Performance parameters of typical solar collector fields [8, 9, 10, 11, 12, 13, 14, 15, 16, 17].
\r\n\t
",isbn:"978-1-83881-111-2",printIsbn:"978-1-83880-992-8",pdfIsbn:"978-1-83881-112-9",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"acb2875b3bfc189c9881a9b44b6a5184",bookSignature:"Dr. Abdo Abou Jaoudé",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11865.jpg",keywords:"Linear Operators, Normal Operators, Spectral Theorem, Applications, Differential Operators, Integral Operators, Functional Calculus, Complex Variables, Complex Analysis, Theory, Recent Advances, Latest Trends",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 13th 2022",dateEndSecondStepPublish:"June 21st 2022",dateEndThirdStepPublish:"August 20th 2022",dateEndFourthStepPublish:"November 8th 2022",dateEndFifthStepPublish:"January 7th 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"6 days",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Abdo Abou Jaoudé is a pioneering Associate Professor of Mathematics and Statistics at Notre Dame University-Louaizé. He holds two PhDs in Mathematics and Prognostics from the Lebanese University and Aix-Marseille University. His research interests are in the field of mathematics.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"248271",title:"Dr.",name:"Abdo",middleName:null,surname:"Abou Jaoudé",slug:"abdo-abou-jaoude",fullName:"Abdo Abou Jaoudé",profilePictureURL:"https://mts.intechopen.com/storage/users/248271/images/system/248271.jpg",biography:"Abdo Abou Jaoudé has been teaching for many years and has a passion for researching and teaching mathematics. He is currently an Associate Professor of Mathematics and Statistics at Notre Dame University-Louaizé (NDU), Lebanon. He holds a BSc and an MSc in Computer Science from NDU, and three PhDs in Applied Mathematics, Computer Science, and Applied Statistics and Probability, all from Bircham International University through a distance learning program. He also holds two PhDs in Mathematics and Prognostics from the Lebanese University, Lebanon, and Aix-Marseille University, France. Dr. Abou Jaoudé's broad research interests are in the field of applied mathematics. He has published twenty-three international journal articles and six contributions to conference proceedings, in addition to seven books on prognostics, pure and applied mathematics, and computer science.",institutionString:"Notre Dame University - Louaize",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Notre Dame University – Louaize",institutionURL:null,country:{name:"Lebanon"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"15",title:"Mathematics",slug:"mathematics"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"252211",firstName:"Sara",lastName:"Debeuc",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/252211/images/7239_n.png",email:"sara.d@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2270",title:"Fourier Transform",subtitle:"Materials Analysis",isOpenForSubmission:!1,hash:"5e094b066da527193e878e160b4772af",slug:"fourier-transform-materials-analysis",bookSignature:"Salih Mohammed Salih",coverURL:"https://cdn.intechopen.com/books/images_new/2270.jpg",editedByType:"Edited by",editors:[{id:"111691",title:"Dr.Ing.",name:"Salih",surname:"Salih",slug:"salih-salih",fullName:"Salih Salih"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"872",title:"Organic Pollutants Ten Years After the Stockholm Convention",subtitle:"Environmental and Analytical Update",isOpenForSubmission:!1,hash:"f01dc7077e1d23f3d8f5454985cafa0a",slug:"organic-pollutants-ten-years-after-the-stockholm-convention-environmental-and-analytical-update",bookSignature:"Tomasz Puzyn and Aleksandra Mostrag-Szlichtyng",coverURL:"https://cdn.intechopen.com/books/images_new/872.jpg",editedByType:"Edited by",editors:[{id:"84887",title:"Dr.",name:"Tomasz",surname:"Puzyn",slug:"tomasz-puzyn",fullName:"Tomasz Puzyn"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"70699",title:"Solar Thermochemical Fuel Generation",doi:"10.5772/intechopen.90767",slug:"solar-thermochemical-fuel-generation",body:'\nDue to population growth and rapid industrial development, world energy demand has increased significantly. Compared with the previous generation, the world’s population has increased rapidly by 2 billion [1], and this mainly comes from the population growth of developing countries, and rapid population growth poses more severe challenges to increasingly scarce energy and resource supplies. The importance of energy for social development is self-evident. In order to ensure the supply of energy, a large amount of fossil energy is used, which at the same time has a serious impact on the environment, leading to increasingly serious problems of atmospheric pollution and the greenhouse effect. Therefore, improving energy efficiency and using more clean energy and exploring a sustainable development path compatible with energy use and the environment have become one of the important topics in energy science research.
\nThe efficient use of renewable energy is of great significance. Among the many renewable energy sources, solar energy has become one of the best choices for future energy sources with its unique advantages, which is the most abundant renewable energy source and widely distributed.
\nSolar energy is a huge amount of clean energy. It is of great significance to develop and utilize solar energy reasonably and efficiently. However, the efficient use of solar energy also faces limitations, such as the low energy density of solar energy, the unstable energy supply, the discontinuous time and spatial distribution of solar radiation, and the difficulty of direct storage [2, 3]. Therefore, solar energy is converted into chemical energy stored in fuels, which is generally considered to be an effective solution to make up for solar defects [2, 3, 4, 5, 6].
\nThere are mainly four approaches for converting solar energy into chemical energy to generate solar fuel, which is illustrated in Figure 1. The photobiological process is limited by the low energy conversion efficiency now, and it is still at a very early stage of the development [7]. The other three methods have their own properties and have attracted lots of attention. Photo-electrolysis approach is most convenient, but it is also limited by the conversion rate, and researchers are seeking for the catalysts which have better performance. The electrolysis using photovoltaic (PV) materials and electrolyzer is the most mature approach for producing solar fuel. However, the PV materials can only utilize the light with a certain range of wavelength (usually short wavelength light), and the other part of sunlight absorbed is converted into thermal energy, which is wasted as residual heat, leading to a limited PV cell efficiency (the commercial PV cell efficiency is about 15%; the highest multiple-junction PV cell efficiency in lab is higher than 40% with high cost). The total energy efficiency from solar energy to chemical energy is the product of solar power efficiency (e.g., PV cell efficiency) and electrolysis efficiency, so the total efficiency has potential to be further improved. Compared with electrolysis, solar fuel generation by thermochemistry can utilize the sunlight with whole solar spectrum, which has a high theoretical energy efficiency. So the solar thermochemical fuel generation is a promising method and will be discussed in this chapter in details.
\nIllustration of solar fuel via various approaches.
Figure 2 is a schematic diagram of the solar thermochemical energy conversion process. Solar energy with lower energy density is received by solar collectors and converted into solar thermal energy. Solar thermal energy enters the absorber through heat transfer and drives the chemical reaction, so that low-energy-density solar energy is stored in the form of solar fuel as chemical energy with high energy density, which is relatively easy for storage and transportation. The sustainable and stable use of solar energy is achieved by transporting solar fuel to remote and needed places for power generation and chemical processes, etc., and solving the discontinuity of solar distributed in time and space by means of chemical energy storage.
\nIllustration of solar thermochemical energy conversion process.
There are many researches about the reaction and system for solar thermochemical fuel generation published, and some of the significant parts have been classified in Figure 3. The two main fuels from solar energy are hydrogen and carbon monoxide, which both have great higher heating values and are potential to be utilized in the future, especially hydrogen, as hydrogen has the following characteristics:
Rich hydrogen energy reserves. On the earth, hydrogen mainly exists in the form of hydrocarbons and water, and more than 70% of the earth’s surface is covered by water. Therefore, the earth contains a huge amount of hydrogen and has great potential for development.
The energy density of hydrogen is large. The higher heating value of hydrogen is much higher than that of hydrocarbons and alcohol compounds, and the consumption of hydrogen energy is increasing every year.
Hydrogen is renewable. Hydrogen can be obtained from water, and the oxidation of hydrogen produces water. Therefore, the hydrogen combustion and energy release cycle does not consume other substances.
Hydrogen energy is clean energy. Whether hydrogen is consumed by direct combustion or fuel cell power generation, the only product is water, without any waste pollution, which is clean and environmentally friendly.
Hydrogen is relatively easy to be converted and stored. Compared with other energy sources such as solar energy, wind energy, electrical energy, and thermal energy, hydrogen is a chemical raw material and is easily to be converted into hydrocarbons for storage, thereby expanding the scope of hydrogen energy in time and space.
Classification of solar thermochemical fuel generation.
Different chemical reaction processes require different temperatures, so it is necessary to match the solar thermal energy temperature with the chemical reaction temperature for efficient energy utilization. Different solar thermal temperatures need to be achieved with different forms of solar collectors for matching various chemical reactions.
\nThe heat collection temperature of solar collectors depends on many factors, but the most important factor is the concentration ratio, which is the ratio of the total area of the opening of the collector mirror field to the spot area on the focal plane. Concentration ratio is an important parameter for designing concentrating solar thermal utilization. Under the same conditions, the higher the concentration ratio, the higher the heat collection temperature. In a unit of time, the energy emitted by a black body per unit area is proportional to the fourth power of its temperature, and solar energy is close to a 6000 K black body, so the radiant energy it emits is:
\nAmong them,
Illustration of solar radiation trajectory.
After the absorber absorbs energy, the temperature will rise. Assuming the temperature rises to
According to the second law of thermodynamics, heat can only be transferred spontaneously from a high-temperature object to a low-temperature object, so the temperature
According to the definition of the concentration ratio, it is:
\nAmong them,
In the actual application process, there are two types of common solar concentrating forms: linear focusing and point focusing. Among them, linear focusing solar collectors include parabolic trough solar collectors and linear Fresnel solar collectors. Because the collectors have different heat collection methods, they also have different light collection ratios and heat collection temperatures. Because point-focused solar collector focuses in two dimensions and line-focused solar collector focuses in one-dimensional directions, point-focused solar collectors usually have a larger concentration ratio, which could approach a greater temperature. However, high temperature usually means higher requirements for materials and processing industries, higher radiation losses, and heat costs of the collector. Table 1 lists the typical solar thermal power generation mirror field parameters. In thermal power plants, a higher temperature for power generation will allow the Rankine cycle to have a higher Carnot efficiency, leading to a greater power generation efficiency.
\nType | \nAnnual power generation efficiency (%) | \nPeak efficiency (%) | \nOperating temperature (°C) | \nConcentration ratio | \n
---|---|---|---|---|
Parabolic trough collector power plant | \n14 | \n25 | \n400 | \n30–100 | \n
Linear Fresnel collector power plant | \n13 | \n18 | \n300–400 | \n30 | \n
Disc collector power plant | \n20 | \n32 | \n550–750 | \n1000–10,000 | \n
Tower collector power plant | \n16 | \n22 | \n400–600 | \n500–5000 | \n
In the process of collecting solar energy by using a solar collector, energy is dissipated due to radiation. The absorption efficiency is defined as the ratio of the solar energy absorbed by the absorption cavity to the total solar energy projected by the collector into the absorption cavity, given as [18]:
\n\n\n
where
The relationship among the ideal absorption efficiency of the collector, the concentration ratio, and the heat collection temperature.
With multiplying the obtained absorption efficiency by the Carnot cycle efficiency, the system efficiency can be obtained, which is the maximum theoretical conversion efficiency from the solar thermal energy obtained to work or electricity [18]:
\nwhere
The relationship among the maximum efficiency from solar thermal energy to work, the concentration ratio, and the heat collection temperature.
When decomposing water to produce hydrogen without relying on fossil energy, the temperature required for thermochemical reactions is about 1300–1800°C. According to Figures 5 and 6, it can be seen that a tower or dish collector with a concentration ratio of 5000 should be selected. When using fossil fuel (e.g., methane) to split water for hydrogen generation, the reaction temperature could be decreased to 700–1000°C. A tower or dish solar concentrator with a concentration ratio of 1000 should be used. The reaction temperature of the novel solar hydrogen permeation membrane alternating cycle methane reforming system introduced later in this chapter is about 350–400°C, and a trough solar concentrator with a concentration ratio of 80–100 is enough for it, which has a much lower cost compared with tower or the dish-type solar concentrating collector.
\nAccording to Eq. (8), when the concentration ratio
By maintaining Eq. (9) equal to 0, the optimal heat collection temperature can be obtained at a given concentration ratio, and the optimal heat collection temperature can be substituted into Eq. (8) to obtain the sun at the best heat collection temperature. The maximum theoretical efficiency from solar energy to work is shown in Figure 7.
\nVariation of maximum theoretical efficiency from solar energy to work and optimal thermal energy collection temperature with concentration ratio.
From Figure 7, as the concentration ratio increases, the intensity of radiation received per unit area of the collector increases, so both the optimal heat collection temperature and the maximum theoretical efficiency increase. Because the solar collector has a fixed concentration ratio in practical applications, Figure 7 has guiding significance for determining the optimal heat-collecting temperature for a solar heat collector with a specific concentration ratio. The solar thermal energy of the system has the maximum work efficiency at the best concentration ratio.
\nThe existing thermochemical cycle for hydrogen production mainly includes metal oxide system thermochemical cycle, sulfur-containing system, sulfuric acid decomposition method, metal-halide system, and reformed methane hydrogen production. All of the thermochemical cycles could be classified as multi-step thermochemical cycles and two-step thermochemical cycles.
\nThere are four main types of hydrogen production in sulfur-containing systems: iodine-sulfur cycle, H2SO4-H2S cycle, sulfuric acid-methanol cycle, and sulfate cycle. Among them, the iodine-sulfur cycle is the most famous. It was invented by the United States GA company in the 1970s, so it is also called the GA cycle. The process is shown in Figure 8. The main reaction process is as follows:
\nIllustration of iodine-sulfur cycle.
\n
GA company found [19] that the excess I2 exists, and HI and H2SO4 can be separated into two liquid phases, which is the basis for the development of the IS cycle. The advantages of the IS cycle are using of thermal energy below 1000°C for hydrogen generation, closed circuit, only water being needed to be added in the circulation process, and the expected efficiency which can reach 52%. The disadvantages are concentrated sulfuric acid being highly corrosive when heated at high temperature; the equilibrium decomposition ratio of HI being low (20%); and the reaction intermediate products sulfur dioxide and iodine being easy to cause pollution and liable to have side reactions.
\nThis type of method is best known as the Westinghouse cycle [20], and its main process is shown in Figure 9. The highest temperature in the process needs to be above 800°C, and the efficiency of the cycle can reach 40%. If multi-stage electrolysis is used, it can reach 46%. However, the disadvantage is that concentrated sulfuric acid is highly corrosive at high temperatures and has high requirements for material selection.
\nWestinghouse cycle diagram.
The most famous in this system is the UT-3 cycle proposed by the University of Tokyo. The main process is as follows:
\nSakurai [21] found that the hydrolysis of calcium bromide was the slowest during this cycle, because the calcium oxide agglomerated, reducing the reaction interface area. The addition of lauric acid as a foaming agent for dispersing the calcium oxide aggregates can improve the performance of the reaction. The Argonne National Laboratory in the United States has also researched and developed this process [22]. Its main feature is the decomposition or formation of HBr by electrolytic method or “cold” plasma method. This reaction has the following advantages: its expected thermal efficiency is 35–40%, and if the power is generated at the same time, the overall efficiency can be improved by 10%; the two-step key reaction is a gas-solid reaction, which significantly simplifies the separation of products and reactants; the elements used are cheap and readily available; the process involves only solid and gaseous reactants and products. However, the separation of intermediate products in the reaction process is also a problem and challenge in the process.
\nThe common two-step thermochemical cycle hydrogen production process is mainly metal oxide thermochemical cycle, which has the following three forms:
\nOxide:
\nor
\nHydride:
\nHydroxide:
\nAmong them, metal oxide thermochemical hydrogen production is the most common. The process is shown in Figure 10.
\nMetal oxide thermochemical cycle for hydrogen production.
As shown in Figure 10, metal oxides are reduced by releasing oxygen at high temperatures, and oxidized with water at low temperatures, taking away oxygen atoms from water molecules to generate hydrogen. During the thermochemical cycle, metal oxides can be reduced to simple metals, such as:
\nMetal oxides may also be reduced from higher valence to lower valence oxides, such as:
\nAmong them, metal Zn is easy to form a dense oxide film, which is wrapped on the metal surface to prevent the reaction from proceeding. Wegner et al. [23] designed a spray reactor for solving this problem. By increasing the specific surface area of metal Zn to increase the contact area in the reaction, the experiment proves that the chemical conversion of Zn can reach 83%. The disadvantage of this method is that the metal Zn needs to be gasified and atomized, which requires large energy consumption; Zn, Sn, and other metals are also easily oxidized again during the decomposition process, affecting the reaction efficiency. The oxidation rate of iron oxide is easily reduced due to sintering, and ferrite has strong reducing ability. It can reduce CO2 to C solid element and cover the surface of ferrite to prevent the reaction from proceeding. One of the materials currently considered to be the most suitable for the thermochemical cycle of metal oxides is cerium oxide (CeO2), because cerium oxide can efficiently reduce water or carbon dioxide to hydrogen or carbon monoxide [24], and cerium oxide also has good anti-coking properties. The specific reaction equations are:
\nHigh temperature (reduction step):
\nLow temperature (oxidation step):
\nIn the two-step thermochemical cycle hydrogen production process, because there is a large heat transfer temperature difference between the “oxidation step” and “reduction step” (e.g., the temperature difference between cerium oxide heat transfer is about 700°C), the thermal energy recovery of solid materials has always been a very difficult problem. Hao et al. [25] proposed an “isothermal” thermochemical cycle, that is, the “oxidation step” and “reduction step” reactions are performed at the same temperature. The “isothermal” thermochemical cycle effectively overcomes the defect that a large amount of solid sensible heat in the “dual-temperature” thermochemical cycle cannot be efficiently recovered and does not generate thermal stress, which can maintain high energy utilization efficiency at high temperatures. However, the isothermal thermochemical cycle also has certain limitations that need to be resolved, such as the requirement of maintaining a quite low oxygen partial pressure, less hydrogen production in a single cycle, etc. The thermochemical cycle with metal oxide can also be utilized for CO generation from CO2, and the thermodynamics is similar to that of H2 generation from H2O, which will not be discussed here.
\nNowadays, more than 95% of the hydrogen for refinery use is produced via hydrocarbon steam reforming [26]. Industrial hydrogen production through methane steam reforming exceeds 50 million tons annually and accounts for 2–5% of global energy consumption [27]. Methane steam reforming process for hydrogen production is usually described by the following reactions:
\nwhere the reversible water-gas shift reaction Eq. (11) is sometimes considered as superimposed onto the methane reforming reaction Eq. (10) for conveniences of analysis on methane conversion:
\nThe methane dry reforming is the reaction between methane and carbon dioxide for syngas generation, given as:
\nThe reforming reactions, Eqs. (10), (12), and (13), are highly endothermic, and a large amount of heat is often provided by burning a supplemental amount of methane [28], which will decrease the heat value of fuel gas generated by 22% for the same amount of methane consumed and release large amounts of greenhouse gas CO2 [29]. In recent years, as the technologies of concentrated solar energy (CSE) and solar thermal utilization improve rapidly, methane reforming driven by CSE emerged as a promising method for hydrogen production [30], which derives heat from solar energy instead of fossil fuels. Besides, solar thermal energy with relatively low temperatures (compared with methane combustion) is absorbed by methane reforming reaction and upgraded to the chemical energy with higher energy level (ratio of exergy change \n
In order to achieve the high-efficient progress of the solar methane reforming reaction, research on solar methane reforming reactors has also continued. Klein et al. [33] proposed a schematic diagram of a fluidized bed reactor. This experiment is a methane dry reforming experiment, where gas reactants and carbon particles are mixed and passed into the reactor together. The reactor can achieve a concentration ratio of 3000 through primary and secondary light concentration, and the reaction temperature is between 950 and 1450°C with the ratio of carbon dioxide to methane changes from 1: 1 to 6: 1, which has a maximum methane conversion of 90%. Edwards et al. [34] studied methane steam reforming in a solar tubular reactor, which is condensed by a 107 m2 dish condenser. The condensing temperature can reach 850°C, and the pressure can reach 20 bars. The reactor can stably produce hydrogen, but there is no detailed introduction on the conversion rate in the literature. The device for hydrogen production by metal oxide thermochemical cycling was proposed by Steinfeld et al. [35]. The system contains a 51.8 m2 heliostat to focus the sunlight at first, and then the sunlight passed through a parabolic surface with an opening area of 2.7 m2 to focus it again. The final focusing ratio was 3500. During the reaction, ZnO particles with an average particle diameter of 0.4 μm were sent into a cylindrical reaction chamber for reaction by methane. The products were Zn simple substance and synthesis gas (H2, CO). The reactor can reach 50% methane conversion at 1030°C.
\nMethane decomposition is also an endothermic reaction at 600–1200°C, given as:
\nSolar methane decomposition has been researched in both indirectly and directly heated reactors from solar thermal energy. A summary of experimental study has been listed in Table 2.
\nParticipant | \nQsolar (kW) | \nPressure (bar) | \nReactor type | \nReactant conversion (%) | \nEfficiency (%) | \nRef. | \n|
---|---|---|---|---|---|---|---|
PSI | \n5 | \n>1 | \n1600 | \nVortex flow | \n64 | \n15.1a, 16.2b | \n[37] | \n
PSI | \n5 | \n>1 | \n1600 | \nParticle flow | \n99 | \n16.1b | \n[38] | \n
PROMES-CNRS | \n10 | \n0.4 | \n1773 | \nTubular | \n98 | \n4.8b | \n[39, 40] | \n
PROMES-CNRS | \n50 | \n0.45 | \n1928 | \nTubular | \n100 | \n13.5a, 15.2b | \n[41] | \n
NREL | \n6 | \n1 | \n2133 | \nAerosol flow | \n90 | \n2b | \n[42] | \n
PROMES-CNRS | \n0.8 | \n0.61 | \n1700 | \nNozzle type | \n95 | \n5.9a | \n[43] | \n
Summary of experimental research on solar methane decomposition [36].
\n\n
\n\n
Methanol reforming and decomposition also attracts lots of attention in the field of solar thermochemical fuel generation [44], as the reaction temperature is about 150–300°C, which is quite low and easy to be maintained by line-focusing solar collector (parabolic trough collector or linear Fresnel lens) with low cost. The reaction equations of methanol reforming and decomposition are given as:
\nBoth of the two reactions are endothermic, which can convert the low-level solar thermal energy (low temperature) into high-level chemical energy, and have been researched with combining with other systems, like PV cell module, and combined cooling heating and power in downstream.
\nBiomass is widespread and is often perceived as a carbon-neutral source of energy. Solar biomass gasification is a clean route to obtain fuels, which may also reach liquid fuel for vehicle or jet utilization. Detailed reviews on solar biomass gasification have been conducted by Epstein et al. [45], Lédé [46], Nzihou et al. [47], and Puig-Arnavat et al. [48], which will not be discussed here. A summary of experimental work published in gasification of solid hydrocarbon feed has been listed in Table 3.
\nFeed | \nQsolar (kW) | \nGasifying agent | \nReactor type | \nReactant conversion (%) | \nProduct yield (%) | \nEfficiency (%) | \nRef. | \n|
---|---|---|---|---|---|---|---|---|
Bituminous coal | \n1.2 | \n1600 | \nCO2 | \nFluidized bed quartz tubular reactor | \n65 | \n— | \n8a | \n[49] | \n
Pet coke | \n5 | \n1818 | \nSteam | \nVortex flow | \n87 | \n35 (H2), 15 (CO) | \n9a, 20b | \n[50] | \n
Pet coke—water slurry | \n5 | \n1500 | \nSteam | \nVortex flow | \n87 | \n65 (H2), 25 (CO) | \n4.7a, 17.4b | \n[51] | \n
Petroleum VR | \n5 | \n1573 | \nSteam | \nVortex flow | \n50 | \n68 (H2), 15 (CO) | \n2c, 19a | \n[52] | \n
Coal coke | \n0.94 | \n1123 | \nCO2 | \nInternally circulating fluidized bed | \n— | \n— | \n12a | \n[53] | \n
IS, SS, STP, fluff, SAC, beech charcoal | \n5 | \n1490 | \nSteam | \nPacked bed | \n100 | \nH2/CO = 1.5, CO2/CO = 0.2 | \n29d, | \n[54] | \n
Beech charcoal | \n3 | \n1523 | \nSteam | \nParticle flow reactor | \n30 | \n— | \n1.53b | \n[55] | \n
Coal coke | \n1.1 | \n1573 | \nCO2 | \nFluidized bed | \n42 | \n— | \n14a | \n[56] | \n
Coal coke | \n3 | \n1773 | \nCO2 | \nInternally circulating fluidized bed | \n73 | \n— | \n12f | \n[57] | \n
LRK, tire chips, Fluff, DSS, IS, SB | \n150 | \n1350–1453 | \nSteam | \nPacked bed | \n36–100 | \nH2/CO = 2–5.2 | \n25-35d, | \n[58] | \n
Summary of experimental research published in gasification of solid hydrocarbon feed [36].
\n\n
\n\n
\n\n
\n\n
\n\n
\n\n
Solar thermochemistry usually requires high temperature (e.g., above 4000°C for H2O splitting; 3000°C for CO2 splitting; 700–1000°C for methane reforming), which requires high concentration ratio and large mirror area, and the system will be more complex and expensive. In situ separation by a permeable membrane for a target product shifts thermodynamic equilibrium of chemical reactions in favor of reactants conversion, which equivalently lowers solar collection temperature. Combination of membrane reactor and solar thermal collection offers unique advantages in many respects, such as the increment of conversion rate, decrease of reaction temperature, and emission reduction, which are otherwise unattainable by either alone. Besides, the all-solid-state feature and isothermal operation enable compact design of solar fuel reactors with minimized thermal stress. Now, the selective permeation membrane for gas species in high temperature is mainly oxygen permeation membrane, hydrogen permeation membrane, and carbon dioxide permeation membrane, which have been researched for solar thermochemical fuel generation.
\nPerovskites, ZrO2 and CeO2 (or doped ZrO2 and CeO2), usually constitute the selective oxygen permeation membrane utilized in high temperature (>600°C). Wang et al. [59] proposed a theoretical framework for the thermodynamic analysis of solar oxygen permeation membrane reactor, and the solar-to-fuel efficiency (ratio of the higher heating value of products to the total energy input) can reach as high as 89% in methane-assisted membrane reactor. Zhu et al. [60] brought up a thermodynamic model of ceria dense membrane for CO2 splitting, and the energy efficiency is above 10% at 1800 K without heat recovery. Steinfeld et al. [61, 62] have done a lot of experimental researches about solar CO2 splitting for CO generation by oxygen permeation membrane with 100% selectivity (e.g., La0.6Sr0.4Co0.2Fe0.8O3-δ at 1030°C [61], CeO2 at 1600°C [62]), and Ozin [63] said the research of Steinfeld is an elegant demonstration and an exciting breakthrough for continuous CO2 splitting in a single step, at a single temperature, in a single reactor.
\nThe materials of the hydrogen permeation membrane are various, such as metal (e.g., palladium, nickel), perovskites, pyrochlores, fluorites, polymers, which are usually used in the reaction of reforming, splitting, partial oxidation of hydrocarbon, splitting of other hydrogen carriers (e.g., NH3), and water-gas shift reaction. Li et al. [30] first presented an innovative solar-assisted hybrid power system integrated with methane steam reforming in membrane reactor, and the simulation results showed that capture ratio of CO2 is 91% and exergy efficiency and thermal efficiency are 58 and 51.6% (10.2 and 2.2% points higher than the CO2 capture from exhaust cycle), respectively. Said et al. [64] simulated a CFD model about solar molten salt-heated H2-selective membrane reformer for methane upgrading and hydrogen generation, and the results showed the fuel heating value upgrade of 40% with methane conversion rate of 99% and hydrogen recovery of 87% at 600°C. Wang et al. [65] put forward a novel reactor, which realized direct methane steam reforming in parabolic trough collector integrated with hydrogen permeation membrane reactor, and the system can perform high and stable efficiency (above 80%) at 400°C. Mallapragada et al. [66] proposed a novel system that consists of oxygen permeation membrane and hydrogen permeation membrane for solar water splitting, and the solar-to-H2 efficiency (ratio of the lower heating value of hydrogen to the reversible work input for Gibbs free energy change of water splitting) is 72.4–80.1% at the concentration ratios of 2000–10,000. Sui et al. [67] reported an exploration on an efficient solar thermochemical water-splitting system enhanced by hydrogen permeation membrane, which has showed a sharply enhanced conversion rate of 87.8% at 1500°C and 10−5 bar at permeated side (versus 1.26% with oxygen permeation membrane or isothermal thermochemical cycle). Recently, a promising method for hydrogen generation without carbon emitting by ammonia decomposition in a catalytic palladium membrane reactor for hydrogen separation driven by solar energy has been theoretically proposed, and the first-law thermodynamic efficiency, net solar-to-hydrogen efficiency, and exergy efficiency can reach as high as 86.86, 40.08, and 72.07%, respectively [68].
\nCarbon dioxide permeation membrane includes mixed e−/CO32− conducting membrane, O2−/CO32− conducting membrane, OH−/CO32− conducting membrane (hydroxide/ceramic dual-phase membrane), etc. [69, 70]. The combination between carbon dioxide permeation membrane and solar energy is very limited now. The combination of hydrogen permeation membrane and carbon dioxide permeation membrane has been proposed for methane steam reforming by way of an alternate H2 and CO2 separation driven by solar energy [71]. The carbon dioxide permeation membrane has great potential to be utilized for the hydrocarbon reforming or decomposition for CO2 separation and capture in the future.
\nThough the solar membrane reactor has lots of advantages and immense potential for application mentioned above, the efficient approach to lower the partial pressure of gas product (or avoid the relatively low pressure) is the main challenge to maintain a high energy conversion rate, and the improvement of stability and permeability of membrane material at corresponding reaction temperature is also significant. These issues have potential areas for big breakthroughs and require further studies to address. The multiple product separation with membrane reactor may be a promising method to increase the energy efficiency, due to a relatively high partial pressure and less separation energy required [71].
\nThis chapter has reviewed the state-of-the-art researches about solar thermochemical fuel generation, and the highlighted conclusions are listed:
The thermodynamics in solar thermochemical fuel generation has been analyzed, and the maximum theoretical efficiency from solar energy to work has been obtained.
The most representative solar thermochemical reactions (e.g., H2O/CO2 splitting, hydrocarbon reforming, and decomposition) have been reviewed, and the advantages and drawbacks have been analyzed and discussed.
Thermochemical cycle and membrane reactor driven by solar energy have been systematically introduced, which could decrease the reaction temperature and have the potential to be widely utilized in the future, especially the membrane reactor, which could purify the product with a continuous operation.
This work is funded by the National Natural Science Foundation of China (no. 51906179) and the State Scholarship Fund (No. 201906275035) from China Scholarship Council.
\nAntiphospholipid syndrome (APS) was first described in 1983 with steadily improving clinical and scientific refinements since that time. It was initially recognized with the discovery of lupus anticoagulant immunoglobulin that binds to phospholipids and proteins associated with the cell membrane and its association with other autoimmune conditions. Over the years, the clinical manifestations of APS were further delineated, followed by the discovery of other antiphospholipid antibodies. Currently, APS is defined as an autoimmune condition characterized by the presence of venous or arterial thrombosis and/or pregnancy-related complications in patients with antiphospholipid antibodies [1]. Notably, APS can occur as a
Clinically, APS can manifest in a variety of ways and affect multiple organ systems. Presenting symptoms can range from relatively benign to severe. One subtype (to be discussed in Section 2) termed catastrophic APS (CAPS) is defined as APS that affects >3 organs in a short period of time (<7 days) with pathologic evidence of small-vessel occlusion. The most common venous manifestation of APS is deep vein thrombosis, while stroke is the most common arterial manifestation of this disease [4]. Obstetric complications include placental insufficiency and recurrent pregnancy loss, typically after 10 weeks of gestation. There are, however, a multitude of other manifestations including cardiac valvular disease, coronary artery disease, livedo reticularis, renal small artery vasculopathy, and thrombocytopenia, which are
Antiphospholipid antibodies (aPL) are a serological marker for APS and their presence is key to the definition and classification for APS. Phospholipids are molecules found in the blood that aid in clot formation. They form complexes with other plasma proteins and are the target of aPL antibodies; thus, one may expect to clinically see a bleeding disorder when phospholipids are disrupted. However, these autoantibodies primarily cause endothelial dysfunction and disruption of coagulation factors as they compete with coagulation factors for available phospholipids, thereby leading to a procoagulant state and clot formation [6]. The pathophysiology of aPL antibodies is not fully elucidated, but the current thought is that of a “two-hit” hypothesis. The first hit being a patient-specific susceptibility, and the second hit being a trigger or inciting event. This theory is based on the idea that about 1–5% of the population may have positive aPL antibodies without any clinical manifestations, indicating the need for a trigger that leads to the pathologic state [2, 4]. In a patient carrying aPL antibodies, endothelial cell activation occurs in the setting of oxidative stress in conditions such as infection, surgery, and pregnancy. This is thought to subsequently lead to a series of events including complement activation, cytokine release, increased expression of tissue factor on endothelial cells, increased platelet adhesiveness, and impairment of thrombolysis [2, 4]. Overall, this creates a procoagulant state leading to the range of clinical manifestations as described.
aPL antibodies are a heterogeneous group of autoantibodies that primarily include
There are a variety of antiphospholipid antibodies associated with APS, as detected with different methods, some are overlapping, but each has distinct properties. Image adapted from Misita et al. [
The presence of LA alone is thought to hold the highest risk for thrombosis among all antiphospholipid antibodies. Thrombotic risk is much lower in patients who have only a positive aCL or anti-B2GPI antibody [1, 3]. The risk is thought to be much higher however in patients with multiple positive antibodies, especially those found to be “triple positive” [3]. Thrombotic risk is also much higher in patients who have secondary APS is associated with SLE and in patients with primary APS with concurrent vascular comorbidities including hypertension, hypercholesterolemia, tobacco, and oral contraceptive use [7].
The initial classification criteria for APS, called the Sapporo criteria, was first developed in 1999 and most recently updated in 2006 [1]. As shown in Table 1, the criteria currently require one clinical manifestation of thrombosis or pregnancy complication, and one laboratory criteria present on two occasions at least 12 weeks apart.
Antiphospholipid antibody syndrome (APS) is present if at least one of the clinical criteria and one of the laboratory criteria that follow arc met* clinical criteria |
1. Vascular thrombosis† One or more clinical episodes‡ of arterial, venous, or small vessel thrombosis§, in any tissue or organ. Thrombosis must be confirmed by objective validated criteria (i.e. unequivocal findings of appropriate imaging studies or histopathology). For histopathologic confirmation, thrombosis should be present without significant evidence of inflammation in the vessel wall. |
2. Pregnancy morbidity
|
Laboratory criteria** 1. Lupus anticoagulant (LA) present in plasma, on two or more occasions at least 12 weeks apart, detected according to the guidelines of the International Society on Thrombosis and Hemostasis (Scientific Subcommittee on LAs/phospholipid-dependent antibodies) [10, 11]. |
2. Anticardiolipin (aCL) antibody of IgG and/or IgM isotype in scrum or plasma, present in medium or high titer (i.e. >40 GPL or MPL, or >the 99th percentile), on two or more occasions, at least 12 weeks apart, measured by a standardized ELISA. |
3. Anti-β2 glycoprotein-I antibody of IgG and/or IgM isotype in scrum or plasma (in titer > the 99th percentile), present on two or more occasions, at least 12 weeks apart, measured by a standardized ELISA, according to recommended procedures. |
The classification criteria for APS [1].
Classification of APS should be avoided if less than 12 weeks or more than 5 years separate the positive aPL test and the clinical manifestation.
Coexisting inherited or acquired factors for thrombosis arc, not reasons for excluding patients from APS trials. However, two subgroups of APS patients should be recognized, according to (a) the presence, and (b) the absence of additional risk factors for thrombosis. Indicative (but not exhaustive) such eases include: age (>55 in men, and >65 in women), and the presence of any of the established risk factors for cardiovascular disease (hypertension, diabetes mellitus, elevated LDL or low HDL cholesterol, cigarette smoking, family history of premature cardiovascular disease, body mass index ≥30 kg m–2, microalbuminuria, estimated GFR < 60 ml min−1), inherited thrombophilias, oral contraceptives, nephrotic syndrome, malignancy, immobilization, and surgery. Thus, patients who fulfill criteria should be stratified according to contributing causes of thrombosis.
A thrombotic episode in the past could be considered as a clinical criterion, provided that thrombosis is proved by appropriate diagnostic means and that no alternative diagnosis or cause of thrombosis is found.
Superficial venous thrombosis is not included in the clinical criteria.
Generally accepted features of placental insufficiency include: (i) abnormal or non-reassuring fetal surveillance test(s), e.g. a non-reactive non-stress test, suggestive of fetal hypoxemia, (ii) abnormal Doppler flow velocimetry waveform analysis suggestive of fetal hypoxemia, e.g. absent end-diastolic flow in the umbilical artery, (iii) oligohydramnios, e.g. an amniotic fluid index of 5 cm or less, or (iv) a postnatal birth weight less than the 10th percentile for the gestational age.
Investigators arc strongly advised classifying APS patients in studies into one of the following categories: I, more than one laboratory criteria present (any combination): IIa, LA present alone; IIb, aCL antibody present alone; IIc, anti-β2 glycoprotein-I antibody present alone.
As mentioned, there are other autoantibodies implicated in APS that are not yet included in the classification criteria. The remainder of this chapter will discuss the clinical manifestations, epidemiology, pathophysiology, diagnosis, and treatment in more detail.
APS can present as a wide range of clinical manifestations with the major clinical features consisting of arterial and venous thromboses, and obstetrical complications. The most common obstetrical manifestations of APS are recurrent early miscarriage, placental insufficiency, early pre-eclampsia, and fetal death, all of which should prompt evaluation for the presence of aPL [12].
Thrombotic events in APS may occur in virtually any vascular bed, with the cerebral circulation being the arterial territory most commonly affected, usually in the form of stroke or transient ischemic attack [13]. APS has also been associated with many other clinical features including livedo reticularis, epilepsy, thrombocytopenia, and cognitive dysfunction, however, the strength of association is not sufficiently high to include them in the syndrome definition. The clinical characteristics of a cohort of 1000 patients with APS (Euro-Phospholipid Project) are displayed in Table 2 [14].
As described in Section 1, the first set of criteria for APS was established in Sapporo, Japan in 1999 after an expert workshop [9]. This was modified, including the addition of anti-β2GPI antibodies in Sydney, Australia in 2006. The revised APS classification criteria strongly recommend investigating coexisting inherited and acquired thrombosis risk factors in patients with APS [1]. A recent assessment of the 2006 revised APS classification criteria has shown that only 59% of the patients meeting the 1999 APS Sapporo classification criteria met the revised criteria [15]. In addition, many of the older studies evaluated for only a few of the specific aPL antibodies now thought to be important in stroke risk, accepted low positive titers and many looked at only one-time point, hence it is difficult to apply the results of those studies [16]. While the purpose of the criteria was to help choose patients for clinical trials, it is the best available tool to avoid over-diagnosis of APS in clinical practice [17].
CAPS is a rare and potentially fatal complication of APS. As described in Table 3, the clinical presentation is characterized by acute multi-organ failure due to thromboses of three or more organs within 1 week, associated with the presence of aPL and thrombocytopenia [16]. CAPS can be seen as the first presentation of APS or can be triggered by infection, surgery, or trauma in patients with known APS [19].
Manifestation | No. (%) of patients |
---|---|
Deep vein thrombosis | 389 (38.9%) |
Other peripheral thrombi | 248 (24.8%) |
Migraine | 202 (20.2%) |
Stroke | 198 (19.8%) |
Transient ischemic attack | 111 (11.1%) |
Epilepsy | 70 (7.0%) |
Multi-infarct dementia | 25 (2.5%) |
Chorea | 13 (1.3%) |
Acute encephalopathy | 11 (1.1%) |
Transient amnesia | 7 (0.7%) |
Cerebral venous thrombosis | 7 (0.7%) |
Cerebellar ataxia | 7 (0.7%) |
Transverse myelopathy | 4 (0.4%) |
Hemiballismus | 3 (0.3%) |
Pulmonary embolism | 141 (14.1%) |
Other pulmonary manifestations | 56 (5.6%) |
Valve thickening/dysfunction | 116 (11.6%) |
Other cardiac manifestations | 153 (15.3%) |
Renal manifestations | 27 (2.7%) |
Gastrointestinal manifestations | 42 (4.2%) |
Livedo reticularis | 241 (24.1%) |
Other cutaneous manifestations | 155 (15.5%) |
Arthralgia | 387 (38.7%) |
Other osteoarticular manifestations | 295 (29.5%) |
Amaurosis fugax | 54 (5.4%) |
Other ophthalmological manifestations | 34 (3.4%) |
8 (0.8%) | |
Thrombocytopenia | 296 (29.6%) |
Hemolytic anemia | 97 (9.7%) |
Preeclampsia | 56 (9.5%) |
Other obstetric manifestations | 41 (7.1%) |
Live birth | 753 (47.7%) |
Other fetal manifestations (fetal loss, premature births) | 827 (52.3%) |
Cumulative clinical features during the evolution of the disease in 1000 patients with APS (adapted [14]).
1. Evidence of involvement of three or more organs, systems, and/or tissues. |
2. Development of manifestations simultaneously or in less than a week. |
3. Confirmation by histopathology of small vessel occlusion in at least one organ or tissue. |
4. Laboratory confirmation of the presence of antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies, and/or anti-beta2-glycoprotein I antibodies). |
Requires all four criteria |
All four criteria, except for only two organs, systems, and/or sites of tissue involvement |
All four criteria, except for the laboratory confirmation at least six weeks apart due to the early death of a patient never tested for aPL before the catastrophic APS |
Criteria 1, 2, and 4 above |
1, 3, and 4 and the development of the third event in more than a week but less than a month, despite anticoagulation. |
In the setting of pregnancy, Obstetric APS (OAPS) is diagnosed if at least one of the clinical criteria and one of the laboratory criteria are met as outlined in Table 4 [1, 20].
Clinical criteria | Laboratory criteria |
---|---|
|
|
Although up to 5% of the population might be positive for aPL antibodies, only a small fraction is diagnosed with APS as per the mentioned criteria [21]. Based on the analysis of 120 full-text papers, the overall estimated aPL frequency in stroke patients of all ages is 13.5% [22]. Sciascia et al. [7], in a systematic review of data from 5217 patients concluded that the overall aPL frequency was estimated as 17.2% for stroke and 11.7% for the transient ischemic attack, and the presence of aPL seems to confer a five-fold higher risk for stroke or TIA when compared with controls. The cumulative prevalence in the Euro-Phospholipid Project Study was 19.8% for stroke and 11.1% for TIA [14], making it the most common and severe arterial complication of APS.
Notably, it has been suggested that more than 20% of strokes in patients younger than 45 years are associated with APS [23], although this estimate may be inflated by referral bias [24]. The presence and magnitude of the ischemic stroke risk associated with aPL in the older population are more evenly split between finding an increased risk and no increased risk. This suggests that aPL may be a more important stroke mechanism in young people whereas, in older populations, other stroke risk factors take on a greater importance.
aPL associated strokes pose a higher risk for women. The Framingham cohort and offspring study found an increased risk of strokes and TIAs for women with high anticardiolipin but not in men [25]. In another study of 34 women under 45 years of age with ischemic strokes and no traditional vascular risk factors, 35% were found to have anticardiolipin antibodies [26].
Another study demonstrated that high serum concentrations of aPL, regardless of other cardiovascular risk factors, were an important predictor of the risk of future stroke and TIA in only females [27]. The presence of anti-β2GP1 antibodies in young women may increase the stroke risk 2.3-fold according to the RATIO study [28].
In terms of traditional vascular risk factors in APS patients, it is debated whether these or the circulating aPL antibodies are responsible for the accelerated atherosclerosis seen in APS. Hypertension is more prevalent in SLE and APS than in the general population. A study showed that hypertension was the only independent risk factor for arterial manifestations, mainly stroke, in APS [29]. The risk of stroke for LA-positive patients was two-fold in smokers and six-fold in smokers receiving oral contraceptives [25]. The Italian Project on Stroke in Young Adults, a prospective study of 1867 patients showed that family history of strokes, migraines with auras, aPL, discontinuation of antiplatelet or antihypertensive medications and increase in at least one traditional vascular risk factor were independent predictors for thromboembolic events [30]. Overall, this emphasizes the importance of aggressively treating all modifiable stroke risk factors like hypertension, diabetes, hypercholesterolemia, obesity, OCP use, and tobacco use to reduce additional thrombotic risks.
A summary of factors that warrant an evaluation of APS in stroke patients is listed in Table 5.
Patient age < 50 years of age |
Female gender |
Lack of traditional vascular risk factors |
Positive family history for arterial or venous thromboses |
Recurrent strokes |
Thrombocytopenia, obstetric complications, venous thromboses, or other arterial thromboses |
SLE or presence of other connective tissue diseases |
Key factors warranting evaluation of antiphospholipid syndrome.
Stroke subtypes in APS may be either thrombotic or cardioembolic depending on the location and size of the occluded vessel [31]. Intracranial stem or branch arterial occlusions and stenosis were reported in 50% of APS patients with stroke [32]. Narrowing of multiple intracranial arteries may occur in APS and indicates vasculopathy rather than vasculitis. Occasionally, there is involvement of the extracranial carotid artery. In a small case series of 17 patients, 32% had extracranial arterial abnormalities [33]. Cardioembolic strokes in APS are associated with left cardiac valvular abnormalities, including irregular thickening of leaflets, non-bacterial vegetations, and valve dysfunction [32]. Stroke subtypes in APS can also vary according to the types of antibodies [34]. Saidi et al. [35], in an analysis of 208 patients with their first stroke, reported that antiphosphatidylserine IgG was associated with cardioembolic strokes, lupus anticoagulant with lacunar strokes, and anticardiolipin IgG and IgM with lacunar, atherosclerotic and cardioembolic strokes. The severity of the thromboembolic event does not relate to the aPL antibody titer.
The type of antibodies present also appears to have an association with increased thrombotic risk. The presence of antiphosphatidylserine antibodies had the highest risk for clinical manifestations of APS, and IgG antiphosphatidylserine antibodies correlated strongly with the presence of lupus anticoagulant. The presence of antiphosphatidylserine antibodies (IgG or IgM) or anti-b2GP-1 (IgG, IgM, or IgA) antibodies improved the specificity for APS over anticardiolipin antibodies alone [36]. In another study, the positive predictive value for antiphosphatidylserine and anti-b2GP-1 antibodies was stronger for arterial thromboses than for venous thromboses [37]. Another study of pregnant women with APS reported that patients with triple aPL positivity (LA, aCL, and anti-B2GPI) and/or previous thromboembolism had an increased likelihood of poor neonatal outcomes than patients with double or single aPL positivity and no thrombosis history [38].
The recurrent risk of stroke in APS patients has been less widely studied as compared to other types of thromboses. Pezzini et al. calculated a cumulative risk of 14% for brain ischemia at 10 years [30]. Recurrent strokes and other thromboembolic events in patients with aPL antibodies have been reported both early (within the first year of an index stroke event) and late (5–10 years) [39]. The initial type of thromboembolic event (i.e. arterial, venous, miscarriage) appears to be the most likely type of event to recur in a given patient according to some studies [40]. The Euro-Phospholipid Project Group reported thrombotic events in 16.6% of patients in the first 5 years of follow-up and in 14.4% in the second 5-year follow-up period. The most common events during follow-up were strokes, TIAs, DVTs, and pulmonary emboli with survival probability at 10 years being 90.7% [14].
The first model to develop a predictive model for aPL associated thrombosis risk in SLE patients was modified in 2013 by Sciascia et al. to include data on clinical manifestations, and risk factors forming a quantitative score called the Global Antiphospholipid Syndrome Score (GAPSS) [41]. This was further modified in 2019 to form the aGAPSS (Adjusted Global Antiphospholipid Syndrome Score) as outlined in Table 6 [42]. The goal of the aGAPSS is to risk-stratify patients based on the likelihood of developing recurrent thrombosis in the setting of APS.
Factor | Point value |
---|---|
Anticardiolipin Antibody IgG/IgM | 5 |
Anti-B2-glycoprotein I IgG/IGM | 4 |
Lupus anticoagulant | 4 |
Hyperlipidemia | 3 |
Arterial hypertension | 1 |
Taken together, screening for APS is indicated in stroke patients who meet even some of the clinical and laboratory criteria and those with recurrent strokes despite maximal medical management and no clear etiology. The goal of these scoring systems is to further refine the risk of recurrent thromboses associated with APS.
Cerebral venous sinus thrombosis (CVST) usually presents with headaches, nausea, vomiting, often associated with seizures, and focal neurological deficits. Papilledema, coma, and death also occasionally contribute to the clinical manifestation of CVST. In patients with CVST, reported frequency of aCL positivity ranges from 7 to 22% [43], and predisposes to CVST at a relatively younger age and to a more extensive cerebral venous involvement [44]. In addition, a higher rate of post-cerebral venous sinus thrombosis headache and more infarctions on brain imaging studies are seen in patients with aPL antibodies than in those without them [45].
While intracranial hemorrhage (ICH) is not a common manifestation of APS, there have been reports of reversible vasoconstriction syndrome (RCVS) [46] which is characterized by thunderclap headaches (severe pain peaking in seconds), and focal neurologic deficits.
Moyamoya disease, a progressive narrowing of cerebral vasculature with collateralization, has also been reported to have associations with APS. Of the 16 cases reported in a small series of moyamoya and aPL, 21% fulfilled APS criteria [47].
Sneddon syndrome is a rare entity that may be considered during workup for APS. It is a chronic disorder, usually non-inflammatory, notable for generalized livedo racemosa (which may be confused with livedo reticularis seen in APS), and recurrent strokes [48]. Livedo racemosa is characterized by a violaceous netlike patterning of the skin similar to the familiar livedo reticularis, although it differs by its location (more generalized and widespread, found not only on the limbs but also on the trunk and/or buttocks). Approximately 40–50% of patients with Sneddon’s syndrome present aPL antibodies, suggesting that some patients should be classified as APS [49].
Cognitive dysfunction has been reported 19–40% in aPL-positive patients [50]. While many believe that the cognitive decline is due to multiple subcortical infarcts, there have been theories that it is multifactorial, with genetic predisposition, antibody specificity, and direct antibody effects as potential contributors [51].
Migraines are the most prevalent neurologic manifestation in APS, estimated prevalence of around 20% [52].
Other rare clinical manifestations of APS include seizures, acute ischemic encephalopathy, transverse myelitis, amaurosis fugax, optic neuropathy, and other neuropsychiatric disorders.
APS has been a recognized cause of cerebrovascular events (CVE) especially in those without classic cardiovascular risk factors. Traditionally, it has been estimated that one in five strokes in patients younger than 45 could be associated with APS, but there have been concerns that this is an over-estimate due to referral bias [53]. Systematic reviews have provided much of our current knowledge on the prevalence of aPL in patients with vascular events, however broad population studies are lacking. One large study evaluating stroke, pregnancy morbidity, myocardial infarction, and deep vein thrombosis estimated that aPL antibodies were present in ∼14% of stroke patients [22].
APS, either primary or secondary, garners consideration especially in young patients with CVE. To address events in the young, the previous study [21] was repeated for those less than 50 years of age and positive aPL was found in 17.4% of cases [54]. Regardless of diagnosis, the presence of any aPL increased the risk of CVE by 5.48-fold for those under the age of 50, and the risk of thrombosis progressively increases with the increasing number of positive antibodies [54]. It has also been reported that patients with stroke and aPL positivity are younger and more likely to be female than patients with strokes who are aPL negative [51]. A similar risk for CVE has been recently reported in another study, where persistently positive aPL increased the risk of CVE by 4.62-fold and where the positive criteria and non-criteria aPL was found in 20/89 (22%) CVE patients [55].
The Euro-Phospholipid Project cataloged the largest group of patients with APS. At the initiation of this study, prevalence data were obtained with 13.1% of patients having a stroke as their presenting manifestation [52]. Stroke was the fourth most common presenting symptom behind deep vein thrombosis, thrombocytopenia, and livedo reticularis. Of the 1000 patients, 204 (about 20%) experienced a stroke at some point during their disease course [52]. Cervera et al. [52] made a delineation regarding age-of-onset, defining “older-onset” APS as diagnosis after the age of 50. Comparatively, the over-50 patients were more likely to have strokes (30%) and were more likely to be male (34%), and were more likely to experience angina pectoris (9%) [52]. These patients were followed over a 10-year time period, and over that time period, 5.3% of the patients experienced a stroke. Stroke was the most prevalent thrombotic event. It was also the 4th leading cause of death in these patients following bacterial infection, myocardial infarction, and malignancy [14].
Patients with APS hospitalized with a stroke also have increased mortality compared to patients without APS [55]. APS has also been identified as an independent risk factor for hemorrhagic transformation of ischemic stroke (OR 2.57, 95%CI 1.14–5.81, p = 0.0228) and extended hospital length of stay [56].
One of the unique aspects of APS is the diversity of types of vasculature involved—arteries and veins, small vessels, and large vessels. Multiple mechanisms of the prothrombotic state have been theorized and will be discussed in Section 4 of this chapter. APS has been implicated in multiple stroke etiologic subtypes including large-artery atherosclerosis, cardio-embolism, and small-vessel occlusion. However, the percentage breakdown between these etiologies has not been consistently reported.
As previously stated, APS is responsible for venous events as well as arterial events. In the cerebrovascular system, these include CVST. APS has been implicated in 6–17% of all cases of CVST and tends to predispose to CVST at a relatively younger age [44].
Vasculopathies, described in detail in Section 2, including Moyamoya and Sneddon’s syndrome, overlap with APS at a rate of 21% and 50% respectively. Reversible cerebral vasoconstriction syndrome (RCVS) has also been described in patients with APS [46].
Other neurologic manifestations of the antiphospholipid syndrome include headache (20%), seizures (8%), and chorea (1.3–4.5%), with less frequent neurological manifestations including parkinsonism (especially progressive supranuclear palsy), dystonia, ballismus, myoclonus, cerebella ataxia, transverse myelitis, cognitive impairments, psychiatric symptoms, and peripheral neuropathy [4, 57].
As outlined in Table 7, some aPL are associated with a higher risk of ischemic stroke than others. Isolated LA positivity induces the greatest individual antibody risk for ischemic stroke [58]. Anti- β2-GPI were also associated with increased risk but to a lesser degree [58]. aCL and antiprothrombin antibodies have been reported variably with some studies showing no increased risk as an independent risk factor [27] while others reported to be independent risk when considering young patients exclusively [58]. As mentioned, triple positivity with positive LA, β2-GPI antibodies and aCL antibodies confers the highest risk [58].
High risk | Moderate risk | Low risk |
---|---|---|
Triple positivity (LA + aCL + anti-β2-GPI) | Isolated aCL when persistently positive in patients with SLE | Isolated anti-β2-GPI positivity |
Isolated LA positivity | Inconsistent and low titer isolated aCL positivity |
Risk for cerebrovascular event based on serologic profile. Adapted [58].
Traditional cardiovascular risk factors also play a role in outcomes for patients with APS. Studies reveal that hypertension and smoking are the risk factors most associated with repeat thrombotic arterial events [59]. Combinations of risk factors have also been shown to increase the risk of repeat events [60]. Prospective studies evaluating the results of risk factor control have yet to be reported.
The RATIO study (Risk of Arterial Thrombosis In relation to Oral contraceptives) identified that the use of oral contraceptives (OCPs) and smoking carried an extremely high risk for women with APS in terms of risk for myocardial infarction and ischemic stroke [28]. The data revealed that the relative risk for ischemic stroke was higher in those who were smoking and in women with OCPs. The odds ratio for ischemic stroke was 43.1 (95%CI 12.2–152.0), which increased to 201.0 (95%CI 22.1–1828.0) in women who used oral contraceptives and 87.0 (14.5–523.0) in those who smoked. In women who had anti- β2-GPI, the risk of ischemic stroke was 2.3 (95%CI 1.4–3.7), but the risk of myocardial infarction was not increased (OR 0.9, 95%CI 0.5–1.6). Neither aCL nor anti-prothrombin antibodies affected the risk of myocardial infarction or ischemic stroke [28].
Vascular thrombosis in APS can affect a wide variety of organ systems, but cerebrovascular thrombosis leading to stroke and transient ischemic attack is the most prevalent and perhaps the most consequential arterial event [61]. In a retrospective study of 135 APS patients, the highest morbidity was linked to neurologic involvement especially due to arterial thrombosis [62]. APS is also an important cause of stroke in the young, but as described can also affect older individuals [60]. The mechanisms of stroke in APS are diverse and include thrombosis in arteries, veins, and the microvasculature, as well as cardioembolism from non-bacterial thrombotic endocarditis.
The pathophysiology of vascular thrombosis in APS is not completely understood, but several studies suggest multiple converging pathways involving not only antibodies but also endothelial cells, platelets, monocytes, coagulation cascade proteins, and complements [63] producing a systemic thrombo-inflammatory state. The presence of aPL is not the sole cause for the significant clinical manifestations of APS as there can be asymptomatic “carriers” [17, 60]. Therefore, as previously mentioned, a “two-hit” hypothesis has been theorized, where the first-hit involves the presence of circulating aPL and associated endothelial dysfunction, and the second-hit presents an inflammatory insult such as trauma, surgery, or infection, leading to upregulation of β2GPI receptors on endothelial cells, as schematically demonstrated in Figure 2.
The pathophysiology of vascular thrombosis in APS is not completely understood, but a 2-hit hypothesis is widely proposed. The first hit involves the presence of circulating aPL and endothelial injury, while the second hit requires an inflammatory insult such as trauma, surgery, or infection, leading to upregulation of beta-2 glycoprotein 1 (β2-GP1) receptors on endothelial cells. The aPLs-β2-GP1 receptor interaction unleashes multiple converging downstream pathways culminating in a thrombo-inflammatory state. VEGF: vascular endothelial growth factor; neutrophil extracellular traps (NETosis); GP: glycoprotein; TF: tissue factor (adapted [
Even though aPL can be detected either by clotting tests, such as LA, or by an ELISA, such as aCL and anti-β2GPI, they are predominantly directed against β2GPI [17] and prothrombin [64]. Other important antigens recognized by aPL are annexin V, phosphatidylethanolamine, and phosphatidylserine [65]. Mechanistically these autoantibodies target phospholipid-binding plasma proteins bound to the surface of vascular endothelial cells and thrombocytes [60]. Plasma proteins predominantly bind to phosphatidylserine [17]. Normally located in the inner surface of cell membranes, phosphatidylserine becomes externalized when endothelial cells, platelets, and monocytes are activated. The avidity with which β2GPI binds to phosphatidylserine is further enhanced by the ‘β2GPI’- ‘β2GPI antibody dimerization’ [66]. The downstream effect of β2GPI antibodies on endothelial cells and monocytes includes increased expression of tissue factor and thromboxane A2 which trigger the extrinsic coagulation pathway [64, 67]. Furthermore, the antibody binding inhibits the tissue factor pathway inhibitor and protein C activity [64, 67]. Taken together, the net effect is the synergistic production of a prothrombotic state. Endothelial cells, upon stimulation with aPL, also downregulate their nitric oxide production and increase the surface expression of adhesion molecules such as E-selectin leading to pro-inflammatory and pro-coagulation endothelial phenotype [17, 57, 67, 68]. This antibody-induced endothelial injury can lead to intimal hyperplasia, micro-vasculopathy, and accelerated atherosclerosis [69]. Activated platelets increase their surface expression of GPIIb-IIIa, synthesis of thromboxane A2 and platelet factor-4a, all acting to facilitate thrombosis [67]. Activation of neutrophils with accompanying release of Neutrophil Extracellular Traps (NETosis) and IL-8 may also play a role [67]. Annexin V, a natural anticoagulant, binds to phosphatidylserine (a procoagulant) forming an anticoagulant shield in the physiologic state in APS, this shield is disrupted tipping the system in favor of coagulation [70]. Upregulation in the mTOR (mechanistic target of rapamycin) pathway on endothelial cells may partly explain the microvascular thrombosis seen in APS.
In addition to vascular thrombosis, up to one-third of patients with APS develop non-bacterial thrombotic endocarditis (NBTE) in which there is a deposition of sterile platelet thrombi on heart valves, particularly the mitral and aortic valves, which can be a source of cardioembolic strokes [66].
Population and family studies, as well as animal studies, have suggested genetic disposition may be relevant to the development of APS. Like many autoimmune disorders, predisposition to APS has been mapped to genes in the major histocompatibility complex (MHC), among others. Also, epigenetic phenomena such as altered microRNA biogenesis in neutrophils, leading to accelerated atherosclerosis, have been implicated in APS [63].
The initial workup for stroke in the setting of APS is consistent with that of other stroke etiologies. Specifically, a multisystem approach evaluating from “
What raises the suspicion for APS in stroke? When should it be considered that more information and studies are needed besides the typical workup usually undertaken? The most pertinent situation would be when a younger patient (<50 years) presented with a thrombotic stroke without identified classic risk factors for ischemic/embolic stroke [71]. Initial workup may reveal exam and laboratory findings that may raise the concern for APS as listed in Table 8. Notably, subtle renal, cardiac, hematologic, and dermatologic system alterations can be indicative. Further, a family history of early-onset stroke, clotting, or other systemic features should be queried. Absence of typical risk factors including hypertension, diabetes, atrial fibrillation, or known history of coagulopathy (e.g. protein C deficiency, protein S deficiency, antithrombin III), among others, further increases the consideration for APS. Notably, as many as 17% of cardiovascular events in those under 50 reveal aPL antibodies and up to 22% including anticardiolipin antibodies [54].
1. Hematologic |
2. Neurologic
|
3. Dermatologic
|
4. Cardiac
|
5. Renal
|
Other important clinical signs of APS not noted in Sapporo criteria, by body system. Adapted [63].
Of note, without suggestion of underlying coagulopathy or clinical findings (see Table 8) a young patient without classic risk factors, testing for many coagulopathies is not routinely performed. When performed, there is also the question of whether this workup needs to occur in the inpatient setting, during the patient’s admission for stroke, or if it can be done post-discharge. When considering this, the most important question is: Will any findings acutely change management? It should also be noted that for a positive diagnosis APS testing needs to occur multiple times over a 3 month or longer time period. If considering the APS diagnosis, formal hematology and/or rheumatology consult is recommended. In general, the recommendation for inpatient vs. outpatient is that some workup may be deferred if necessary, to the outpatient setting, either under the care of the patient’s primary physician/provider, neurologist, hematologist, or rheumatologist.
Consistent with all stroke patients, every patient should receive standard stroke workup testing including brain imaging (CT brain, MRI brain), vessel imaging of the head, neck, and great vessels of the chest (CTA, MRA), cardiac imaging including a transthoracic echocardiogram (TTE) and laboratory testing (CMP, CBC, PT/INR, aPTT, TSH, HgbA1C, lipid profile). A bubble study with the TTE should be considered if a paradoxical embolus from a DVT is on the differential. It is also recommended to obtain basic inflammatory markers such as sedimentation rate (ESR) and C-reactive protein (CRP) to evaluate for suggestion of diffuse inflammatory disease [24].
Transesophageal echocardiogram (TEE) should also be considered if the etiology remains uncertain, this is due to the increased frequency of valvular abnormalities in the setting of APS that may include irregular nodules/vegetations most commonly on the atrial side of the mitral valve or vascular side of the aortic valve, or if thickening of the valves is noted on TTE. Most commonly, the left side of the heart is the affected side with the mitral valve more commonly affected compared to the aortic valve. These cardiac changes are postulated to be due to immune complex damage and fibrosis [72].
If APS is being considered, it is recommended that while inpatient with the acute stroke the patient should have all antiphospholipid antibodies checked, according to the revised Sapporo laboratory criteria (see Table 1). Notably, this includes ELISA IgM/IgG for anticardiolipin (aCL) with a positive test showing medium to high titers (>40 GPL/MPL units or >99th percentile), which will need to be confirmed on at least two or more occasions, 12-weeks apart. Lupus anticoagulant (LA) should also be checked by two tests including dilute Russell viper venom time (dRVVT) and LA-sensitive PTT (PTT-LA)), again conformed on at least two occasions, 12-weeks apart. Lastly, an ELISA IgM/IgG for anti-beta2-glycoprotein I (β2GPI) should also be tested, with a positive value determined by titer in the 99th percentile, and again, should be tested on at least two occasions 12-weeks apart.
At least one clinical criterion (in the context of this chapter, most likely stroke) and one laboratory criterion should be met to diagnosis APS. As described, these tests are done 12-weeks apart, so the first set of lab tests will be performed inpatient and then the second 12-weeks later, typically performed in the outpatient setting. As outlined in Table 8, if the patient does not meet revised Sapporo criteria, APS may still be diagnosed if clinical suspicion remains high based on multi-system abnormalities and if further etiologies are not identified [64].
If a patient inconsistently tests positive for APS, it may be warranted to also check for other autoimmune diseases, namely systemic lupus erythematosus (SLE), as up to 36% of those with APS will be positive for SLE. Having both APS and SLE increases the risk for stroke beyond having only one or the other [31].
As described above, there are 3 primary antibody tests for APS including aCL, LA, and β2GPI. Anticardiolipin (aCL) testing was first developed as a test for syphilis in the 1900s [71]. The aCL antibody was found not to be specific to just syphilis, thus its utility as a test for APS was also found after many false-positive syphilis tests showed an increased risk for thrombotic events. The tests presently use tissue derived from bovine tissue. Both IgG and IgM are evaluated by ELISA for the presence of aCL antibodies. Notably, due to cross-reactivity as discussed with syphilis, the presence of aCL does not alone confirm APS.
Lupus anticoagulant (LA) is a test for immunoglobulins that while associated with thrombosis, are associated with preventing coagulation in vivo. The process for testing LA is three tests including screening (usually with aPTT or dRVVT, clotting of phospholipid factors), mixing (correct with normal plasma), and confirmation (shortening prolongation with added phospholipid) [67]. Once again, LA by itself cannot confirm APS due to cross-reactivity. LA testing is outlined in Figure 3.
Testing for lupus anticoagulant (Adapted [
Anti-β2 glycoprotein I (β2GPI) enzyme-linked immunosorbent assay (ELISA) testing is the last of the trio of tests for APS. There are 5 main domains of the β2GPI, labeled DI through DV. Anti-β2GPI largely targets domain I (DI). When this domain is targeted, it has been shown an association with thrombosis. The other domains DII through DV being targeted have not been shown to have as strong a connection for promoting thrombosis. Of note, there are some more rare entities that may also raise anti-β2GPI levels, such as leishmaniasis, leptospirosis, or leprosy. For APS, the associated antibodies are against the IgG form, whereas other elevates of anti-β2GPI may be directed towards the IgM variety [73].
Unless the patient presents with a prior history of APS, the diagnosis of APS will likely be in question during the acute and subacute stroke window. This is because APS by laboratory criteria needs to be performed 12-weeks apart with two positive tests to confirm. That said, a patient that presents with a stroke and has one or more laboratory results that are concerning for APS (positive LA, aCL, anti-β2GPI), there is a question if confirming APS would change acute management. Oftentimes, the answer is yes; this even in the setting of likely APS, because thrombosis can be multifactorial and can progress between confirmatory APS testing [67]. As such, management should focus on appropriate treatment for the source of the stroke. For example, if the source is cardioembolic, the timing of initiation of anticoagulation should be considered, weighing the risk of a second embolic event while not on indicated therapy versus the risk of hemorrhagic conversion of the primary infarct.
Once the workup for APS is complete, and if positive, the next logical step is to address treatment. However, prior to addressing treatment, let us first consider if APS is a primary risk factor for stroke risk. Numerous studies have been performed to address this question, culminating with a meta-analysis evaluating 15 different studies in aggregate [54]. In this evaluation, 13 of the 15 studies reported a significant association between a CVE and aPL antibodies with a cumulative odds ratio of 5.48 [54]. While this study provides insight into primary event risk, a follow-up question relates to the risk of APS with recurrent stroke. A second meta-analysis was completed looking at 8 studies to answer this question, demonstrating no statistically significant risk of recurrent ischemic stroke among APS patients [74]. Understanding why one meta-analysis demonstrated a link between aPL antibodies and single ischemic events, while another did not show a link with recurrent events remains challenging to understand. One hypothesis used to explain these incongruent findings is that clinical events do not occur frequently occur despite the presence of the antibodies, suggesting that treatment and/or lifestyle modifications after a first stroke affect the chance of a second event [74, 75]. Therefore, an understanding that APS is associated with the single cerebral vascular event, and that treatment affects the chance of a second event, indicates that secondary prevention is highly warranted.
Knowing that therapy is indicated, we can now evaluate various treatments on the risk of thrombosis in the setting of APS. In those individuals without any other risk factors, the risk of thrombosis is less than 1% per year [76, 77]. In this group, when they do present with a thrombus, it is normally in the setting of another thrombotic risk factor, such as cancer, surgery, pregnancy, estrogen use, acute infection, smoking, and hypertension. On the other hand, the risk of thrombosis can be as high as 5% per year in individuals with a persistent moderate high-risk profile including aPL antibodies and a systemic autoimmune disease [78]. Therefore, with the risk of thrombosis being so variable, sometimes as low as 1% or other times as high as 5%, the question of optimal prevention strategies can be challenging.
Regarding primary prevention (before a stroke or vascular event) the answer remains controversial with only scant data based on prospective trials [79]. Some of these trials have demonstrated a decrease in thrombosis with the use of aspirin. For example, a meta-analysis of 11 mostly observational studies demonstrated a 2-fold risk reduction in the first thrombotic event with a more significant effect in those with arterial thrombosis [79]. Post subgroup analysis of only prospective trials demonstrated there was no significant difference between aspirin and those not treated [79]. Therefore, with conflicting data on aspirin, one may ask could there be a benefit with the use of anticoagulation as well as aspirin for primary prevention. While the data was limited, one primary prevention study evaluated the use of aspirin alone vs. aspirin plus anticoagulation in 166 patients, demonstrating no significant difference in terms of the amount of thrombotic events between groups, with an increased risk of bleeding in the aspirin plus warfarin arm [80]. Therefore, given the increased bleeding risk, the use of aspirin and warfarin in combination is not recommended for primary prevention, with the question of aspirin use in isolation remaining. Many agencies have weighed in on this subject including the 13th International Congress on Antiphospholipid Antibodies as well as the European League Against Rheumatism making recommendations suggesting the use of aspirin in high-risk antiphospholipid profiles, those with other thrombotic risk factors, as well as those with SLE [58, 81]. Even with these recommendations, one must also consider the risk of bleeding with the use of aspirin. One meta-analysis looking at six randomized control trials showed an association of increased annual risk of major bleeding in those patients using aspirin with hypertension, age > 65, diabetes, and male sex being the most significant associated risk factors [82].
In summary, the decision to use primary prevention remains an individualized choice based on a patient-centric decision. Overall, though one should consider the use of primary prevention with aspirin in those with cardiac risk factors, high risk antiphospholipid antibody profile, presence of other thrombotic risk factors and in the presence of other autoimmune disease always ensuring a thorough risk benefit analysis is done with concern for bleeding. See Figure 4 for breakdown of treatment option algorithm.
Treatment options algorithm (adapted [
Knowing the indications for the use of primary prophylaxis we now consider secondary prophylaxis. Data regarding the need for secondary prophylaxis specifically in previous arterial thrombi remains scant without any consensus. For example, one study demonstrated the use of warfarin with a goal INR of 1.4–2.8 was not superior to full dose aspirin 325 mg alone for stroke prevention, with concerns that this study was flawed due to transient positivity of aPL antibodies [27]. Another study evaluating 20 patients with ischemic stroke demonstrated that the use of low-dose aspirin and warfarin with a goal INR of 2–3 was superior to low-dose aspirin alone in the prevention of further arterial thrombi [11]. While two other studies demonstrated that for older patients with stroke, and a single test showing low titers of anticardiolipin antibodies, that aspirin may be as effective as warfarin [27, 83]. With this conflicting data, there remains no consensus statement on secondary prophylaxis with many agencies weighing in on this subject. For example, the 13th International Congress on Antiphospholipid Antibodies as well as the European League Against Rheumatism both recommended secondary prophylaxis with high-intensity warfarin with an INR > 3 or low dose aspirin combined with moderate-intensity warfarin with an INR from 2 to 3 [58, 81]. Both agencies decided on using a goal INR of >3 for warfarin because in previous studies evaluating different doses of warfarin in treating thrombi, relatively few patients with arterial thrombi were enrolled [84, 85]. Overall, data remains scarce and guidelines are based upon a consensus of expert opinion. In those with recurrent arterial events, some recommend increasing target INR level and or switching to low molecular weight heparin with the addition of other adjective therapies to include statins [86].
In summary, the decision on which patient to treat and which agent to use for secondary prophylaxis with arterial thrombi remains a patient-centric decision. Those with high-risk aPL profiles, presence of other systemic autoimmune diseases, and or other risk factors for thrombus would likely benefit from treatment with either aspirin and warfarin with a goal 2–3 or warfarin alone with a goal INR 3–4. Those with recurrent events would likely benefit from increasing the INR goal or if not feasible switching to low molecular weight heparin. Moving forward it would be beneficial to validate a risk stratification model to identify those with arterial thrombosis who would benefit from more aggressive treatment [67]. See Figure 5 demonstrates a treatment options algorithm.
Arterial versus venous thrombus treatment options algorithm (adapted [
Now knowing the indications and treatment options for the use in secondary arterial prophylaxis we now move on to secondary venous prophylaxis, which in the case of stroke would be beneficial in treating paradoxical emboli. Much different from that in arterial secondary prophylaxis, there is more of a consensus regarding the treatment of secondary venous prophylaxis using warfarin with a goal INR of 2–3 showing a decrease in recurrent venous events of 80–90% [57, 87]. Some studies have evaluated the use of higher intensity anticoagulation with a goal INR of 3.1–4.5 showing no reduced risk in thrombosis, but a significant excess of minor bleeding [84, 85].
Therefore, with the above data, we can safely say in summary for secondary prevention for venous thrombi in those with a chance of paradoxical emboli treatment with warfarin with a goal INR of 2–3 is indicated. See Figure 5 for a treatment options algorithm.
Following the basics of both primary and secondary prevention, one may question other anticoagulation options as adjuvant therapies. Regarding the use of direct oral anticoagulants (DOACs) there remains insufficient evidence with data suggesting an increased risk of thrombosis [88]. For example, two studies demonstrated no difference in the rate of venous thromboembolism and an increased risk of arterial thrombotic with the use of rivaroxaban over warfarin [89, 90]. Looking at this data more closely, a meta-analysis of these two studies did not find an increased risk of thrombosis in patients treated with rivaroxaban over warfarin at a 6 month follow up, however for unclear reasons, almost 3/4 of the thrombi occurred post the 6 months follow up [39]. Given the lack of prospective data, the utility of DOACs in the treatment of thrombus formation remains uncertain.
Beyond DOACs, other adjuvant therapies have been studied including statins and hydroxychloroquine. With statins being a mainstay of treatment post-stroke, it would not be unreasonable to think that they may be beneficial in APS, potentially exhibiting pleiotropic effects including anti-inflammatory, antithrombotic, and as well as the expected lipid-lowering potential [13]. To date, there have been no randomized controlled trials looking at the efficacy in this group of patients. One study however did look at the levels of pro-inflammatory and prothrombotic markers post use of Fluvastatin, which were significantly decreased suggesting their benefit in APS [91]. At this time without a randomized control trial, the 15th International Congress on Antiphospholipid Antibodies has recommended the use of statins in those with high cardiovascular risks and or recurrent thrombosis despite adequate AC [88]. Regarding the use of hydroxychloroquine, similar to statins in addition to its immunomodulatory effect, it also has antithrombotic properties making it a good candidate as adjunctive therapy [88]. Two studies have been performed demonstrating differing results regarding treatment with hydroxychloroquine plus aspirin vs. aspirin alone. The first demonstrated no difference between rates of thrombosis between both groups [92]. The other demonstrated a significantly lower thrombotic rate compared to standard of care alone, in addition to down-trending antibody titers [93]. These data suggest that both statins and hydroxychloroquine could be beneficial as adjunctive therapies in specific situations, although more data is needed for consensus.
Throughout this section, we have addressed the need for primary and secondary prevention, but one question left unanswered is safety as associated with therapy cessation. Unfortunately, there remains a multitude of answers to this question, hence each case should be considered independently. In those with a history of arterial thrombotic events, the risk of repeat thrombus formation off anticoagulation is too high and therefore indefinite anticoagulation is warranted [94]. In those with a history of transient positivity of antiphospholipid antibodies who eventually become negative based on two separate studies, one can consider stopping anticoagulation [95, 96]. Specifically, this would be associated with those who only have primary APS with persistently negative antibodies where if there was a thrombotic event it occurred in association with a transient risk factor including pregnancy or immobilization as examples [96]. In these cases, it is thought that the antibodies do not play a pathogenic role, but rather are a “phenomenon”. Therefore, some have recommended a 3–6-month course of anticoagulation with consideration to look for residual thrombus, which has been shown to increase the rate of recurrence by 50% [94]. Notably, the data and recommendations regarding stopping anticoagulation are based upon two small case series. Therefore, with such insufficient data, unless the risk of anticoagulation outweighs the benefit it would not be recommended to stop anticoagulation in those that become persistently negative.
Throughout this section we have addressed both preventions of stroke in APS, but what if someone should fail prevention and come in with an acute stroke. The answer to this question unlike many of the other is simple. Acute management is no different than those with or without APS [97]. Lastly, as described, APS often requires treatment with anticoagulant medications such as heparin to reduce the risk of further episodes of thrombosis and improve the prognosis of pregnancy. Warfarin (brand name Coumadin) should not be used during pregnancy because it crosses the placenta and is teratogenic. Unfractionated heparin (UFH) and low molecular weight heparin do not cross the placenta and are safe for the fetus, but long-term treatment with UFH is problematic because of its inconvenient administration, the need to monitor anticoagulant activity, and because of its potential side effects, such as heparin-induced thrombocytopenia and osteoporosis [98].
Thromboses of the cerebral arterial and venous systems are a common manifestation of APS leading to ischemic and/or hemorrhagic stroke. APS has been a recognized cause of CVE especially in those without classic cardiovascular risk factors. It has been estimated that one in five strokes and patients younger than 45 could be associated with APS and some newer studies show that APL antibodies are present in approximately 14% of stroke patients. Persistently elevated APL seems to increase the risk for CV by at least fourfold. Stroke is the fourth most common presenting symptom behind deep venous thrombosis, thrombocytopenia, and livedo reticularis. The recurrent risk of stroke in APS patients has been less widely studied as compared to other types of thromboses, however, cumulative risk of 14% for brain ischemia at 10 years has been reported. APS increases stroke risk via many mechanisms including hypercoagulability, inflammation, accelerated atherosclerosis, and cardiac manifestations, among others. Mechanistically these lead to in-situ clot formation and/or embolic phenomena. Physicians must carefully consider all these potential mechanisms when evaluating and treating stroke patients to achieve both optimal short- and long-term outcomes. While the exact underlying pathophysiology of APS remains uncertain, underlying genetics in the setting of a triggering event (e.g., surgery, trauma, infection) is believed to play a key role in the development of the disease. While primary and secondary prevention recommendations continue to evolve, each case should be considered independently to achieve optimal results. Results from more randomized control trials are needed to further infer upon the ever-evolving consensus guidelines. For the time being, the decision to use primary and/or secondary prevention therapies, and of which type, will continue to be an individualized patient-centric decision requiring careful interpretation of test results with multispecialty (neurology, hematology, rheumatology) input.
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H. Gulrez, Saphwan Al-Assaf and Glyn O Phillips",authors:[{id:"58120",title:"Prof.",name:"Saphwan",middleName:null,surname:"Al-Assaf",slug:"saphwan-al-assaf",fullName:"Saphwan Al-Assaf"}]},{id:"13254",doi:"10.5772/13474",title:"Insight Into Adsorption Thermodynamics",slug:"insight-into-adsorption-thermodynamics",totalDownloads:7142,totalCrossrefCites:88,totalDimensionsCites:259,abstract:null,book:{id:"25",slug:"thermodynamics",title:"Thermodynamics",fullTitle:"Thermodynamics"},signatures:"Papita Saha and Shamik Chowdhury",authors:[{id:"13943",title:"Dr.",name:"Papita",middleName:null,surname:"Saha",slug:"papita-saha",fullName:"Papita Saha"},{id:"24184",title:"Mr.",name:"Shamik",middleName:null,surname:"Chowdhury",slug:"shamik-chowdhury",fullName:"Shamik Chowdhury"}]},{id:"35261",doi:"10.5772/34233",title:"Anisotropic Mechanical Properties of ABS Parts Fabricated by Fused Deposition Modelling",slug:"anisotropic-mechanical-properties-of-abs-parts-fabricated-by-fused-deposition-modeling-",totalDownloads:7260,totalCrossrefCites:114,totalDimensionsCites:240,abstract:null,book:{id:"1982",slug:"mechanical-engineering",title:"Mechanical Engineering",fullTitle:"Mechanical Engineering"},signatures:"Constance Ziemian, Mala Sharma and Sophia Ziemian",authors:[{id:"89554",title:"Dr.",name:"Mala",middleName:null,surname:"Sharma",slug:"mala-sharma",fullName:"Mala Sharma"},{id:"98759",title:"Dr.",name:"Constance",middleName:null,surname:"Ziemian",slug:"constance-ziemian",fullName:"Constance Ziemian"},{id:"137165",title:"Ms.",name:"Sophia",middleName:null,surname:"Ziemian",slug:"sophia-ziemian",fullName:"Sophia Ziemian"}]},{id:"8446",doi:"10.5772/39538",title:"2 µm Laser Sources and Their Possible Applications",slug:"2-m-laser-sources-and-their-possible-applications",totalDownloads:12049,totalCrossrefCites:138,totalDimensionsCites:218,abstract:null,book:{id:"3161",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",title:"Frontiers in Guided Wave Optics and Optoelectronics",fullTitle:"Frontiers in Guided Wave Optics and Optoelectronics"},signatures:"Karsten Scholle, Samir Lamrini, Philipp Koopmann and Peter Fuhrberg",authors:[{id:"4951",title:"Dr.",name:"Karsten",middleName:null,surname:"Scholle",slug:"karsten-scholle",fullName:"Karsten Scholle"},{id:"133366",title:"Prof.",name:"Samir",middleName:null,surname:"Lamrini",slug:"samir-lamrini",fullName:"Samir Lamrini"},{id:"133370",title:"Prof.",name:"Philipp",middleName:null,surname:"Koopmann",slug:"philipp-koopmann",fullName:"Philipp Koopmann"},{id:"133371",title:"Mr.",name:"Peter",middleName:null,surname:"Fuhrberg",slug:"peter-fuhrberg",fullName:"Peter Fuhrberg"}]},{id:"27163",doi:"10.5772/31200",title:"Synergisms between Compost and Biochar for Sustainable Soil Amelioration",slug:"synergism-between-biochar-and-compost-for-sustainable-soil-amelioration",totalDownloads:6042,totalCrossrefCites:68,totalDimensionsCites:170,abstract:null,book:{id:"873",slug:"management-of-organic-waste",title:"Management of Organic Waste",fullTitle:"Management of Organic Waste"},signatures:"Daniel Fischer and Bruno Glaser",authors:[{id:"84418",title:"Prof.",name:"Bruno",middleName:null,surname:"Glaser",slug:"bruno-glaser",fullName:"Bruno Glaser"},{id:"96141",title:"Mr.",name:"Daniel",middleName:null,surname:"Fischer",slug:"daniel-fischer",fullName:"Daniel Fischer"}]}],mostDownloadedChaptersLast30Days:[{id:"35255",title:"Mechanical Transmissions Parameter Modelling",slug:"mechanical-transmissions-parameter-modelling",totalDownloads:7279,totalCrossrefCites:1,totalDimensionsCites:2,abstract:null,book:{id:"1982",slug:"mechanical-engineering",title:"Mechanical Engineering",fullTitle:"Mechanical Engineering"},signatures:"Isad Saric, Nedzad Repcic and Adil Muminovic",authors:[{id:"101313",title:"Prof.",name:"Isad",middleName:null,surname:"Saric",slug:"isad-saric",fullName:"Isad Saric"}]},{id:"67558",title:"Polymerase Chain Reaction (PCR): Principle and Applications",slug:"polymerase-chain-reaction-pcr-principle-and-applications",totalDownloads:10511,totalCrossrefCites:6,totalDimensionsCites:15,abstract:"The characterization of the diversity of species living within ecosystems is of major scientific interest to understand the functioning of these ecosystems. It is also becoming a societal issue since it is necessary to implement the conservation or even the restoration of biodiversity. Historically, species have been described and characterized on the basis of morphological criteria, which are closely linked by environmental conditions or which find their limits especially in groups where they are difficult to access, as is the case for many species of microorganisms. The need to understand the molecular mechanisms in species has made the PCR an indispensable tool for understanding the functioning of these biological systems. A number of markers are now available to detect nuclear DNA polymorphisms. In genetic diversity studies, the most frequently used markers are microsatellites. The study of biological complexity is a new frontier that requires high-throughput molecular technology, high speed computer memory, new approaches to data analysis, and the integration of interdisciplinary skills.",book:{id:"7728",slug:"synthetic-biology-new-interdisciplinary-science",title:"Synthetic Biology",fullTitle:"Synthetic Biology - New Interdisciplinary Science"},signatures:"Karim Kadri",authors:[{id:"290766",title:"Dr.",name:"Kadri",middleName:null,surname:"Karim",slug:"kadri-karim",fullName:"Kadri Karim"}]},{id:"62059",title:"Types of HVAC Systems",slug:"types-of-hvac-systems",totalDownloads:12245,totalCrossrefCites:8,totalDimensionsCites:14,abstract:"HVAC systems are milestones of building mechanical systems that provide thermal comfort for occupants accompanied with indoor air quality. HVAC systems can be classified into central and local systems according to multiple zones, location, and distribution. Primary HVAC equipment includes heating equipment, ventilation equipment, and cooling or air-conditioning equipment. Central HVAC systems locate away from buildings in a central equipment room and deliver the conditioned air by a delivery ductwork system. Central HVAC systems contain all-air, air-water, all-water systems. Two systems should be considered as central such as heating and cooling panels and water-source heat pumps. Local HVAC systems can be located inside a conditioned zone or adjacent to it and no requirement for ductwork. Local systems include local heating, local air-conditioning, local ventilation, and split systems.",book:{id:"6807",slug:"hvac-system",title:"HVAC System",fullTitle:"HVAC System"},signatures:"Shaimaa Seyam",authors:[{id:"247650",title:"M.Sc.",name:"Shaimaa",middleName:null,surname:"Seyam",slug:"shaimaa-seyam",fullName:"Shaimaa Seyam"},{id:"257733",title:"MSc.",name:"Shaimaa",middleName:null,surname:"Seyam",slug:"shaimaa-seyam",fullName:"Shaimaa Seyam"},{id:"395618",title:"Dr.",name:"Shaimaa",middleName:null,surname:"Seyam",slug:"shaimaa-seyam",fullName:"Shaimaa Seyam"}]},{id:"70315",title:"Some Basic and Key Issues of Switched-Reluctance Machine Systems",slug:"some-basic-and-key-issues-of-switched-reluctance-machine-systems",totalDownloads:1238,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Although switched-reluctance machine (SRM) possesses many structural advantages and application potential, it is rather difficult to successfully control with high performance being comparable to other machines. Many critical affairs must be properly treated to obtain the improved operating characteristics. This chapter presents the basic and key technologies of switched-reluctance machine in motor and generator operations. The contents in this chapter include: (1) structures and governing equations of SRM; (2) some commonly used SRM converters; (3) estimation of key parameters and performance evaluation of SRM drive; (4) commutation scheme, current control scheme, and speed control scheme of SRM drive; (5) some commonly used front-end converters and their operation controls for SRM drive; (6) reversible and regenerative braking operation controls for SRM drive; (7) some tuning issues for SRM drive; (8) operation control and some tuning issues of switched-reluctance generators; and (9) experimental application exploration for SRM systems—(a) wind generator and microgrid and (b) EV SRM drive.",book:{id:"8899",slug:"modelling-and-control-of-switched-reluctance-machines",title:"Modelling and Control of Switched Reluctance Machines",fullTitle:"Modelling and Control of Switched Reluctance Machines"},signatures:"Chang-Ming Liaw, Min-Ze Lu, Ping-Hong Jhou and Kuan-Yu Chou",authors:[{id:"37616",title:"Prof.",name:"Chang-Ming",middleName:null,surname:"Liaw",slug:"chang-ming-liaw",fullName:"Chang-Ming Liaw"},{id:"306461",title:"Mr.",name:"Min-Ze",middleName:null,surname:"Lu",slug:"min-ze-lu",fullName:"Min-Ze Lu"},{id:"306463",title:"Mr.",name:"Ping-Hong",middleName:null,surname:"Jhou",slug:"ping-hong-jhou",fullName:"Ping-Hong Jhou"},{id:"306464",title:"Mr.",name:"Kuan-Yu",middleName:null,surname:"Chou",slug:"kuan-yu-chou",fullName:"Kuan-Yu Chou"}]},{id:"70874",title:"Social, Economic, and Environmental Impacts of Renewable Energy Resources",slug:"social-economic-and-environmental-impacts-of-renewable-energy-resources",totalDownloads:4854,totalCrossrefCites:27,totalDimensionsCites:51,abstract:"Conventional energy source based on coal, gas, and oil are very much helpful for the improvement in the economy of a country, but on the other hand, some bad impacts of these resources in the environment have bound us to use these resources within some limit and turned our thinking toward the renewable energy resources. The social, environmental, and economical problems can be omitted by use of renewable energy sources, because these resources are considered as environment-friendly, having no or little emission of exhaust and poisonous gases like carbon dioxide, carbon monooxide, sulfur dioxide, etc. Renewable energy is going to be an important source for power generation in near future, because we can use these resources again and again to produce useful energy. Wind power generation is considered as having lowest water consumption, lowest relative greenhouse gas emission, and most favorable social impacts. It is considered as one of the most sustainable renewable energy sources, followed by hydropower, photovoltaic, and then geothermal. As these resources are considered as clean energy resources, they can be helpful for the mitigation of greenhouse effect and global warming effect. Local employment, better health, job opportunities, job creation, consumer choice, improvement of life standard, social bonds creation, income development, demographic impacts, social bonds creation, and community development can be achieved by the proper usage of renewable energy system. Along with the outstanding advantages of these resources, some shortcomings also exist such as the variation of output due to seasonal change, which is the common thing for wind and hydroelectric power plant; hence, special design and consideration are required, which are fulfilled by the hardware and software due to the improvement in computer technology.",book:{id:"7636",slug:"wind-solar-hybrid-renewable-energy-system",title:"Wind Solar Hybrid Renewable Energy System",fullTitle:"Wind Solar Hybrid Renewable Energy System"},signatures:"Mahesh Kumar",authors:[{id:"309842",title:"Mr.",name:"Kamlesh",middleName:null,surname:"Kumar",slug:"kamlesh-kumar",fullName:"Kamlesh Kumar"}]}],onlineFirstChaptersFilter:{topicId:"11",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82396",title:"Fluid Inventory Models under Markovian Environment",slug:"fluid-inventory-models-under-markovian-environment",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.104183",abstract:"Today’s products are subject to fast changes due to market conditions, short life cycles, and technological advances. Thus, an important problem in inventory planning is how to effectively manage the inventory control in a dynamic and stochastic environment. The traditional Economic Order Quantity (EOQ) and Economic Production Quantity (EPQ) both are widely and successfully used models of inventory management. However, both models assume constant and fixed parameters over time. Unfortunately, most of these assumptions are unrealistic. In this study, we generalize the EOQ and EPQ models and study production-inventory fluid models operating in a stochastic environment. The inventory level increases or decreases according to a fluid-flow rate modulated by an n-state continuous time Markov chain (CTMC). Our main objective is to minimize the expected discounted total cost which includes ordering, purchasing, production, set up, holding, and shortage costs. Applying regenerative theory, optional sampling theorem (OST) to the multi-dimensional martingale and fluid flow techniques, we develop methods to obtain explicit formulas for these cost functionals. As such, we provide managers with a useful framework and an efficient and easy-to-implement tool to coop with different demand–supply patterns.",book:{id:"11169",title:"Logistics Engineering",coverURL:"https://cdn.intechopen.com/books/images_new/11169.jpg"},signatures:"Yonit Barron"},{id:"82326",title:"Probabilistic Risk Assessments for Static Equipment Integrity",slug:"probabilistic-risk-assessments-for-static-equipment-integrity",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.105550",abstract:"The mechanical integrity of batch-produced machinery is successfully safeguarded using online condition monitoring and reliability theory principles. However, the integrity of nonreplaceable static equipment (pressure vessels, cranes, bridges, and other critical infrastructure) is still widely assured and managed using basic equations (e.g., safety factors and design loads), with no or little regard to the probabilistic nature of their operational damage. The gap between the deterministic “remnant life” assumptions and the probabilistic reality restrains the implementation of new asset integrity technologies (advanced condition monitoring and asset management) because these novel tools are not supported by a numeric cost/benefit analysis in many practical cases. The latter is impossible to implement confidently, while the probability of failure (PoF) versus time remains unquantified. The solution to this problem is holistic and logical: individual equipment integrity analysis now needs to be upgraded to the probabilistic terms at all the stages of life. Even well-known asset integrity technologies can help achieve this goal, providing that they are considered and utilized from the standpoint of harmonizing and aligning their outputs with risk owner’s actual decision-making. This chapter shows real-life case studies to briefly illustrate how the existing integrity engineering tools can be advanced via further PoF considerations, in order to provide the outputs needed for a cost/benefit-based confident and compliant risk control.",book:{id:"11528",title:"Maintenance Management - Current Challenges, New Developments, and Future Directions",coverURL:"https://cdn.intechopen.com/books/images_new/11528.jpg"},signatures:"Yury Sokolov"},{id:"1083885",title:"Design and Planning Robust and Competitive Supply Chains",slug:null,totalDownloads:1,totalDimensionsCites:0,doi:"10.5992/intechopen.1000208",abstract:'
In recent years, supply chains in the manufacturing industry have become more and more complicated, and many cases of supply chain disruptions due to natural disasters have been confirmed. It is necessary for manufacturers to build a system that can help them alleviate losses and shorten recovery periods due to supply chain disruptions. Supplier diversification, as well as supplier evaluation and selection, are discussed as risk aversion measures in many papers. However, even if the procurement source has been evaluated enough, there are problems, such as opportunity loss during recovery periods and soaring procurement costs during normal periods. In this chapter, to help Japanese manufacturers to alleviate opportunity loss under component procurement disruption situations and keep cost competitiveness in normal periods, decision-making models of supply chain structure assessment, supplier selection, procurement allocation, and trading contracts are designed and verified.
',book:{id:"11082",title:"Operations Management",coverURL:"https://cdn.intechopen.com/books/images_new/11082.jpg"},signatures:"Kotomichi Matsuno, Jiahua Weng, Noriyuki Hosokawa and Takahiro Ohno"},{id:"1085055",title:"Performance Measurement Using Deterministic and Stochastic Multiplicative Directional Distance Functions",slug:null,totalDownloads:3,totalDimensionsCites:0,doi:"10.5992/intechopen.1000179",abstract:'Performance measurement is essential for fostering continuous improvement of the production and operation management in a firm or organization. We consider a deterministic scenario based on a flexible structure of production technology and establish a multiplicative relationship between the generalized multiplicative directional distance function (GMDDF) and geometric distance function (GDF). We also introduce a stochastic multiplicative directional distance function (SMDDF). Based on a stochastic scenario, the SMDDF can be estimated by the method of convex nonparametric least squares. As an illustrative application, we investigate the productive performance of Japanese life insurance companies using a panel dataset spanning 2016 to 2020.
',book:{id:"11082",title:"Operations Management",coverURL:"https://cdn.intechopen.com/books/images_new/11082.jpg"},signatures:"Yu Zhao"},{id:"1085559",title:"Assessment of Medical Equipment Maintenance Management",slug:null,totalDownloads:2,totalDimensionsCites:0,doi:"10.5992/intechopen.1000210",abstract:'Today's modern hospital is highly dependent on different types of medical equipment to help diagnose, monitor, and treat patients. Medical equipment maintenance is important to reduce costs, reduce patient dissatisfaction, treat the patient in a timely manner, and reduce mortality and risks during patient care. Good maintenance management is important to have well-planned and implemented programs through which hospitals can minimize medical device failures or other problems with the operation of medical equipment. Medical equipment plays an important role in the hospital system; therefore, the acquisition, maintenance, and replacement of medical equipment are key factors in hospitals for the implementation of the health service. Thus, in order to ensure the quality of medical devices for the provision of medical care, it is imperative to evaluate the safety of using hospital maintenance management. In order to achieve these goals, hospitals must develop checklists that identify the state of performance of medical equipment maintenance. It is essential for clinical managers and engineers not only to increase the capacity of the hospital but also to predict the risks of sudden failure. Given the lack of unique and comprehensive maintenance management checklists, the current goal is to design and develop medical equipment maintenance management checklists.
',book:{id:"11082",title:"Operations Management",coverURL:"https://cdn.intechopen.com/books/images_new/11082.jpg"},signatures:"Călin Corciovă, Robert Fuior, Doru Andriţoi and Cătălina Luca"},{id:"81687",title:"Managing Foodservice Quality in the Foodservice Industry",slug:"managing-foodservice-quality-in-the-foodservice-industry",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.104800",abstract:"Quality has become a value that enables businesses to survive and continue existing. Henceforth, food industries need to entrench quality into their business performance. Foodservice quality is characterized as a service that bears on its ability to satisfy stated or implied needs and service free of defects. Foodservice businesses are an integral part of social life, both biologically and socially, biologically as satisfying the nutrition requirements of the society and socially in terms of addressing socialization and esthetics-pleasure values. Therefore, by adopting quality approaches, food industry businesses may encourage customers’ preferences for those businesses that diligently offer these services. Managing food service quality is a complex and challenging task requiring commitment, discipline, and emergent effort from everyone involved in food production processes. The task also requires the necessary management and administration techniques to continuously improve all processes (including quality control from raw material to finished product). Food industries need to be organizationally structured, establish policies and quality programs, measure customer satisfaction, use more quality tools and methodologies, embrace knowledge, apply techniques, and food safety programs to manage food quality. 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She is also Invisalign certified. She’s working as a Senior Lecturer in the Department of Orthodontics, SRM Dental College since November 2019. She is actively involved in teaching orthodontics to the undergraduates and the postgraduates. Her clinical research topics include new orthodontic brackets, fixed appliances and TADs. She’s published 4 articles in well renowned indexed journals and has a published patency of her own. Her private practice is currently limited to orthodontics and works as a consultant in various clinics.",institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"323731",title:"Prof.",name:"Deepak M.",middleName:"Macchindra",surname:"Vikhe",slug:"deepak-m.-vikhe",fullName:"Deepak M. Vikhe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/323731/images/13613_n.jpg",biography:"Dr Deepak M.Vikhe .\n\n\t\n\tDr Deepak M.Vikhe , completed his Masters & PhD in Prosthodontics from Rural Dental College, Loni securing third rank in the Pravara Institute of Medical Sciences Deemed University. He was awarded Dr.G.C.DAS Memorial Award for Research on Implants at 39th IPS conference Dubai (U A E).He has two patents under his name. He has received Dr.Saraswati medal award for best research for implant study in 2017.He has received Fully funded scholarship to Spain ,university of Santiago de Compostela. He has completed fellowship in Implantlogy from Noble Biocare. \nHe has attended various conferences and CDE programmes and has national publications to his credit. His field of interest is in Implant supported prosthesis. Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. 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Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Univeristy of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:null},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\nHer topics of interest are biomaterials science and cell culture studies. She has many articles in international and national scientific journals and chapters in books; she also has participated in several scientific projects supported by Istanbul University Research fund.",institutionString:null,institution:null},{id:"260116",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yaltirik",slug:"mehmet-yaltirik",fullName:"Mehmet Yaltirik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/260116/images/7413_n.jpg",biography:"Birth Date 25.09.1965\r\nBirth Place Adana- Turkey\r\nSex Male\r\nMarrial Status Bachelor\r\nDriving License Acquired\r\nMother Tongue Turkish\r\n\r\nAddress:\r\nWork:University of Istanbul,Faculty of Dentistry, Department of Oral Surgery and Oral Medicine 34093 Capa,Istanbul- TURKIYE",institutionString:null,institution:null},{id:"172009",title:"Dr.",name:"Fatma Deniz",middleName:null,surname:"Uzuner",slug:"fatma-deniz-uzuner",fullName:"Fatma Deniz Uzuner",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/172009/images/7122_n.jpg",biography:"Dr. Deniz Uzuner was born in 1969 in Kocaeli-TURKEY. After graduating from TED Ankara College in 1986, she attended the Hacettepe University, Faculty of Dentistry in Ankara. \nIn 1993 she attended the Gazi University, Faculty of Dentistry, Department of Orthodontics for her PhD education. After finishing the PhD education, she worked as orthodontist in Ankara Dental Hospital under the Turkish Government, Ministry of Health and in a special Orthodontic Clinic till 2011. Between 2011 and 2016, Dr. Deniz Uzuner worked as a specialist in the Department of Orthodontics, Faculty of Dentistry, Gazi University in Ankara/Turkey. In 2016, she was appointed associate professor. Dr. Deniz Uzuner has authored 23 Journal Papers, 3 Book Chapters and has had 39 oral/poster presentations. She is a member of the Turkish Orthodontic Society. Her knowledge of English is at an advanced level.",institutionString:null,institution:null},{id:"332914",title:"Dr.",name:"Muhammad Saad",middleName:null,surname:"Shaikh",slug:"muhammad-saad-shaikh",fullName:"Muhammad Saad Shaikh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jinnah Sindh Medical University",country:{name:"Pakistan"}}},{id:"315775",title:"Dr.",name:"Feng",middleName:null,surname:"Luo",slug:"feng-luo",fullName:"Feng Luo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Sichuan University",country:{name:"China"}}},{id:"423519",title:"Dr.",name:"Sizakele",middleName:null,surname:"Ngwenya",slug:"sizakele-ngwenya",fullName:"Sizakele Ngwenya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419270",title:"Dr.",name:"Ann",middleName:null,surname:"Chianchitlert",slug:"ann-chianchitlert",fullName:"Ann Chianchitlert",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419271",title:"Dr.",name:"Diane",middleName:null,surname:"Selvido",slug:"diane-selvido",fullName:"Diane Selvido",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419272",title:"Dr.",name:"Irin",middleName:null,surname:"Sirisoontorn",slug:"irin-sirisoontorn",fullName:"Irin Sirisoontorn",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"355660",title:"Dr.",name:"Anitha",middleName:null,surname:"Mani",slug:"anitha-mani",fullName:"Anitha Mani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"355612",title:"Dr.",name:"Janani",middleName:null,surname:"Karthikeyan",slug:"janani-karthikeyan",fullName:"Janani Karthikeyan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"334400",title:"Dr.",name:"Suvetha",middleName:null,surname:"Siva",slug:"suvetha-siva",fullName:"Suvetha Siva",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"334239",title:"Prof.",name:"Leung",middleName:null,surname:"Wai Keung",slug:"leung-wai-keung",fullName:"Leung Wai Keung",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Hong Kong",country:{name:"China"}}}]}},subseries:{item:{id:"4",type:"subseries",title:"Fungal Infectious Diseases",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment",scope:"Fungi are ubiquitous and there are almost no non-pathogenic fungi. Fungal infectious illness prevalence and prognosis are determined by the exposure between fungi and host, host immunological state, fungal virulence, and early and accurate diagnosis and treatment. \r\nPatients with both congenital and acquired immunodeficiency are more likely to be infected with opportunistic mycosis. Fungal infectious disease outbreaks are common during the post- disaster rebuilding era, which is characterised by high population density, migration, and poor health and medical conditions.\r\nSystemic or local fungal infection is mainly associated with the fungi directly inhaled or inoculated in the environment during the disaster. The most common fungal infection pathways are human to human (anthropophilic), animal to human (zoophilic), and environment to human (soilophile). Diseases are common as a result of widespread exposure to pathogenic fungus dispersed into the environment. \r\nFungi that are both common and emerging are intertwined. In Southeast Asia, for example, Talaromyces marneffei is an important pathogenic thermally dimorphic fungus that causes systemic mycosis. Widespread fungal infections with complicated and variable clinical manifestations, such as Candida auris infection resistant to several antifungal medicines, Covid-19 associated with Trichoderma, and terbinafine resistant dermatophytosis in India, are among the most serious disorders. \r\nInappropriate local or systemic use of glucocorticoids, as well as their immunosuppressive effects, may lead to changes in fungal infection spectrum and clinical characteristics. Hematogenous candidiasis is a worrisome issue that affects people all over the world, particularly ICU patients. CARD9 deficiency and fungal infection have been major issues in recent years. Invasive aspergillosis is associated with a significant death rate. Special attention should be given to endemic fungal infections, identification of important clinical fungal infections advanced in yeasts, filamentous fungal infections, skin mycobiome and fungal genomes, and immunity to fungal infections.\r\nIn addition, endemic fungal diseases or uncommon fungal infections caused by Mucor irregularis, dermatophytosis, Malassezia, cryptococcosis, chromoblastomycosis, coccidiosis, blastomycosis, histoplasmosis, sporotrichosis, and other fungi, should be monitored. \r\nThis topic includes the research progress on the etiology and pathogenesis of fungal infections, new methods of isolation and identification, rapid detection, drug sensitivity testing, new antifungal drugs, schemes and case series reports. It will provide significant opportunities and support for scientists, clinical doctors, mycologists, antifungal drug researchers, public health practitioners, and epidemiologists from all over the world to share new research, ideas and solutions to promote the development and progress of medical mycology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",hasOnlineFirst:!0,hasPublishedBooks:!1,annualVolume:11400,editor:{id:"174134",title:"Dr.",name:"Yuping",middleName:null,surname:"Ran",slug:"yuping-ran",fullName:"Yuping Ran",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9d6QAC/Profile_Picture_1630330675373",biography:"Dr. Yuping Ran, Professor, Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China. Completed the Course Medical Mycology, the Centraalbureau voor Schimmelcultures (CBS), Fungal Biodiversity Centre, Netherlands (2006). International Union of Microbiological Societies (IUMS) Fellow, and International Emerging Infectious Diseases (IEID) Fellow, Centers for Diseases Control and Prevention (CDC), Atlanta, USA. Diploma of Dermatological Scientist, Japanese Society for Investigative Dermatology. Ph.D. of Juntendo University, Japan. Bachelor’s and Master’s degree, Medicine, West China University of Medical Sciences. Chair of Sichuan Medical Association Dermatology Committee. General Secretary of The 19th Annual Meeting of Chinese Society of Dermatology and the Asia Pacific Society for Medical Mycology (2013). In charge of the Annual Medical Mycology Course over 20-years authorized by National Continue Medical Education Committee of China. Member of the board of directors of the Asia-Pacific Society for Medical Mycology (APSMM). Associate editor of Mycopathologia. Vice-chief of the editorial board of Chinses Journal of Mycology, China. Board Member and Chair of Mycology Group of Chinese Society of Dermatology.",institutionString:null,institution:{name:"Sichuan University",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null,series:{id:"6",title:"Infectious Diseases",doi:"10.5772/intechopen.71852",issn:"2631-6188"},editorialBoard:[{id:"302145",title:"Dr.",name:"Felix",middleName:null,surname:"Bongomin",slug:"felix-bongomin",fullName:"Felix Bongomin",profilePictureURL:"https://mts.intechopen.com/storage/users/302145/images/system/302145.jpg",institutionString:null,institution:{name:"Gulu University",institutionURL:null,country:{name:"Uganda"}}},{id:"45803",title:"Ph.D.",name:"Payam",middleName:null,surname:"Behzadi",slug:"payam-behzadi",fullName:"Payam Behzadi",profilePictureURL:"https://mts.intechopen.com/storage/users/45803/images/system/45803.jpg",institutionString:"Islamic Azad University, Tehran",institution:{name:"Islamic Azad University, Tehran",institutionURL:null,country:{name:"Iran"}}}]},onlineFirstChapters:{paginationCount:14,paginationItems:[{id:"82103",title:"The Role of Endoplasmic Reticulum Stress and Its Regulation in the Progression of Neurological and Infectious Diseases",doi:"10.5772/intechopen.105543",signatures:"Mary Dover, Michael Kishek, Miranda Eddins, Naneeta Desar, Ketema Paul and Milan Fiala",slug:"the-role-of-endoplasmic-reticulum-stress-and-its-regulation-in-the-progression-of-neurological-and-i",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"80954",title:"Ion Channels and Neurodegenerative Disease Aging Related",doi:"10.5772/intechopen.103074",signatures:"Marika Cordaro, Salvatore Cuzzocrea and Rosanna Di Paola",slug:"ion-channels-and-neurodegenerative-disease-aging-related",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Ion Channels - From Basic Properties to Medical Treatment",coverURL:"https://cdn.intechopen.com/books/images_new/10838.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"81647",title:"Diabetes and Epigenetics",doi:"10.5772/intechopen.104653",signatures:"Rasha A. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. 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