of Chemistry and having 20 years of teaching and research experiences.",institutionString:null,institution:{name:"Rani Channamma University, Belagavi",country:{name:"India"}}},{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"436430",title:"Associate Prof.",name:"Mesut",middleName:null,surname:"Işık",slug:"mesut-isik",fullName:"Mesut Işık",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/436430/images/19686_n.jpg",biography:null,institutionString:null,institution:{name:"Bilecik University",country:{name:"Turkey"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a scientist and Principal Investigator at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering the lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via artificial intelligence-based analyses of exosomal Raman signatures. Dr. Paul also works on spatial multiplex immunofluorescence-based tissue mapping to understand the immune repertoire in lung cancer. Dr. Paul has published in more than sixty-five peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award and the 2022 AAISCR-R Vijayalaxmi Award for Innovative Cancer Research. He is a senior member of the Institute of Electrical and Electronics Engineers (IEEE) and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/system/329795.png",biography:"Dr. Mohd Aftab Siddiqui is an assistant professor in the Faculty of Pharmacy, Integral University, Lucknow, India, where he obtained a Ph.D. in Pharmacology in 2020. He also obtained a BPharm and MPharm from the same university in 2013 and 2015, respectively. His area of research is the pharmacological screening of herbal drugs/natural products in liver cancer and cardiac diseases. He is a member of many professional bodies and has guided many MPharm and PharmD research projects. Dr. Siddiqui has many national and international publications and one German patent to his credit.",institutionString:"Integral University",institution:null}]}},subseries:{item:{id:"38",type:"subseries",title:"Pollution",keywords:"Human Activity, Pollutants, Reduced Risks, Population Growth, Waste Disposal, Remediation, Clean Environment",scope:"
\r\n\tPollution is caused by a wide variety of human activities and occurs in diverse forms, for example biological, chemical, et cetera. In recent years, significant efforts have been made to ensure that the environment is clean, that rigorous rules are implemented, and old laws are updated to reduce the risks towards humans and ecosystems. However, rapid industrialization and the need for more cultivable sources or habitable lands, for an increasing population, as well as fewer alternatives for waste disposal, make the pollution control tasks more challenging. Therefore, this topic will focus on assessing and managing environmental pollution. It will cover various subjects, including risk assessment due to the pollution of ecosystems, transport and fate of pollutants, restoration or remediation of polluted matrices, and efforts towards sustainable solutions to minimize environmental pollution.
",coverUrl:"https://cdn.intechopen.com/series_topics/covers/38.jpg",hasOnlineFirst:!1,hasPublishedBooks:!0,annualVolume:11966,editor:{id:"110740",title:"Dr.",name:"Ismail M.M.",middleName:null,surname:"Rahman",slug:"ismail-m.m.-rahman",fullName:"Ismail M.M. Rahman",profilePictureURL:"https://mts.intechopen.com/storage/users/110740/images/2319_n.jpg",biography:"Ismail Md. Mofizur Rahman (Ismail M. M. Rahman) assumed his current responsibilities as an Associate Professor at the Institute of Environmental Radioactivity, Fukushima University, Japan, in Oct 2015. He also has an honorary appointment to serve as a Collaborative Professor at Kanazawa University, Japan, from Mar 2015 to the present. \nFormerly, Dr. Rahman was a faculty member of the University of Chittagong, Bangladesh, affiliated with the Department of Chemistry (Oct 2002 to Mar 2012) and the Department of Applied Chemistry and Chemical Engineering (Mar 2012 to Sep 2015). Dr. Rahman was also adjunctly attached with Kanazawa University, Japan (Visiting Research Professor, Dec 2014 to Mar 2015; JSPS Postdoctoral Research Fellow, Apr 2012 to Mar 2014), and Tokyo Institute of Technology, Japan (TokyoTech-UNESCO Research Fellow, Oct 2004–Sep 2005). \nHe received his Ph.D. degree in Environmental Analytical Chemistry from Kanazawa University, Japan (2011). He also achieved a Diploma in Environment from the Tokyo Institute of Technology, Japan (2005). Besides, he has an M.Sc. degree in Applied Chemistry and a B.Sc. degree in Chemistry, all from the University of Chittagong, Bangladesh. \nDr. Rahman’s research interest includes the study of the fate and behavior of environmental pollutants in the biosphere; design of low energy and low burden environmental improvement (remediation) technology; implementation of sustainable waste management practices for treatment, handling, reuse, and ultimate residual disposition of solid wastes; nature and type of interactions in organic liquid mixtures for process engineering design applications.",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"201020",title:"Dr.",name:"Zinnat Ara",middleName:null,surname:"Begum",slug:"zinnat-ara-begum",fullName:"Zinnat Ara Begum",profilePictureURL:"https://mts.intechopen.com/storage/users/201020/images/system/201020.jpeg",biography:"Zinnat A. Begum received her Ph.D. in Environmental Analytical Chemistry from Kanazawa University in 2012. She achieved her Master of Science (M.Sc.) degree with a major in Applied Chemistry and a Bachelor of Science (B.Sc.) in Chemistry, all from the University of Chittagong, Bangladesh. Her work affiliations include Fukushima University, Japan (Visiting Research Fellow, Institute of Environmental Radioactivity: Mar 2016 to present), Southern University Bangladesh (Assistant Professor, Department of Civil Engineering: Jan 2015 to present), and Kanazawa University, Japan (Postdoctoral Fellow, Institute of Science and Engineering: Oct 2012 to Mar 2014; Research fellow, Venture Business Laboratory, Advanced Science and Social Co-Creation Promotion Organization: Apr 2018 to Mar 2021). 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\r\n\tThe era of antibiotics led us to the illusion that the problem of bacterial infection is over. However, bacterial flexibility and adaptation mechanisms allow them to survive and grow in extreme conditions. The best example is the formation of a sophisticated society of bacteria defined as a biofilm. Understanding the mechanism of bacterial biofilm formation has changed our perception of the development of bacterial infection but successfully eradicating biofilm remains a challenge. Considering the above, it is not surprising that bacteria remain a major public health threat despite the development of many groups of antibiotics. Additionally, increasing prevalence of acquired antibiotic resistance forces us to realize that we are far from controlling the development of bacterial infections. On the other hand, many infections are endogenous and result from an unbalanced relationship between the host and the microorganism. The increasing use of immunosuppressants, such as chemotherapy or organ transplantation, increases the incidence of patients highly susceptible to bacterial infections in the population.
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