Effects from Earthquakes [8]
\r\n\tFurther development of geophysical methods in the direction of constructing more and more adequate models of media and phenomena necessarily leads to more and more complex problems of mathematical geophysics, for which not only inverse, but also direct problems become significantly incorrect. In this regard, it is necessary to develop a new concept of regularization for simultaneously solving a system of heterogeneous operator equations.
\r\n\r\n\tCurrently, the study of processes associated not only with geophysics and astrophysics but also with biology and medicine requires even more complication of interpretation models from non-linear and heterogeneous to hierarchical. This book will be devoted to the creation of new mathematical theories for solving ill-posed problems for complicated models.
",isbn:"978-1-83962-592-3",printIsbn:"978-1-83962-591-6",pdfIsbn:"978-1-83962-593-0",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,hash:"d93195bb64405dd9e917801649f991b3",bookSignature:"Prof. Olga Alexandrovna Hachay",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/8253.jpg",keywords:"Ill-Posed, Inverse Problems, Geophysics, Seismic, Electromagnetic, Thermal, Magnetic, Medicine, \r\nMathematical, Algorithms, Hierarchical, Nonlinear, Historical Description, Regularization",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 7th 2019",dateEndSecondStepPublish:"October 28th 2019",dateEndThirdStepPublish:"December 27th 2019",dateEndFourthStepPublish:"March 16th 2020",dateEndFifthStepPublish:"May 15th 2020",remainingDaysToSecondStep:"a month",secondStepPassed:!0,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,editors:[{id:"150801",title:"Prof.",name:"Olga",middleName:"Alexandrovna",surname:"Hachay",slug:"olga-hachay",fullName:"Olga Hachay",profilePictureURL:"https://mts.intechopen.com/storage/users/150801/images/system/150801.jpg",biography:"EDUCATION BACKGROUND:\r\nAstrophysics (1969) Ural State University \r\nPh. D. «The inverse problem for electromagnetic research of one-dimensional medium » (1979) IZMIRAN, Russian Academy of Sciences, Moscow\r\nProf: «Mathematical modeling and interpretation alternating electromagnetic fields in the heterogeneous crust and earth’s Mantle » (1994) Moscow State University Geological Faculty.\r\nLanguage: Fluent in Russian, English, German. \r\nEMPLOYMENT: HISTORY\r\nFrom 1969 scientific member of the Institute of Geophysics UB RAS\r\n1995-2004 Chief of the group of seismic and electromagnetic research. Elaboration of new common methods for searching the structure and the state of the upper crust Elaboration new theory of interpretation of electromagnetic and seismic fields and realizing it in new programs. From 2002-main scientific researcher of the Institute of geophysics UB RAS From 2008 –leader scientific researcher of the Institute in the frame of the laboratory of borehole geophysics.",institutionString:"Ural Branch of the Russian Academy of Sciences",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Ural Branch of the Russian Academy of Sciences",institutionURL:null,country:{name:"Russia"}}}],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:"305835",firstName:"Ketrin",lastName:"Polesak",middleName:null,title:"Mrs.",imageUrl:"https://mts.intechopen.com/storage/users/305835/images/9351_n.png",email:"ketrin@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. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],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:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],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:"4816",title:"Face Recognition",subtitle:null,isOpenForSubmission:!1,hash:"146063b5359146b7718ea86bad47c8eb",slug:"face_recognition",bookSignature:"Kresimir Delac and Mislav Grgic",coverURL:"https://cdn.intechopen.com/books/images_new/4816.jpg",editedByType:"Edited by",editors:[{id:"528",title:"Dr.",name:"Kresimir",surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac"}],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:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3794",title:"Swarm Intelligence",subtitle:"Focus on Ant and Particle Swarm Optimization",isOpenForSubmission:!1,hash:"5332a71035a274ecbf1c308df633a8ed",slug:"swarm_intelligence_focus_on_ant_and_particle_swarm_optimization",bookSignature:"Felix T.S. Chan and Manoj Kumar Tiwari",coverURL:"https://cdn.intechopen.com/books/images_new/3794.jpg",editedByType:"Edited by",editors:[{id:"252210",title:"Dr.",name:"Felix",surname:"Chan",slug:"felix-chan",fullName:"Felix Chan"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3621",title:"Silver Nanoparticles",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"silver-nanoparticles",bookSignature:"David Pozo Perez",coverURL:"https://cdn.intechopen.com/books/images_new/3621.jpg",editedByType:"Edited by",editors:[{id:"6667",title:"Dr.",name:"David",surname:"Pozo",slug:"david-pozo",fullName:"David Pozo"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. 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"}}]},chapter:{item:{type:"chapter",id:"38202",title:"Seismic Risk of Structures and the Economic Issues of Earthquakes",doi:"10.5772/50789",slug:"seismic-risk-of-structures-and-the-economic-issues-of-earthquakes",body:'As one of the most devastating natural events, earthquakes impose economic challenges on communities and governments. The number of human and economic assets at risk is growing as megacities and urban areas develop all over the world. This increasing risk has been plotted in the damage and loss reports after the great earthquakes.
The 1975 Tangshan (China) earthquake killed about 200,000 people. The 1994 Northridge, (USA) earthquake left 57 dead and about 8,700 injured. The country experienced around $42 billion in losses due to it. The 1995 earthquake in Kobe (Japan) caused about 6,000 fatalities and over $120 Billion in economic loss. The August 1996 Izmit (Turkey) earthquake killed 20,000 people and caused $12 billion in economic loss. The 1999 Chi-chi (Taiwan) earthquake caused an estimated $8 billion in loss. The 2006 Gujarat (India) earthquake saw around 18,000 fatalities and 330,000 demolished buildings [1]. The Sichuan (China) earthquake, on May 12th 2008 left 88,000 people dead or missing and nearly 400,000 injured. That earthquake damaged or destroyed millions of homes, leaving five million homeless. It also caused extensive damage to basic infrastructure, including schools, hospitals, roads and water systems. The event cost around $29 billion in direct loss alone [2]. The devastating earthquake of March 2011 with its resulting tsunami along the east coast of Japan is known to be the world\'s most costly earthquake. The World Bank estimated the cost at $235 billion while government estimates reported the number at $305 billion. The event left 8,700 dead and more than 13,000 missing [3].
As has been shown, earthquake events have not only inflicted human and physical damage, they have also been able to cause considerable economic conflict in vulnerable cities and regions. The importance of the economic issues and the consequences of earthquakes attracted the attention of engineers and provided new research and working opportunities for engineers, who up until then had been concerned only with risk reduction options through engineering strategies [4].
Seismic loss estimation is an expertise provided by earthquake engineering and the manner in which it can be employed in the processes of assessing seismic loss and managing the financial and economical risk associated with earthquakes through more beneficial retrofit methods will be discussed. The methodology provides a useful tool for comparing different engineering alternatives from a seismic-risk-point of view based on a Performance Based Earthquake Engineering (PBEE) framework [5]. Next, an outline of the regional economic models employed for the assessment of earthquakes’ impact on economies will be briefly introduced.
The economic consequences of earthquakes may occur both before and after the seismic event itself [6]. However, the focus of this chapter will be on those which occur after earthquakes. The consequences and effects of earthquakes may be classified in terms of their primary or direct effects and their secondary or indirect effects. The indirect effects are sometimes referred to by economists as higher-order effects. The primary (direct) effects of an earthquake appear immediately after it as social and physical damage. The secondary (indirect) effects take into account the system-wide impact of flow losses through inter-industry relationships and economic sectors. For example, where damage occurs to a bridge then its inability to serve to passing vehicles is considered a primary or direct loss, while if the flow of the row material to a manufacturing plant in another area is interrupted due to the inability of passing traffic to cross the bridge, the loss due to the business’s interruption in this plant is called secondary or indirect loss. A higher-order effect is another term as an alternative to indirect or secondary effects which has been proposed by economists [7]. These potential effects of earthquakes may be categorized as: "social or human", "physical" and "economic" effects. This is summarized in Table 1 [8].
The term ‘total impact’ accordingly refers to the summation of direct (first-order effects) and indirect losses (higher-order effects). Various economic frameworks have been introduced to assess the higher-order effects of an earthquake.
With a three-sector hypothesis of an economy, it may be demonstrated in terms of a breakdown as three sectors: the primary sector as raw materials, the secondary sector as manufacturing and the tertiary sector as services. The interaction of these sectors after suffering seismic loss and the relative effects on each other requires study through proper economic models.
The PBEE process can be expressed in terms of a four-step analysis, including [9-10]:
Hazard analysis, which results in Intensity Measures (IMs) for the facility under study,
Structural analysis, which gives the Engineering Demand Parameters (EDPs) required for damage analysis,
Damage analysis, which compares the EDPs with the Damage Measure in order to decide for the failure of the facility, and;
Loss Analysis, which evaluates the occurrence of Decision Variables (DVs) due to failures.
Social or human effects | Physical effects | Economic effects | |
Primary effects (Direct or first-order) | Fatalities Injuries Loss of income or employment opportunities Homelessness | Ground deformation and loss of ground quality Collapse and structural damage to buildings and infrastructure Non-structural damage to buildings and infrastructure (e.g., component damage) | Disruption of business due to damage to industrial plants and equipment Loss of productive work force, through fatalities, injuries and relief efforts Disruption of communications networks Cost of response and relief |
Secondary effects (indirect or higher-order) | Disease or permanent disability Psychological impact of injury, Bereavement, shock Loss of social cohesion due to disruption of community Political unrest when government response is perceived as inadequate | Reduction of the seismic capacity of damaged structure which are not repaired Progressive deterioration of damaged buildings and infrastructure which are not repaired | Losses borne by the insurance industry, weakening the insurance market and increasing the premiums Losses of markets and trade opportunities, |
Effects from Earthquakes [8]
Considering the results of each step as a conditional event following the previous step and all of the parameters as independent random parameters, the process can be expressed in terms of a triple integral, as shown below, which is an application of the total probability theorem [11]:
The performance of a structural system or lifeline is described by comparing demand and capacity parameters. In earthquake engineering, the excitation, demand and capacity parameters are random variables. Therefore, probabilistic techniques are required in order to estimate the response of the system and provide information about the availability or failure of the facility after loading. The concept is included in the reliability design approach, which is usually employed for this purpose.
The reliability of a structural system or lifeline may be referred to as the ability of the system or its components to perform their required functions under stated conditions for a specified period of time. Because of uncertainties in loading and capacity, the subject usually includes probabilistic methods and is often made through indices such as a safety index or the probability of the failure of the structure or lifeline.
To evaluate the seismic performance of the structures, performance functions are defined. Let us assume that z=g(x1, x2, …,xn) is taken as a performance function. As such, failure or damage occurs when z<0. The probability of failure, pf, is expressed as follows:
Pf=P[z<0]
Simply assume that z=EDP-C where EDP stands for Engineering Demand Parameter and C is the seismic capacity of the structure.
Damage or failure in a structural system or lifeline occurs when the Engineering Demand Parameter exceeds the capacity provided. For example, in a bridge structural damage may refer to the unseating of the deck, the development of a plastic hinge at the bottom of piers or damage due to the pounding of the decks to the abutments, etc.
Given that EDP and C are random parameters having the expected or mean values of µEDP and µC and standard deviation of σEDP and σC, the “safety index” or “reliability index”, β, is defined as:
It has been observed that the random variables such as "EDP" or "C" follow normal or log-normal distribution. Accordingly, the performance function, z, also will follow the same distribution. Accordingly, probability of failure (or damage occurrence) may be expressed as a function of safety index, as follows:
Pf=φ (- β)=1- φ (β)
where φ( ) is a log-normal distribution function.
The Engineering Demand Parameters describe the response of the structural framing and the non-structural components and contents resulting from earthquake shaking. The parameters are calculated by structural response simulations using the IMs and corresponding earthquake motions. The ground motions should capture the important characteristics of earthquake ground motion which affect the response of the structural framing and non-structural components and building contents. During the loss and risk estimation studies, the EDP with a greater correlation with damage and loss variables must be employed.
The EDPs were categorized in the ATC 58 task report as either direct or processed [9]. Direct EDPs are those calculated directly by analysis or simulation and contribute to the risk assessment through the calculation of P[EDP | IM]; examples of direct EDPs include interstory drift and beam plastic rotation. Processed EDPs - for example, a damage index - are derived from the values of direct EDPs and data on component or system capacities. Processed EDPs could be considered as either EDPs or as Damage Measures (DMs) and, as such, could contribute to risk assessment through P[DM | EDP]. Direct EDPs are usually introduced in codes and design regulations. For example, the 2000 NEHRP Recommended Provisions for Seismic Regulations for Buildings and Other Structures introduces the EDPs presented in Table 2 for the seismic design of reinforced concrete moment frames [12-13]:
Reinforced concrete moment frames |
Axial force, bending moment and shear force in columns |
Bending moment and shear force in beams |
Shear force in beam-column joints |
Shear force and bending moments in slabs |
Bearing and lateral pressures beneath foundations |
Interstory drift (and interstory drift angle) |
EDPs required for the seismic design of reinforced concrete moment frames by [12-13]
Processed EDPs are efficient parameters which could serve as a damage index during loss and risk estimation for structural systems and facilities. A Damage Index (DI), as a single-valued damage characteristic, can be considered to be a processed EDP [10]. Traditionally, DIs have been used to express performance in terms of a value between 0 (no damage) and 1 (collapse or an ultimate state). An extension of this approach is the damage spectrum, which takes on values between 0 (no damage) and 1 (collapse) as a function of a period. A detailed summary of the available DIs is available in [14].
Park and Angin [15] developed one of the most widely-known damage indices. The index is a linear combination of structural displacement and hysteretic energy, as shown in the equation:
where umax and uc are maximum and capacity displacement of the structure, respectively, Eh is the hysteresis energy, Fy is the yielding force and β is a constant.
See Powell and Allahabadi, Fajfar, Mehanny and Deierlein, as well as Bozorgnia and Bertero for more information about other DIs in [16-19].
The seismic fragility of a structure refers to the probability that the Engineering Demand Parameter (EDP) will exceed seismic capacity (C) upon the condition of the occurrence of a specific Intensity Measure (IM). In other words, seismic fragility is probability of failure, Pf, on the condition of the occurrence of a specific intensity measure, as shown below:
Fragility=P [EDP>C|IM]
In a fragility curve, the horizontal axis introduces the IM and the vertical axis corresponds to the probability of failure, Pf. This curve demonstrates how the variation of intensity measure affects the probability of failure of the structure.
Statistical approach, analytical and numerical simulations, and the use of expert opinion provide methods for developing fragility curves.
With a statistical approach, a sufficient amount of real damage-intensity data after earthquakes is employed to generate the seismic fragility data. As an example, Figure 1 demonstrates the empirical fragility curves for a concrete moment resisting frame, according to the data collected after Northridge earthquake [20].
Empirical fragility curves for a concrete moment resisting frame building class according to the data collected after the Northridge Earthquake, [20].
With an analytical approach, a numerical model of the structure is usually analysed by nonlinear dynamic analysis methods in order to calculate the EDPs and compare the results with the capacity to decide about the failure of the structure. The works in [21-24] are examples of analytical fragility curves for highway bridge structures by Hwang et al. 2001, Choi et al. 2004, Padgett et al., 2008, and Padgett et al 2008.
Figure 2 demonstrates the steps for computing seismic fragility in analytical approach.
Procedure for generating analytical fragility curves
To overcome the uncertainties in input excitation or the developed model, usually adequate number of records and several numerical models are required so that the dispersion of the calculated data will be limited and acceptable. This is usually elaborating and increases the cost of the generation of fragility data in this approach. Probabilistic demand models are usually one of the outputs of nonlinear dynamic analysis. Probabilistic demand models establish a relationship between the intensity measure and the engineering demand parameter. Bazorro and Cornell proposed the model given below [25]:
where
Assuming a log-normal distribution for fragility values, they are then estimated using the following equation:
The parameter β introduces the dispersion in the resulting data from any calculations. An example of analytical fragility curves for highway bridges is shown in Figure 3.
Fragility curve for the 602-11 bridge for 4 damage states [21]
Given a lack of sufficient statistical or analytical data, expert opinion provides a valuable source for estimating the probability of the failure of typical or specific buildings for a range of seismic intensity values. The number of experts, their proficiency and the quality of questionnaires, including the questions, their adequacy and coverage, can affect the uncertainty of the approach and its results.
The expected risk of a project, assuming that the intensity measure as the seismic hazard parameter is deterministic, is calculated by equation 10, below:
R=PL
where P is the probability of the occurrence of damage and L indicates the corresponding loss. The equation shows that any factor which alters either the probability or the value of the resulted loss affects the related risk. Diverse damage modes and associated loss values, Li (i=1 to a number of probable damage modes), with a different probability of occurrence, Pi, may be envisaged for a structure. The probable risk of the system, R, can be estimated as a summation of the loss of each damage mode:
R=∑PiLi
Loss functions are usually defined as the replacement cost - corresponding to each damage state - versus seismic intensity. The loss associated with each damage mode, presented schematically in Figure 4, is usually collected through questionnaires, statistical data from post-earthquake observations or else calculated through numerical simulations. ATC 13 provides an example of the collection of earthquakes’ structural and human damage and loss data for California [26].
Seismic loss data
A summary of calculations required for estimating the risk of a project under a specific seismic intensity level may be illustrated by an "event tree" diagram.
An Event tree diagram is a useful tool for estimation of the probability of occurrence of damage and corresponding loss in a specific project due to a certain seismic event. The procedure requires information about seismic intensity, probable damage modes, seismic fragility values and the vulnerability and loss function of the facility under study.
As an example, suppose that partial seismic damage, structural collapse, partial fire and extended fire are considered to be the loss-generating consequents of an earthquake for a building. Figures 5 and 6 are the event tree diagrams, which demonstrate the procedure followed to calculate the corresponding risk for the seismic intensity of two levels of PGA=300gal and 500gal. To select the probability of the occurrence of each damage mode, (i.e., the probability of the exceedance of damage states) the fragility curves can be utilized. Each node is allocated to a damage mode. The probability of the incidence or non-incidence of each damage mode is mentioned respectively on the vertical or horizontal branch immediately after each node. The probability of the coincidence of the events at the same root is calculated by multiplying the probability of incidence of the events on the same root. The final total risk, R, is then calculated as the summation of all Ris.
Figure 7.a demonstrates the distribution of risk values for different damage modes. In addition, it can be seen how increasing seismic intensity increased the risk of the project. Figure 7.b shows the distribution of the probability of the occurrence of different loss values and how an increase of seismic intensity from 300gal to 500gal affects it in this structure. As mentioned, the calculations in an event tree diagram are performed for a special level of hazard. The curves present valuable probabilistic data about the points on the seismic loss curve. A seismic loss curve may be developed according to the information from event trees for a range of probable seismic intensities of the site. Figure 8 shows a schematic curve for the seismic loss of a project. The curve is generated by integrating the seismic risk values for each damage mode. It provides helpful data for understanding the contents and elements of the probable loss for each level of earthquake hazard.
ND: No Damage, F: Partial Fire, CF: Complete Fire, PD: Partial Damage, CO: Collapse Event Tree, PGA=300gal
Event Tree, PGA=500gal
The information provided by an event tree simply increases the awareness of engineers and stakeholders about the importance and influence of each damage mode on the seismic risk of the project and demonstrates the distribution of probable loss among them.
a) Distribution of seismic risk values vs. damage, b) Probability of occurrence vs. probable loss
Seismic loss curve
The total probable loss calculated by event trees provides valuable information for estimating the annual probable loss of facilities, as shown in the next part.
If the uncertainties in the seismic hazard assessment of a specific site could be avoided, a deterministic approach could provide an easy and rational method for this purpose. However, the nature of a seismic event is such that it usually involves various uncertainty sources, such as the location of the source, the faulting mechanism and the magnitude of the event, etc. The probabilistic seismic hazard analysis offers a useful tool for the assessment of annual norms of seismic loss and risk. [27]
In an active area source, k, with a similar seismicity all across it, the seismicity data gives the maximum magnitude of muk and a minimum of mlk and the frequency of the occurrence of vk. Similar assumptions can be extended for a line source from which the Probability Density Function (PDF) of magnitude for a site, fMk(mk), can be constructed, as is schematically demonstrated by Figure 9.a [27].
Variability of seismic intensity as a function of magnitude and distance
if in the active zone under study, an area or line source can be assumed as a point, the probability density function of the focal distance of the site, x, fXk (xk) can be developed, as schematically demonstrated in Figure 9.b.
Ground motion prediction models - or attenuation functions - include the gradual degradation of seismic energy passing through a medium of ground up to site. The ground motion prediction models, schematically shown in Figure 10, have been provided according to the statistical data, characteristics of the ground, seismic intensity and distance, etc.
a) Schematic ground motion prediction models for a site
The ground motion prediction models are usually empirical relations, which do not match the real data exactly. The dispersion between the real data and the empirical attenuation relations may be modelled by a probability density function f(am, x) which shows the distribution density function of intensity a if a seismic event with a magnitude of m occurs at a distance x from the site. Figure 11 shows how f(am, x) changes when an intensity measure a varies.
Probability of exceedance from a specific intensity using a probability density function
According to the above-mentioned collected data, the annual rate of earthquakes with an intensity (acceleration) larger than a, v(a) can be calculated from the following equation:
Where, PA(amk, xu) stands for the probability of occurrence of an earthquake with an intensity larger than a at a site with an attenuation relation of fA(am,x).
Poison process is usually employed to model the rate of the occurrence of earthquakes within specific duration. For an earthquake with an annual probability of occurrence of (a), the probability of the occurrence of n earthquakes of intensity greater than a within t years is given by:
Meanwhile, the annual probability of exceedance from the intensity a, P(a) can be expressed as:
The time interval of earthquakes with an intensity exceeding a is called the return period and is shown as Ta. The parameter can be calculated first knowing that the probability of T is longer than t:
then the probability distribution function of Ta becomes:
Accordingly, the probability density function of T, fT, is derived by taking a derivation of the above FT function:
The return period is known as the mean value of T and can be calculated as:
The probability density function, fA(a), the accumulative probability, FA(a), and the annual probability of exceedance function, P(a), for intensity a (for example PGA), are related to each other, as shown below:
A hazard curve, as shown below, refers to a curve which relates the annual probability of exceedance of an intensity a, P(a), to the intensity value a. Two seismic hazard curves were employed in Figure 12 to schematically demonstrate two sites with relatively low and high seismic hazard.
Seismic hazard curve. A demonstration of relatively low and high seismic hazard by means of seismic hazard curves
A probabilistic hazard analysis for a site has resulted in the following plots of a probability density function and accumulative distribution.
Seismic hazard data, a) PDF of intensity, b) cumulative probability of occurrence∫-∞afA(a)da, and c) annual probability of exceedance, where the seismic hazard curve = ∫a+∞fA(a)da
By applying the data available from seismic hazard and loss curves, an annual seismic risk density and seismic risk curve can be estimated.
A seismic loss curve is a useful tool for comparing the seismic capacity of different facilities. Seismic hazard and loss curves with basic information about the site and facility play a key role in the evaluation of seismic risk assessment and management procedures. The "annual seismic risk density" and "seismic risk" curves constitute two important measures which can be derived from the above data. The steps to obtain annual seismic risk density curves are shown in Figure 14. The probability density function for seismic intensity (e.g., PGA) is found using a seismic hazard curve using equations 18-20. Accordingly, the annual seismic risk density is derived by multiplying this result with the corresponding loss values, as shown in Figure 14.d below [27].
Generating the annual seismic risk density from seismic hazard and loss curves, a) seismic hazard curve, b) probability density function, c) seismic loss curve and d) annual seismic risk density.
Seismic risk curve
The seismic risk curve, as shown in Figure 15, is calculated using seismic hazard probability and loss values corresponding to similar intensities.
The seismic risk and annual risk density contain helpful information for risk management efforts. As an example, insurance premiums are calculated using this data for various seismic loss limits which can be decided by the client and insurance company.
Perhaps the most widely used modelling framework is the Input-Output model. The method has been extensively discussed in the literature (for example, in [28-30]). The method is a linear model, which includes purchase and sales between sectors of an economy based on technical relations of production. The method specially focuses on the production interdependencies among the elements and, therefore, is applicable for efficiently exploring how damage in a party or sector may affect the output of the others. HAZUS has employed the model in its indirect loss estimation module [31].
Computable General Equilibrium (CGE) offers a multi-market simulation model based on the simultaneous optimization of behaviour of individual consumers and firms in response to price signals, subject to economic account balances and resource constraints. The nonlinear approach retains many of the advantages of the linear I-O methods and overcomes most of its disadvantages [32].
As the third alternative, econometric models are statistically estimated as simultaneous equation representations of the aggregate workings of an economy. A huge data collection is required for the model and the computation process is usually costly [33].
As another approach, Social Accounting Matrices (SAMs) have been utilized to examine the higher-order effects across different socio-economic agents, activities and factors. Cole, in [34-36], studied the subject using one of the variants of SAM. The SAM approach, like I-O models, has rigid coefficients and tends to provide upper bounds for estimates. On the other hand, the framework can derive the distributional impacts of a disaster in order to evaluate equity considerations for public policies against disasters. A summary of the advantages and disadvantages of the models mentioned has been presented in Table 3 [37].
The economic consequences of earthquakes due to the intensity of the event and the characteristics of the affected structures may be influential on a large-scale economy. As an example, the loss flowing from the March 2011 earthquake and tsunami in east Japan could amount to as much as $235 billion and the effects of the disaster will be felt in economies across East Asia [3]. To study how the damage to an economic sector of society may ripple into other sectors, regional economic models are employed. Several spatial economic models have been applied to study the impacts of disasters. Okuyama and Chang, in [30], summarized the experiences about the applications of the three main models - namely Input-Output, Social Accounting and Compatible General Equilibrium - to handle the impact of disaster on socio-economic systems, and comprehensively portrayed both their merits and drawbacks. However, they are based on a number of assumptions that are questionable in, for example, seismic catastrophes.
Studies have been recommended to address issues such as double-counting, the response of households and the evaluation of financial situations. According to the National Research Council, \'the core of the problem with the statistically based regional models is that the historical relationship, embodied in these models, is likely to be disrupted in a natural disaster. In short, regional economic models have been developed over time primarily to forecast future economic conditions or to estimate the effects of a permanent change (e.g., the opening or closing of a manufacturing plant). The random nature and abruptness of a natural disaster do not fit the event pattern upon which regional economic models are based [38].
Strengths | Weaknesses | |
IO | - simple structure - detailed inter-industry linkages - wide range of analytical techniques available - easily modified and integrated with other models | - linear structure - rigid coefficients - no supply capacity constraint - no response to price change - overestimation of impact |
SAM | - more detailed interdependency among activities, factors and institutions - wide range of analytical techniques available - used widely for development studies | - linear structure - rigid coefficients - no supply capacity constraint - no response to price change - data requirement - overestimation of impact |
CGE | - non-linear structure - able to respond to price change - able to cooperate with substitution - able to handle supply capacity constraints | - too flexible to handle changes - data requirement and calibration - optimization behaviour under disaster -underestimation of impact |
Econometrics | - statistically rigorous - stochastic estimate - able to forecast over time | - data requirement (time series and cross section) - total impact rather than direct and higher-order - order of impacts distinguished |
The advantages and disadvantages of the regional economic models for a seismic impact assessment [37]
Yamano et al., in [39], examined the economic impacts of natural disasters using the originally estimated finer geographical scale production datasets and the redefined interregional input–output table. For more effective estimates of the direct losses of the disasters, the precise geographical information of industrial distribution was required because most of the economic data was published according to political boundaries, which may be too aggregated to provide practical information for disaster preventions and retrofit policies. The direct losses were captured by the output data at the district level (500square meters) by sector and population density. The map of economic hotspots was obtained after estimating the economic importance of each district. They showed that the advantages of finer geographical scale datasets and the total economic losses are not proportional to the distributions of the population and industrial activities. In other words, the disaster prevention and retrofit policies have to consider the higher-order effects in order to reduce the total economic loss [39].
It has been shown that in having both virtues and limitations, these alternate I-O, CGE or econometric frameworks may be chosen according to various considerations, such as data collection/compilation, the expected output, research objectives and costs. Major impediments to analysing a disaster’s impact may involve issues related to data collection and estimation methodologies, the complex nature of a disaster’s impact, an inadequate national capacity to undertake impact assessments and the high frequency of natural disasters.
In this chapter, a summary of the methodology for performance-based earthquake engineering and its application in seismic loss estimation was reviewed. Describing the primary and secondary effects of earthquakes, it was mentioned that the loss estimation process for the direct loss estimation of structures consists of four steps, including hazard analysis, structural dynamics analysis, damage analysis and seismic loss analysis. EDPs, as the products of structural dynamic analysis, were explained and the methodologies’ seismic fragility curves were briefly introduced. Employing a probabilistic hazard analysis, the method for deriving the annual probability of seismic risk exceedance and seismic risk curves was presented. Considering the importance of both secondary effects and interactions between different sectors of an economy due to seismic loss, those regional economic models with common application in the evaluation of economic conditions after natural disasters (e.g., earthquakes) were mentioned.
Osteoarthritis (OA) is a common disease that can affect joints from any part of the body, and it represents a major cause of disability and joint pain worldwide [1, 2]. OA most commonly affects the knee, hip, and shoulder, and it was estimated that more than 25 million people in the USA were affected by some form of OA in the last decade [3]. In addition, OA presents a high susceptibility to affect female gender, elderly people, and obese individuals [4].
The progression of OA leads to cartilage degradation with subchondral bone remodeling, hypertrophy of the joint capsule, and osteophytes formation, causing pain [1, 5, 6]. Although the development of OA is considered a heterogeneous process, which comprises a number of genetic and environmental causes, the presence of local causes, such as trauma and hypermobility of the joint, may worsen OA [2, 7].
The accurate identification of osteoarthritic features has been studied in order to radiographically grade the stages of OA. The Kellgren-Lawrence classification is the most widely used, especially in clinical researches. This classification evaluates the appearance of osteophytes and cysts, joint space loss, and sclerosis, and it grades the severity from 0 to 5 points. The radiological features found in OA joints were graded as follows: (1) formation of osteophytes on joint margins or on tibia spines for knee OA; (2) periarticular ossicles in relation to distal and proximal interphalangeal joints; (3) narrowing of joint cartilage and sclerosis of subchondral bone; (4) pseudocystic areas with sclerotic walls in the subchondral bone; and (5) altered shape of the bone ends [8]. Some of these criteria were adopted by the World Health Organization (WHO) as the standard for studies on OA.
Current options for the treatment of OA focus on reducing pain (non-steroidal anti-inflammatory drugs—NSAIDs) and joint viscosupplementation (intra-articular injections of hyaluronic acid) [1]. Besides presenting a short-term effect, the chronic use of some of these medications, especially NSAIDs, may cause serious adverse events, including toxicity and risk of thromboembolism [9, 10]. In severe cases, surgical procedures, mostly joint replacement, are suggested [1]. Novel alternative therapies, called orthobiologics, have emerged from the need of tissue regeneration. Clinical trials using orthobiologics, which comprise platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), fat graft (Biofat), and expanded mesenchymal stem cells, have shown promising results for the treatments of OA from any origin [11, 12, 13, 14].
Moreover, monoclonal antibody (mAb) therapy represents one of the alternative treatments that aim to control inflammation and slow structural progression [15]. This approach focuses on blocking specific molecules responsible for the maintenance of OA. Preclinical studies with ADAMTS mAbs reported a significant decrease in histological scores after 3 months of treatment [16]. Adalimumab is an anti-TNF-α therapy used in diverse immune-mediated diseases, and it presents a protective role for OA as it reduces the severity of the cartilage lesion and improves the structure of subchondral bone [17]. Since IL-1 family may induces the production of metalloproteinases (MMP), it has also become a target for mAb therapy, and, in a randomized controlled trial with patients who presented knee OA, it was reported great improvement on pain relief [18].
In addition to macroscopic features, several cellular and molecular alterations are present in OA, such as catabolism and anabolism events; hypertrophy and, consequently, death of chondrocytes; and impaired autophagy process [19]. Also, a chronic low-grade inflammation interplayed with immune system has been considered to present a crucial role in the maintenance of OA [1]. This fact is supported by recent progress, which has considerably improved the knowledge regarding factors involved in the OA development and the mechanisms responsible for its progression.
The inflammation observed in OA is believed to involve innate immune response prior to a mild degree of adaptive immunity [20]. During tissue damage, a group of endogenous molecules, called damage-associated molecular pattern (DAMP), signals the immune cells to induce a protective response against the tissue, causing tissue repair. However, a prolonged signaling of DAMP to immune cells leads to an exacerbated cytokine release, which can be destructive to the tissue [21, 22].
Innate immune cells activated by DAMP include macrophages and mast cells, which have shown to present (displayed or demonstrated) a key role in the pathogenesis of OA. Mast cells are considered regulators of vascular permeability, and they may play a crucial role in OA joint inflammation as they facilitate leukocyte infiltration [23].
Macrophages exhibit a functional plasticity based on the environment in which they are located or present [22]. However, their chronic activation can lead to the production of proinflammatory cytokines, which worsen the osteoarthritic joints [24]. In vitro studies of human OA synovium-derived cells showed that macrophage depletion results in diminishing of inflammatory response by decrease of proteolytic enzyme expression, such as metalloproteinases (MMP) This fact is supported by in vitro studies with cell culture suspension of human OA synovium, which reported that, after macrophage depletion, there was a decrease in the production of inflammatory response by less activity of proteolytic enzymes, such as metalloproteinases (MMP) [25]. Although macrophages may also present a protective role, as they are known to secrete transforming growth factor β (TGF-β), which would enhance cartilage repair, intra-articular injection of TGF-β in mice knee led to osteophyte formation and fibrosis [26].
In addition, natural killer (NK) infiltrates are commonly found in synovial tissue from patients who underwent joint replacement surgeries, and a subset of NK cells (CD56bright) was found to be greatly expanded in patients with inflammatory arthritis who have not undergone joint replacement surgeries. However, the effect of these cells on the development of OA has not been elucidated yet [27, 28, 29]. NK cells secrete protease enzymes called granzyme type A and B, which correlate to cytolytic potency. Granzymes can be released during degranulation of cytotoxic cells and, when delivered intracellularly to the target cells, they induce apoptosis. Granzyme A also stimulates the production of tumor necrosis factor (TNF-α), IL-6, and IL-8, while granzyme B may intensify the degradation of extracellular matrix [30, 31]. Tak et al. identified both types of granzymes in synovia from OA and rheumatoid arthritis. However, another study later showed that NK cells within OA synovia were granzyme negative with potential to produce the interferon-γ (IFN-γ) when expanded with IL-2 and stimulated with cytokines known to trigger IFN-γ production in blood NK cells, such as IL-12 and IL-18 [27, 32].
The presence of IFN-γ has a role in the bone resorption and consequently in the osteoclastogenesis process, but the studies have shown controversial results in this regard: in vitro evidence reported that IFN-γ, via TRANCE pathway, strongly suppresses osteoclastogenesis in culture of mononuclear phagocyte cells, which are the osteoclast precursors [33], whereas in culture of peripheral blood it may enhance osteoclast production as IFN-γ increases superoxide generation by neutrophils [34]. In addition, experimental studies in which IFN-γ receptor was silenced suggested a more rapid onset of collagen-induced arthritis [35]. Although IFN-γ plays a key role in angiogenesis, there is no evidence that this cytokine is able to promote angiogenesis in OA.
Proteins from complement system have been found to play a role in OA, especially in early stages, as they were upregulated in both synovial membrane and fluid [23, 36]. Additionally, the deposition of the membrane attack complex (MAC, C5b-9) is correlated with the presence of inflammation on histology of synovial membrane, and it was present in chondrocytes in late OA [36]. MAC can lead to chondrocyte destruction as it stimulates catabolic events through the increase of leukocytes and, consequently, the production of MMP [23]. Also in the studies with experimental knockout models for C5 and C6, the joint damages were attenuated [36].
Cellular infiltrates from adaptive immune response have also been observed in synovial fluid from OA joints. Although the main cell type present in this infiltrate is CD3+ T cells, both CD4+ and CD8+ cells have also been found in OA [37]. Th1 cells, and consequently their secretory cytokines, such as IL-2 and INF-γ, appear to be expressed five times greater than Th2 in most of OA patients [37]. Based on lymphocyte aggregates, there is a suggestion of an active cell-mediated immune response since T-cells in lymphocytic aggregates in OA synovium were shown to bear early (CD69), intermediate (CD25 and CD38), and late (CD45RO) activation markers [38].
Inflammatory mediators observed in OA joints are thought to be the downstream effectors of the pathogenesis of the disease. Cytokines are among the most extensively studied mediators of inflammation. Several cytokines have been reported to play a role in the progression of OA, such as TNF, IL-1β, IL-6, IL-15, IL-17, IL-18, IL-4, and IL-10. Although their precise mechanism of action has not been completely elucidated yet, it has been proposed that their presence influences cartilage homeostasis as they induce catabolic events as well as inhibit anabolic processes [21, 39, 40].
Interleukin (IL)-1β and tumor necrosis factor (TNF) are considered the major mediators in the pathophysiology of OA. They both are secreted not only by immune cells, especially mononuclear cells, but also by chondrocytes and osteoblasts. In OA joints, these cytokines are increased in both synovial fluid and membrane. They are known to drive the inflammatory cascade, and their increased expression induces catabolic events as they enhance MMP [39]. IL-1β and TNF downregulate the synthesis of major extracellular matrix (ECM) components by inhibiting anabolic activities of chondrocytes [40] and reducing type II collagen production [41].
IL-1β is activated through the binding of its specific receptor type I (IL-1RI). Overexpression of IL-1RI in cartilage proximal to the macroscopic injury in OA joints resulting in increased binding of IL-1β was observed [42]. IL-1β has also been reported to be responsible for the catabolic events present in OA: its expression combined with TNF induces the production of MMP-1, -3, and -13 and stimulates the production of aggrecanases (ADAMTS)-4 and -5 in human and bovine chondrocytes [43, 44]. TNF receptor type I (TNFRI) is overexpressed in OA chondrocytes [45]. High levels of TNF-α in cartilage explants seem to inhibit the synthesis of proteoglycan and stimulate resorption [40].
In OA joint, IL-1β and TNF amplify the arthritic condition by inducing the production of proinflammatory cytokines, such as IL-6, IL-8, and monocyte chemoattractant protein 1. In addition, chondrocytes treated with IL-1β and TNF increase the production of nitric oxide (NO), cyclooxygenase 2 (COX-2), and prostaglandin E2 (PGE2), which contribute to articular inflammation and cartilage destruction as they enhance MMP activity, inhibit the production of anabolic products such as collagen and proteoglycan, and induce chondrocyte apoptosis [39].
The catabolic events observed (the catabolic events that occur due to the presence of…) in the presence of IL-1β and TNF are mediated through the activation of signaling pathways, including nuclear factor-κB (NF-κB) signaling. NF-κB pathway induces the expression of the genes related to the inflammatory mediators cited above and also contributes to the induction of MMP-1 and -13 and ADAMTS-4 [46]. However, some signaling pathways are involved in the downregulation of the IL-1β and TNF effects in OA, such as peroxisome proliferator-activated receptor-γ (PPAR-γ). The activation of PPAR-γ seems to reduce the progression of cartilage lesion in experimental models of OA as it assists the downregulation of inflammatory and catabolic responses mediated by IL-1β and TNF [47, 48].
IL-6 is a proinflammatory cytokine, whose signaling pathway involves the activation of receptors, such as membrane-bound IL-6 receptor (IL6R), soluble IL-6R (sIL-6R), and gp130, followed by the activation of STAT1 and STAT3 pathways [39]. In physiological conditions, the production of IL-6 by chondrocytes is considerably low. However, the exact mechanism of IL-6 action in OA is unknown, but its production can be stimulated by the number of cytokines and growth factors present in OA, including IL-1β, TGF-β, and PGE2 [25, 49].
Increased levels of IL-6 in synovial fluid and serum have been correlated with the severity of lesions in X-ray imaging [50]. In vitro studies have shown that IL-6, in combination with IL-1β and TNF, upregulates the production of MMP-1 and -13 in human and bovine chondrocytes and induces proteoglycan and type II collagen degradation [51, 52]. The effect of IL-6 in studies with animal models has shown uncertain results. IL-6 knockout mice revealed more advanced degenerative changes compared to wild-type animals [53]. However, when IL-6 was injected in the joint cavity of IL-6-deficient mice, the reduction in the loss of proteoglycans in the acute phase of inflammation was observed [54].
One of the most considered active components in OA is the change in subchondral bone tissue, and IL-6 has been a critical mediator in this regard. Its effect, together with IL-1β and TNF, is based on promoting osteoclast formation and, consequently, bone resorption [55]. In response to IL-6, osteoblasts stimulate the production of receptor activator of NF-κB ligand, IL-1β, and PGE2, which activate osteoclasts [56]. In addition, osteoblasts activated by these cytokines produce MMPs, which adversely affect the surrounding cartilage [57].
Despite a better documented involvement in rheumatoid arthritis [58], the knowledge regarding IL-15 and its action in OA is still poor. It acts based on the stimulation and proliferation of T cells and NK cells, and it may also induce the production of MMP [59]. IL-15 levels are elevated in synovial fluid in early stages of OA, and this concentration correlates with pain and severity of lesions seen on X-ray imaging [60, 61].
Due to its inflammatory effects, IL-17 family has been implied to play a role in OA [62]. IL-17 is mainly stimulated by CD4+ T cells and mast cells, which are present in the cellular infiltrates observed in OA joints [63]. Within the joints, IL-17 primarily targets chondrocytes and fibroblast-like synoviocytes, which express IL-17 receptor (IL-17R) on their surface [64]. It was reported that IL-17 is able to inhibit proteoglycan synthesis by chondrocytes and increase the production of MMPs [65]. Also, high levels of IL-17 in both serum and synovial fluid were correlated with radiographic lesions in OA [66].
The genetic correlation between IL-17 and OA was suggested: a polymorphism in the gene IL-17A G-197A could be associated with the susceptibility to the development of OA [67]. In addition, IL-17 is produced by a specific T cell lineage called T helper 17, and it is able to cause hypertrophy of synovial membrane as its presence influences the secretion of vascular endothelial growth factor (VEGF), which leads to excessive blood vessel formation [68]. It can also indirectly affect cartilage by inducing the production of cytokines responsible for tissue degradation, such as IL-1β, TNF, IL-6, NO, and PGE2 [64].
The active form of IL-18 results from the activation of caspase-1, which has been reported to be elevated in articular cartilage and synovium of OA, leading to great promotion of IL-18 and IL-1β. The production of IL-18 in joints is mainly determined by chondrocytes, osteoblasts, and macrophages [69]. IL-18 affects cartilage by upregulating the production of IL-18Rα on chondrocyte surface and stimulates excessive production of MMP-1, -3, and -13 [70]. Also, IL-18 negatively influences the production of proteoglycans, aggrecan, and type II collagen and may cause morphological changes typically observed in apoptotic processes [71, 72].
The increased concentration of IL-18 observed in synovial fluid, synovium, cartilage, and even blood serum from patients with OA has been correlated with the severity of lesions seen in radiographic imaging [73]. Also, studies have correlated the development of OA and lumbar disc degeneration with polymorphisms in the gene encoding IL-18 and its receptor (IL-18R) [74, 75].
Anti-inflammatory cytokines also present a role in the maintenance of OA. IL-4 is associated with chondroprotective effects as it is shown to reduce MMP production and, consequently, inhibit the degradation of proteoglycans in the articular cartilage [76]. However, chondrocytes from OA joints have shown a decreased susceptibility to this IL-4 protective effect, leaving the cartilage unprotected, quickening the degeneration via the action of the proinflammatory cytokines cited above [77]. In addition, a polymorphism in the gene encoding IL-4 and its main receptor (IL-4Rα) could predetermine the development of OA in hand and knee joints [78, 79]. It was also further reported that, when compared with healthy patients, OA patients present an elevated level of soluble IL-4Rα (sIL-4Rα) [80].
The activation of IL-4 depends on intracellular signal transduction by gradual phosphorylation of IL-4Rα, which leads to the expression of several proinflammatory genes [81]. IL-4 production is mainly determined by T cells, especially Th2, which are present in the cellular infiltrates observed in OA [37]. It was reported that IL-4 alone or in combination with IL-10 is able to reduce the production of diverse proinflammatory mediators, such as IL-1β, TNF-α receptors, IL-6, PGE2, and COX-2 [82, 83, 84].
Due to its anti-inflammatory features, IL-10 is another cytokine that presents chondroprotective effects, and it is linked to the release of IFN [62]. In vitro studies have shown increased proteoglycan and type II collagen syntheses after the administration of IL-10 in chondrocytes [62]. The protective effects that IL-10 exhibits are likely due to a stimulation of the synthesis of IL-1β antagonist and a tissue inhibition of MMP-1 (TIMP-1) [85]. Also, IL-10, as well as IL-4, reduces apoptotic events in chondrocytes and production of MMP [86, 87].
IL-10 induces the expression of bone morphogenetic protein-2 and -6 (BMP2 and BMP6), which are related to chondrogenesis as they belong to TGF-β family [88]. Together with BMP production, IL-10 activates signaling pathways, such as NKX-3.2/SOX9, that induce the differentiation of mesenchymal stem cells into chondrocytes [89]. Also, by reducing the expression of TNF-α receptors, IL-10 is able to attenuate the effect of TNF-α on synovial fibroblasts. A decrease in COX-2 production was also noted in the same study [90].
The secretion of IL-10 can be influenced by physical exercises. Patients with and without OA had synovial fluid and periarticular tissue harvested from their knee before, during, and after they underwent exercise practice for 3 hours. A significant increase in IL-10 levels was observed in these patients after the exercise. Although it is not clear what exact mechanism led to this result, this observation is likely attributed to an increase in intra-articular pressure and subsequent effects on cellular secretion [91, 92].
Chemokines comprise small proteins that act as chemoattractants to assist cells to migrate to injured tissue. Diverse chemokines have gained attention in the development of OA. Some of them including their receptors, such as IL-8, CCL5, CCL19, CCR1, CCR2, CCR3, and CCR5, may induce the production of MMP-3 by chondrocytes and increase the breakdown of cartilage matrix components, which trigger the onset of OA [60, 93]. However, some chemokines might present a protective role in OA, such as stromal cell-derived factor-1 (also called CXCL12), whose main function is to recruit mesenchymal stem cells to the injured area in order to promote tissue repair [94].
Several chemokines were reported to be overexpressed in OA, such as IL-8/CXCL-8, GROα/CXCL-1, MCP-1/CCL-2, RANTES/CCL-5, MIP-1α/CCL-3, and MIP-1β/CCL-4. Some of these chemokines are stimulated by IL-1β, which is upregulated in OA, and they induce MMP production upon binding to their ligands, causing tissue degradation [93]. Levels of INF-γ-inducible protein 10 (IP-10), also called as CXCL-10, in plasma and synovial fluid have been correlated with radiographic knee OA. CX3CL1, a serum fractalkine, has also been reported to be significantly elevated in severe knee OA in a study that compared OA patients with healthy patients [95].
To support the role of macrophage in the inflammatory response observed in OA, MCP-1, also known as chemokine ligand-2 (CCL2), has been reported to recruit macrophages into adipose tissue and atherosclerotic lesions [96]. Also, MCP-1 levels in both serum and synovial fluid has been associated with self-reported pain and disability in patients who present knee OA [97]. In addition, it was observed that, in severe knee OA, the levels of macrophage-derived chemokine (MDC) and IP-10 in synovial fluid were elevated, while eotaxin levels, an eosinophil chemotactic protein, were lower when compared with healthy patients [98].
Adipokines have been associated with the incidence and severity of OA [99]. In vitro studies reported that the presence of adipokines, such as leptin, adiponectin, visfatin, and resistin, increases the production of inflammatory mediators and also induces chondrolysis [99]. Although the exact mechanism of how these cytokines derived from adipose tissue act on arthritic joints has not yet been elucidated, researchers have studied the role of fat pad as a local inflammation mediator in OA, particularly in knee OA due to the infrapatellar fat pad, which has proven to be infiltrated with macrophages, lymphocytes, and granulocytes [100]. These findings support the thought that obesity supports the development of OA more through biochemical pathways rather than biomechanical overload risks on a weight-bearing joint.
The COX-2 enzyme is responsible for the production of lipid mediators, including PGE2 and leukotrienes, and it is also upregulated in OA joints. In addition, the overexpression of COX-2 in OA has been associated with the increased production of IL-1β, TNF, and IL-6 via toll-like receptor-4 (TLR-4) [101]. Besides assisting the production of MMPs and other functions already cited above, PGE2 is also involved in apoptosis and structural changes that characterize arthritic disease [102].
Leukotrienes have also been investigated for their role in OA. These mediators are converted from arachidonic acid, which also produces PGE2 via the activity of the enzyme phospholipase A2 [21]. Leukotrienes, mainly leukotriene B4 (LTB4), are present, to a lesser extent, in OA synovium, bone, and cartilage. Also, LTB4 has been reported to stimulate the production of IL-1β and TNF in arthritic synovium [103].
The cumulative evidences over the years have shown that increased expression of proinflammatory cytokines, in particular IL-1β, TNF, and IL-6, in cartilage as well as synovial fluid and membrane, has played a key role in the pathogenesis of OA. Inflammatory processes linked with immune responses have characterized OA as a complex disease and not as a simple age-related cartilage degeneration as it is thought to be. The understanding of individual roles of inflammatory mediators and their compounds is of utmost importance to target new therapies for OA, since the current options are elusive and may be noneffective, invasive, or even capable of presenting serious side effects. Due to advancements in molecular tools, the overall aim would be to dissect the role of each cytokine in the pathophysiology of OA and, together with drug delivery systems, to develop specific anticytokine therapy, given that inflammatory responses contribute substantially to OA maintenance.
The authors have no conflict of interest to declare.
IntechOpen Compacts provide a mid-length publishing format which bridges the gap between journal articles, book chapters and monographs, and cover content across all scientific disciplines. Compacts are the preferred publishing option for brief research reports on new topics, in-depth case studies, dissertations, or essays exploring new ideas, issues or broader topics on the research subject.
",metaTitle:"IntechOpen Compacts",metaDescription:"IntechOpen Compacts present a mid-length publishing format which bridges the gap between journal articles, book chapters, and monographs and covers content across all scientific disciplines.",metaKeywords:null,canonicalURL:"/page/compacts",contentRaw:'[{"type":"htmlEditorComponent","content":"Without sacrificing the quality of carefully edited and produced peer-reviewed content, Compacts are published as part of IntechOpen’s book collection but on a faster schedule, typically 4-6 weeks after acceptance. With an average of 132,000 visitors per week, publishing in Compacts not only guarantees high visibility but also facilitates international content sharing. As a fully Open Access publisher, the utilization of a CC BY NC 4.0 license means that other researchers will never have to pay permission fees and can adapt, use, and further build upon the material published in Compacts, eliminating any barriers to the further development of scientific research.
\\n\\nCOMPACTS-SHORT FORM MONOGRAPH
\\n\\nCOST
\\n\\n4,000 GBP Compacts Monograph - Short Form
\\n\\nThe final price will depend on the volume of the publication and includes project management, editorial and peer-review services, technical editing, language copyediting, cover design, book layout, book promotion and ISBN assignment.
\\n\\n*The price does not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate applicable in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT by providing us with their VAT registration number. This is made possible by the EU reverse charge method.
\\n\\nOptional Services
\\n\\nIntechOpen has collaborated with Enago, through its sister company, Ulatus – one of the world’s leading providers of book translation services. The services are designed to convey the essence of your work seamlessly to readers from across the globe in their own language. Enago’s expert translators incorporate cultural nuances in translations to make the content relevant for local audiences while retaining the original meaning and style. With a high degree of linguistic and subject expertise, Enago translators are equipped to handle all complex and multiple overlapping themes encompassed in a single book to deliver a superior quality of translation.
\\n\\nIntechOpen Authors that wish to use this service will receive a 20% discount on all translation work. For more information or a quote, please visit: https://www.enago.com/intech.
\\n\\nFUNDING
\\n\\nWe feel that financial barriers should never prevent researchers from publishing their research. Please consult our Open Access Funding page to explore funding opportunities and learn more about how you can finance your IntechOpen publication.
\\n\\nBENEFITS
\\n\\nPUBLISHING PROCESS STEPS
\\n\\nSee a complete overview and description of the steps involved in the publishing process here.
\\n\\nSEND YOUR PROPOSAL
\\n\\nIf you are interested in publishing your book with IntechOpen, please submit your book proposal by completing the Publishing Proposal Form.
\\n\\nNot sure if this is the right option for you? Please refer back to the main Publish with IntechOpen page or feel free to contact us directly at book.department@intechopen.com
\\n"}]'},components:[{type:"htmlEditorComponent",content:'Without sacrificing the quality of carefully edited and produced peer-reviewed content, Compacts are published as part of IntechOpen’s book collection but on a faster schedule, typically 4-6 weeks after acceptance. With an average of 132,000 visitors per week, publishing in Compacts not only guarantees high visibility but also facilitates international content sharing. As a fully Open Access publisher, the utilization of a CC BY NC 4.0 license means that other researchers will never have to pay permission fees and can adapt, use, and further build upon the material published in Compacts, eliminating any barriers to the further development of scientific research.
\n\nCOMPACTS-SHORT FORM MONOGRAPH
\n\nCOST
\n\n4,000 GBP Compacts Monograph - Short Form
\n\nThe final price will depend on the volume of the publication and includes project management, editorial and peer-review services, technical editing, language copyediting, cover design, book layout, book promotion and ISBN assignment.
\n\n*The price does not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate applicable in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT by providing us with their VAT registration number. This is made possible by the EU reverse charge method.
\n\nOptional Services
\n\nIntechOpen has collaborated with Enago, through its sister company, Ulatus – one of the world’s leading providers of book translation services. The services are designed to convey the essence of your work seamlessly to readers from across the globe in their own language. Enago’s expert translators incorporate cultural nuances in translations to make the content relevant for local audiences while retaining the original meaning and style. With a high degree of linguistic and subject expertise, Enago translators are equipped to handle all complex and multiple overlapping themes encompassed in a single book to deliver a superior quality of translation.
\n\nIntechOpen Authors that wish to use this service will receive a 20% discount on all translation work. For more information or a quote, please visit: https://www.enago.com/intech.
\n\nFUNDING
\n\nWe feel that financial barriers should never prevent researchers from publishing their research. Please consult our Open Access Funding page to explore funding opportunities and learn more about how you can finance your IntechOpen publication.
\n\nBENEFITS
\n\nPUBLISHING PROCESS STEPS
\n\nSee a complete overview and description of the steps involved in the publishing process here.
\n\nSEND YOUR PROPOSAL
\n\nIf you are interested in publishing your book with IntechOpen, please submit your book proposal by completing the Publishing Proposal Form.
\n\nNot sure if this is the right option for you? Please refer back to the main Publish with IntechOpen page or feel free to contact us directly at book.department@intechopen.com
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. From 2004 to 2011, he was a Research Assistant with the Communications Engineering Department at the University of Málaga. In 2011, he became an Assistant Professor in the same department. From 2012 to 2015, he was with Ericsson Spain, where he was working on geo-location\ntools for third generation mobile networks. Since 2015, he is a Marie-Curie fellow at the Denmark Technical University. His current research interests include the areas of mobile communication systems and channel modeling in addition to atmospheric optical communications, adaptive optics and statistics",institutionString:null,institution:{name:"University of Malaga",country:{name:"Spain"}}},{id:"6495",title:"Dr.",name:"Daniel",middleName:null,surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6495/images/1947_n.jpg",biography:"Daniel Eberli MD. Ph.D. is a scientific physician working in the translational field of urologic tissue engineering. He has a medical degree from the Medical School in Zurich, Switzerland, and a Ph.D. in Molecular Medicine from Wake Forest University, Winston Salem, NC. He currently has a faculty position at the Department of Urology at the University Hospital Zurich, where he devotes half of his time to patient care. He is a lecturer at the Medical School of Zurich and the Swiss Federal Institute of Technology. Together with his research team, he is working on novel biomaterials for bladder reconstruction, improving autonomic innervation, cellular treatment of incontinence and tracking of stem cells.",institutionString:null,institution:{name:"University Hospital of Zurich",country:{name:"Switzerland"}}},{id:"122240",title:"Prof.",name:"Frede",middleName:null,surname:"Blaabjerg",slug:"frede-blaabjerg",fullName:"Frede Blaabjerg",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Aalborg University",country:{name:"Denmark"}}},{id:"50823",title:"Prof.",name:"Hamid Reza",middleName:null,surname:"Karimi",slug:"hamid-reza-karimi",fullName:"Hamid Reza Karimi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Polytechnic University of Milan",country:{name:"Italy"}}},{id:"22128",title:"Dr.",name:"Harald",middleName:null,surname:"Haas",slug:"harald-haas",fullName:"Harald Haas",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Edinburgh",country:{name:"United Kingdom"}}},{id:"80399",title:"Dr.",name:"Huosheng",middleName:null,surname:"Hu",slug:"huosheng-hu",fullName:"Huosheng Hu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Essex",country:{name:"United Kingdom"}}},{id:"107729",title:"Prof.",name:"Joachim",middleName:null,surname:"Maier",slug:"joachim-maier",fullName:"Joachim Maier",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Max Planck Institute for Solid State Research",country:{name:"Germany"}}},{id:"51995",title:"Dr.",name:"Juan A.",middleName:"A.",surname:"Blanco",slug:"juan-a.-blanco",fullName:"Juan A. Blanco",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/51995/images/1076_n.jpg",biography:"Dr. Blanco is an Assistant Professor at the Public University of Navarre. His work is focused on the development and evaluation of ecological models to simulate the influences of management, climate and other ecological factors on tree growth. He is currently collaborating with research teams from Canada, Taiwan, USA, Spain, Cuba, and China in using ecological models to explore the effects of climate change, atmospheric pollution and alternative forest practices in natural and planted forest in boreal, temperate and tropical forests. His research has been applied in mining to optimize reclamation plans, in forestry to assess the potential for carbon sequestration and by government agencies to define local guidelines for long-term sustainable forest management. Among other topics related to forest ecology, Dr. Blanco has studied the influence of climate variations on tree growth and estimated the possible ecological consequences of climate change in forest ecosystems. He has also co-authored the first book dedicated exclusively to the use of hybrid ecological models in forest management, entitled “Forecasting Forest Futures” (Earthscan, London), edited three books on Climate Change effects, mitigation and adaptation (InTech, Rijeka), and three more on Forest Ecosystems, Biodiversity and Tropical Forests (InTech, Rijeka).",institutionString:null,institution:{name:"Universidad Publica De Navarra",country:{name:"Spain"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5311},{group:"region",caption:"Middle and South America",value:2,count:4814},{group:"region",caption:"Africa",value:3,count:1465},{group:"region",caption:"Asia",value:4,count:9355},{group:"region",caption:"Australia and Oceania",value:5,count:837},{group:"region",caption:"Europe",value:6,count:14773}],offset:12,limit:12,total:14778},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{hasNoEditors:"0",sort:"title",topicId:"16"},books:[{type:"book",id:"9442",title:"A Comprehensive Approach in Medico Legal Examination in Sexual Assault Cases",subtitle:null,isOpenForSubmission:!0,hash:"fa63d39e368a24bc2fe15356bed434b4",slug:null,bookSignature:"Dr. Adithi Shetty and Dr. B Suresh Shetty",coverURL:"https://cdn.intechopen.com/books/images_new/9442.jpg",editedByType:null,editors:[{id:"300329",title:"Dr.",name:"Adithi",surname:"Shetty",slug:"adithi-shetty",fullName:"Adithi Shetty"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9073",title:"Acne",subtitle:null,isOpenForSubmission:!0,hash:"6a7a4ab615c572fa07a704b44a35b0cf",slug:null,bookSignature:"Dr. Usma Iftikhar",coverURL:"https://cdn.intechopen.com/books/images_new/9073.jpg",editedByType:null,editors:[{id:"310225",title:"Dr.",name:"Usma",surname:"Iftikhar",slug:"usma-iftikhar",fullName:"Usma Iftikhar"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10169",title:"Alzheimer Disease",subtitle:null,isOpenForSubmission:!0,hash:"998e8960a0146fde43ea903efbd05ccd",slug:null,bookSignature:"Dr. Antonella Borreca",coverURL:"https://cdn.intechopen.com/books/images_new/10169.jpg",editedByType:null,editors:[{id:"192832",title:"Dr.",name:"Antonella",surname:"Borreca",slug:"antonella-borreca",fullName:"Antonella Borreca"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8595",title:"Anatomy of the Nervous System",subtitle:null,isOpenForSubmission:!0,hash:"f59dff4f2d8759cd16194142c427b691",slug:null,bookSignature:"Ph.D. Vicente Vanaclocha and Dr. Nieves Sáiz-Sapena",coverURL:"https://cdn.intechopen.com/books/images_new/8595.jpg",editedByType:null,editors:[{id:"199099",title:"Ph.D.",name:"Vicente",surname:"Vanaclocha",slug:"vicente-vanaclocha",fullName:"Vicente Vanaclocha"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9087",title:"Anemia",subtitle:null,isOpenForSubmission:!0,hash:"f94d3fb270e4af2b9813b12455424c22",slug:null,bookSignature:"Dr. Ota Fuchs",coverURL:"https://cdn.intechopen.com/books/images_new/9087.jpg",editedByType:null,editors:[{id:"36468",title:"Dr.",name:"Ota",surname:"Fuchs",slug:"ota-fuchs",fullName:"Ota Fuchs"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7987",title:"Angina",subtitle:null,isOpenForSubmission:!0,hash:"cc7b12af1cbe1a38236e4b59f6f728b5",slug:null,bookSignature:"Dr. Jeffrey Stephen Borer",coverURL:"https://cdn.intechopen.com/books/images_new/7987.jpg",editedByType:null,editors:[{id:"195160",title:"Dr.",name:"Jeffrey",surname:"Borer",slug:"jeffrey-borer",fullName:"Jeffrey Borer"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9151",title:"Ankle Injuries",subtitle:null,isOpenForSubmission:!0,hash:"5c900036edf7184f25d3a92229ae02b5",slug:null,bookSignature:"Prof. Arie M. Rijke",coverURL:"https://cdn.intechopen.com/books/images_new/9151.jpg",editedByType:null,editors:[{id:"245166",title:"Prof.",name:"Arie M.",surname:"Rijke",slug:"arie-m.-rijke",fullName:"Arie M. Rijke"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9521",title:"Antimicrobial Resistance",subtitle:null,isOpenForSubmission:!0,hash:"30949e78832e1afba5606634b52056ab",slug:null,bookSignature:"Prof. Mihai Mares and Dr. Romeo-Teodor Cristina",coverURL:"https://cdn.intechopen.com/books/images_new/9521.jpg",editedByType:null,editors:[{id:"88785",title:"Prof.",name:"Mihai",surname:"Mares",slug:"mihai-mares",fullName:"Mihai Mares"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9571",title:"Antisense Therapy - Recent Advances, New Perspectives and Clincal Applications",subtitle:null,isOpenForSubmission:!0,hash:"96f256f5bb2e750c7496b3c0b62cb95a",slug:null,bookSignature:"Prof. Pedro Baptista and Prof. Alexandra R Fernandes",coverURL:"https://cdn.intechopen.com/books/images_new/9571.jpg",editedByType:null,editors:[{id:"82671",title:"Prof.",name:"Pedro",surname:"Baptista",slug:"pedro-baptista",fullName:"Pedro Baptista"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9530",title:"Anxiety Disorders",subtitle:null,isOpenForSubmission:!0,hash:"702af230f376b968ca17900a9007cab9",slug:null,bookSignature:"Prof. Vladimir Kalinin",coverURL:"https://cdn.intechopen.com/books/images_new/9530.jpg",editedByType:null,editors:[{id:"31572",title:"Prof.",name:"Vladimir",surname:"Kalinin",slug:"vladimir-kalinin",fullName:"Vladimir Kalinin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9585",title:"Aortic Valve Disease",subtitle:null,isOpenForSubmission:!0,hash:"ef64f11e211621ecfe69c46e60e7ca3d",slug:null,bookSignature:" Michael S. S Firstenberg",coverURL:"https://cdn.intechopen.com/books/images_new/9585.jpg",editedByType:null,editors:[{id:"64343",title:null,name:"Michael S.",surname:"Firstenberg",slug:"michael-s.-firstenberg",fullName:"Michael S. Firstenberg"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9475",title:"Apheresis Science",subtitle:null,isOpenForSubmission:!0,hash:"6831e5bf01b9be99ebd33a7c665f2f86",slug:null,bookSignature:"Associate Prof. Anil Tombak",coverURL:"https://cdn.intechopen.com/books/images_new/9475.jpg",editedByType:null,editors:[{id:"202814",title:"Associate Prof.",name:"Anil",surname:"Tombak",slug:"anil-tombak",fullName:"Anil Tombak"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:35},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:33},{group:"topic",caption:"Business, Management and Economics",value:7,count:9},{group:"topic",caption:"Chemistry",value:8,count:28},{group:"topic",caption:"Computer and Information Science",value:9,count:27},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:15},{group:"topic",caption:"Engineering",value:11,count:75},{group:"topic",caption:"Environmental Sciences",value:12,count:13},{group:"topic",caption:"Immunology and Microbiology",value:13,count:3},{group:"topic",caption:"Materials Science",value:14,count:39},{group:"topic",caption:"Mathematics",value:15,count:14},{group:"topic",caption:"Medicine",value:16,count:143},{group:"topic",caption:"Nanotechnology and Nanomaterials",value:17,count:7},{group:"topic",caption:"Neuroscience",value:18,count:6},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:7},{group:"topic",caption:"Physics",value:20,count:26},{group:"topic",caption:"Psychology",value:21,count:2},{group:"topic",caption:"Robotics",value:22,count:6},{group:"topic",caption:"Social Sciences",value:23,count:14},{group:"topic",caption:"Technology",value:24,count:11},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:3},{group:"topic",caption:"Intelligent System",value:535,count:1},{group:"topic",caption:"Osteology",value:1414,count:1},{group:"topic",caption:"Polymer Chemistry",value:1415,count:1}],offset:12,limit:12,total:144},popularBooks:{featuredBooks:[{type:"book",id:"7878",title:"Advances in Extracorporeal Membrane Oxygenation",subtitle:"Volume 3",isOpenForSubmission:!1,hash:"f95bf990273d08098a00f9a1c2403cbe",slug:"advances-in-extracorporeal-membrane-oxygenation-volume-3",bookSignature:"Michael S. Firstenberg",coverURL:"https://cdn.intechopen.com/books/images_new/7878.jpg",editors:[{id:"64343",title:null,name:"Michael S.",middleName:"S",surname:"Firstenberg",slug:"michael-s.-firstenberg",fullName:"Michael S. Firstenberg"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7614",title:"Fourier Transforms",subtitle:"Century of Digitalization and Increasing Expectations",isOpenForSubmission:!1,hash:"ff3501657ae983a3b42fef1f7058ac91",slug:"fourier-transforms-century-of-digitalization-and-increasing-expectations",bookSignature:"Goran S. Nikoli? and Dragana Z. Markovi?-Nikoli?",coverURL:"https://cdn.intechopen.com/books/images_new/7614.jpg",editors:[{id:"23261",title:"Prof.",name:"Goran",middleName:"S.",surname:"Nikolic",slug:"goran-nikolic",fullName:"Goran Nikolic"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8299",title:"Timber Buildings and Sustainability",subtitle:null,isOpenForSubmission:!1,hash:"bccf2891cec38ed041724131aa34c25a",slug:"timber-buildings-and-sustainability",bookSignature:"Giovanna Concu",coverURL:"https://cdn.intechopen.com/books/images_new/8299.jpg",editors:[{id:"108709",title:"Dr.",name:"Giovanna",middleName:null,surname:"Concu",slug:"giovanna-concu",fullName:"Giovanna Concu"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7062",title:"Rhinosinusitis",subtitle:null,isOpenForSubmission:!1,hash:"14ed95e155b1e57a61827ca30b579d09",slug:"rhinosinusitis",bookSignature:"Balwant Singh Gendeh and Mirjana Turkalj",coverURL:"https://cdn.intechopen.com/books/images_new/7062.jpg",editors:[{id:"67669",title:"Prof.",name:"Balwant Singh",middleName:null,surname:"Gendeh",slug:"balwant-singh-gendeh",fullName:"Balwant Singh Gendeh"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7087",title:"Tendons",subtitle:null,isOpenForSubmission:!1,hash:"786abac0445c102d1399a1e727a2db7f",slug:"tendons",bookSignature:"Hasan Sözen",coverURL:"https://cdn.intechopen.com/books/images_new/7087.jpg",editors:[{id:"161402",title:"Dr.",name:"Hasan",middleName:null,surname:"Sözen",slug:"hasan-sozen",fullName:"Hasan Sözen"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7955",title:"Advances in Hematologic Malignancies",subtitle:null,isOpenForSubmission:!1,hash:"59ca1b09447fab4717a93e099f646d28",slug:"advances-in-hematologic-malignancies",bookSignature:"Gamal Abdul Hamid",coverURL:"https://cdn.intechopen.com/books/images_new/7955.jpg",editors:[{id:"36487",title:"Prof.",name:"Gamal",middleName:null,surname:"Abdul Hamid",slug:"gamal-abdul-hamid",fullName:"Gamal Abdul Hamid"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7701",title:"Assistive and Rehabilitation Engineering",subtitle:null,isOpenForSubmission:!1,hash:"4191b744b8af3b17d9a80026dcb0617f",slug:"assistive-and-rehabilitation-engineering",bookSignature:"Yves Rybarczyk",coverURL:"https://cdn.intechopen.com/books/images_new/7701.jpg",editors:[{id:"72920",title:"Prof.",name:"Yves",middleName:"Philippe",surname:"Rybarczyk",slug:"yves-rybarczyk",fullName:"Yves Rybarczyk"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7837",title:"Geriatric Medicine and Gerontology",subtitle:null,isOpenForSubmission:!1,hash:"e277d005b23536bcd9f8550046101979",slug:"geriatric-medicine-and-gerontology",bookSignature:"Edward T. Zawada Jr.",coverURL:"https://cdn.intechopen.com/books/images_new/7837.jpg",editors:[{id:"16344",title:"Dr.",name:"Edward T.",middleName:null,surname:"Zawada Jr.",slug:"edward-t.-zawada-jr.",fullName:"Edward T. Zawada Jr."}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7123",title:"Current Topics in Neglected Tropical Diseases",subtitle:null,isOpenForSubmission:!1,hash:"61c627da05b2ace83056d11357bdf361",slug:"current-topics-in-neglected-tropical-diseases",bookSignature:"Alfonso J. Rodriguez-Morales",coverURL:"https://cdn.intechopen.com/books/images_new/7123.jpg",editors:[{id:"131400",title:"Dr.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7610",title:"Renewable and Sustainable Composites",subtitle:null,isOpenForSubmission:!1,hash:"c2de26c3d329c54f093dc3f05417500a",slug:"renewable-and-sustainable-composites",bookSignature:"António B. Pereira and Fábio A. O. Fernandes",coverURL:"https://cdn.intechopen.com/books/images_new/7610.jpg",editors:[{id:"211131",title:"Prof.",name:"António",middleName:"Bastos",surname:"Pereira",slug:"antonio-pereira",fullName:"António Pereira"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8416",title:"Non-Equilibrium Particle Dynamics",subtitle:null,isOpenForSubmission:!1,hash:"2c3add7639dcd1cb442cb4313ea64e3a",slug:"non-equilibrium-particle-dynamics",bookSignature:"Albert S. Kim",coverURL:"https://cdn.intechopen.com/books/images_new/8416.jpg",editors:[{id:"21045",title:"Prof.",name:"Albert S.",middleName:null,surname:"Kim",slug:"albert-s.-kim",fullName:"Albert S. Kim"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8463",title:"Pediatric Surgery, Flowcharts and Clinical Algorithms",subtitle:null,isOpenForSubmission:!1,hash:"23f39beea4d557b0ae424e2eaf82bf5e",slug:"pediatric-surgery-flowcharts-and-clinical-algorithms",bookSignature:"Sameh Shehata",coverURL:"https://cdn.intechopen.com/books/images_new/8463.jpg",editors:[{id:"37518",title:"Prof.",name:"Sameh",middleName:null,surname:"Shehata",slug:"sameh-shehata",fullName:"Sameh Shehata"}],productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:4385},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"7878",title:"Advances in Extracorporeal Membrane Oxygenation",subtitle:"Volume 3",isOpenForSubmission:!1,hash:"f95bf990273d08098a00f9a1c2403cbe",slug:"advances-in-extracorporeal-membrane-oxygenation-volume-3",bookSignature:"Michael S. Firstenberg",coverURL:"https://cdn.intechopen.com/books/images_new/7878.jpg",editors:[{id:"64343",title:null,name:"Michael S.",middleName:"S",surname:"Firstenberg",slug:"michael-s.-firstenberg",fullName:"Michael S. Firstenberg"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7614",title:"Fourier Transforms",subtitle:"Century of Digitalization and Increasing Expectations",isOpenForSubmission:!1,hash:"ff3501657ae983a3b42fef1f7058ac91",slug:"fourier-transforms-century-of-digitalization-and-increasing-expectations",bookSignature:"Goran S. Nikoli? and Dragana Z. Markovi?-Nikoli?",coverURL:"https://cdn.intechopen.com/books/images_new/7614.jpg",editors:[{id:"23261",title:"Prof.",name:"Goran",middleName:"S.",surname:"Nikolic",slug:"goran-nikolic",fullName:"Goran Nikolic"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8299",title:"Timber Buildings and Sustainability",subtitle:null,isOpenForSubmission:!1,hash:"bccf2891cec38ed041724131aa34c25a",slug:"timber-buildings-and-sustainability",bookSignature:"Giovanna Concu",coverURL:"https://cdn.intechopen.com/books/images_new/8299.jpg",editors:[{id:"108709",title:"Dr.",name:"Giovanna",middleName:null,surname:"Concu",slug:"giovanna-concu",fullName:"Giovanna Concu"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7062",title:"Rhinosinusitis",subtitle:null,isOpenForSubmission:!1,hash:"14ed95e155b1e57a61827ca30b579d09",slug:"rhinosinusitis",bookSignature:"Balwant Singh Gendeh and Mirjana Turkalj",coverURL:"https://cdn.intechopen.com/books/images_new/7062.jpg",editors:[{id:"67669",title:"Prof.",name:"Balwant Singh",middleName:null,surname:"Gendeh",slug:"balwant-singh-gendeh",fullName:"Balwant Singh Gendeh"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7087",title:"Tendons",subtitle:null,isOpenForSubmission:!1,hash:"786abac0445c102d1399a1e727a2db7f",slug:"tendons",bookSignature:"Hasan Sözen",coverURL:"https://cdn.intechopen.com/books/images_new/7087.jpg",editors:[{id:"161402",title:"Dr.",name:"Hasan",middleName:null,surname:"Sözen",slug:"hasan-sozen",fullName:"Hasan Sözen"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7955",title:"Advances in Hematologic Malignancies",subtitle:null,isOpenForSubmission:!1,hash:"59ca1b09447fab4717a93e099f646d28",slug:"advances-in-hematologic-malignancies",bookSignature:"Gamal Abdul Hamid",coverURL:"https://cdn.intechopen.com/books/images_new/7955.jpg",editors:[{id:"36487",title:"Prof.",name:"Gamal",middleName:null,surname:"Abdul Hamid",slug:"gamal-abdul-hamid",fullName:"Gamal Abdul Hamid"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7701",title:"Assistive and Rehabilitation Engineering",subtitle:null,isOpenForSubmission:!1,hash:"4191b744b8af3b17d9a80026dcb0617f",slug:"assistive-and-rehabilitation-engineering",bookSignature:"Yves Rybarczyk",coverURL:"https://cdn.intechopen.com/books/images_new/7701.jpg",editors:[{id:"72920",title:"Prof.",name:"Yves",middleName:"Philippe",surname:"Rybarczyk",slug:"yves-rybarczyk",fullName:"Yves Rybarczyk"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7837",title:"Geriatric Medicine and Gerontology",subtitle:null,isOpenForSubmission:!1,hash:"e277d005b23536bcd9f8550046101979",slug:"geriatric-medicine-and-gerontology",bookSignature:"Edward T. Zawada Jr.",coverURL:"https://cdn.intechopen.com/books/images_new/7837.jpg",editors:[{id:"16344",title:"Dr.",name:"Edward T.",middleName:null,surname:"Zawada Jr.",slug:"edward-t.-zawada-jr.",fullName:"Edward T. Zawada Jr."}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7123",title:"Current Topics in Neglected Tropical Diseases",subtitle:null,isOpenForSubmission:!1,hash:"61c627da05b2ace83056d11357bdf361",slug:"current-topics-in-neglected-tropical-diseases",bookSignature:"Alfonso J. Rodriguez-Morales",coverURL:"https://cdn.intechopen.com/books/images_new/7123.jpg",editors:[{id:"131400",title:"Dr.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7610",title:"Renewable and Sustainable Composites",subtitle:null,isOpenForSubmission:!1,hash:"c2de26c3d329c54f093dc3f05417500a",slug:"renewable-and-sustainable-composites",bookSignature:"António B. Pereira and Fábio A. O. Fernandes",coverURL:"https://cdn.intechopen.com/books/images_new/7610.jpg",editors:[{id:"211131",title:"Prof.",name:"António",middleName:"Bastos",surname:"Pereira",slug:"antonio-pereira",fullName:"António Pereira"}],productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"8463",title:"Pediatric Surgery, Flowcharts and Clinical Algorithms",subtitle:null,isOpenForSubmission:!1,hash:"23f39beea4d557b0ae424e2eaf82bf5e",slug:"pediatric-surgery-flowcharts-and-clinical-algorithms",bookSignature:"Sameh Shehata",coverURL:"https://cdn.intechopen.com/books/images_new/8463.jpg",editedByType:"Edited by",editors:[{id:"37518",title:"Prof.",name:"Sameh",middleName:null,surname:"Shehata",slug:"sameh-shehata",fullName:"Sameh Shehata"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7187",title:"Osteosarcoma",subtitle:"Diagnosis, Mechanisms, and Translational Developments",isOpenForSubmission:!1,hash:"89096359b754beb806eca4c6d8aacaba",slug:"osteosarcoma-diagnosis-mechanisms-and-translational-developments",bookSignature:"Matthew Gregory Cable and Robert Lawrence Randall",coverURL:"https://cdn.intechopen.com/books/images_new/7187.jpg",editedByType:"Edited by",editors:[{id:"265693",title:"Dr.",name:"Matthew Gregory",middleName:null,surname:"Cable",slug:"matthew-gregory-cable",fullName:"Matthew Gregory Cable"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7955",title:"Advances in Hematologic Malignancies",subtitle:null,isOpenForSubmission:!1,hash:"59ca1b09447fab4717a93e099f646d28",slug:"advances-in-hematologic-malignancies",bookSignature:"Gamal Abdul Hamid",coverURL:"https://cdn.intechopen.com/books/images_new/7955.jpg",editedByType:"Edited by",editors:[{id:"36487",title:"Prof.",name:"Gamal",middleName:null,surname:"Abdul Hamid",slug:"gamal-abdul-hamid",fullName:"Gamal Abdul Hamid"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7701",title:"Assistive and Rehabilitation Engineering",subtitle:null,isOpenForSubmission:!1,hash:"4191b744b8af3b17d9a80026dcb0617f",slug:"assistive-and-rehabilitation-engineering",bookSignature:"Yves Rybarczyk",coverURL:"https://cdn.intechopen.com/books/images_new/7701.jpg",editedByType:"Edited by",editors:[{id:"72920",title:"Prof.",name:"Yves",middleName:"Philippe",surname:"Rybarczyk",slug:"yves-rybarczyk",fullName:"Yves Rybarczyk"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7726",title:"Swarm Intelligence",subtitle:"Recent Advances, New Perspectives and Applications",isOpenForSubmission:!1,hash:"e7ea7e74ce7a7a8e5359629e07c68d31",slug:"swarm-intelligence-recent-advances-new-perspectives-and-applications",bookSignature:"Javier Del Ser, Esther Villar and Eneko Osaba",coverURL:"https://cdn.intechopen.com/books/images_new/7726.jpg",editedByType:"Edited by",editors:[{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8256",title:"Distillation",subtitle:"Modelling, Simulation and Optimization",isOpenForSubmission:!1,hash:"c76af109f83e14d915e5cb3949ae8b80",slug:"distillation-modelling-simulation-and-optimization",bookSignature:"Vilmar Steffen",coverURL:"https://cdn.intechopen.com/books/images_new/8256.jpg",editedByType:"Edited by",editors:[{id:"189035",title:"Dr.",name:"Vilmar",middleName:null,surname:"Steffen",slug:"vilmar-steffen",fullName:"Vilmar Steffen"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7240",title:"Growing and Handling of Bacterial Cultures",subtitle:null,isOpenForSubmission:!1,hash:"a76c3ef7718c0b72d0128817cdcbe6e3",slug:"growing-and-handling-of-bacterial-cultures",bookSignature:"Madhusmita Mishra",coverURL:"https://cdn.intechopen.com/books/images_new/7240.jpg",editedByType:"Edited by",editors:[{id:"204267",title:"Dr.",name:"Madhusmita",middleName:null,surname:"Mishra",slug:"madhusmita-mishra",fullName:"Madhusmita Mishra"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8299",title:"Timber Buildings and Sustainability",subtitle:null,isOpenForSubmission:!1,hash:"bccf2891cec38ed041724131aa34c25a",slug:"timber-buildings-and-sustainability",bookSignature:"Giovanna Concu",coverURL:"https://cdn.intechopen.com/books/images_new/8299.jpg",editedByType:"Edited by",editors:[{id:"108709",title:"Dr.",name:"Giovanna",middleName:null,surname:"Concu",slug:"giovanna-concu",fullName:"Giovanna Concu"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7062",title:"Rhinosinusitis",subtitle:null,isOpenForSubmission:!1,hash:"14ed95e155b1e57a61827ca30b579d09",slug:"rhinosinusitis",bookSignature:"Balwant Singh Gendeh and Mirjana Turkalj",coverURL:"https://cdn.intechopen.com/books/images_new/7062.jpg",editedByType:"Edited by",editors:[{id:"67669",title:"Prof.",name:"Balwant Singh",middleName:null,surname:"Gendeh",slug:"balwant-singh-gendeh",fullName:"Balwant Singh Gendeh"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7837",title:"Geriatric Medicine and Gerontology",subtitle:null,isOpenForSubmission:!1,hash:"e277d005b23536bcd9f8550046101979",slug:"geriatric-medicine-and-gerontology",bookSignature:"Edward T. Zawada Jr.",coverURL:"https://cdn.intechopen.com/books/images_new/7837.jpg",editedByType:"Edited by",editors:[{id:"16344",title:"Dr.",name:"Edward T.",middleName:null,surname:"Zawada Jr.",slug:"edward-t.-zawada-jr.",fullName:"Edward T. Zawada Jr."}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"48",title:"Conservation Genetics",slug:"conservation-genetics",parent:{title:"Biochemistry, Genetics and Molecular Biology",slug:"biochemistry-genetics-and-molecular-biology"},numberOfBooks:1,numberOfAuthorsAndEditors:40,numberOfWosCitations:19,numberOfCrossrefCitations:15,numberOfDimensionsCitations:41,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"conservation-genetics",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"1610",title:"Analysis of Genetic Variation in Animals",subtitle:null,isOpenForSubmission:!1,hash:"2dbc70699ec1ca38dc2175c6aeebe710",slug:"analysis-of-genetic-variation-in-animals",bookSignature:"Mahmut Caliskan",coverURL:"https://cdn.intechopen.com/books/images_new/1610.jpg",editedByType:"Edited by",editors:[{id:"51528",title:"Prof.",name:"Mahmut",middleName:null,surname:"Caliskan",slug:"mahmut-caliskan",fullName:"Mahmut Caliskan"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:1,mostCitedChapters:[{id:"29265",doi:"10.5772/35455",title:"Shark DNA Forensics: Applications and Impacts on Genetic Diversity",slug:"shark-dna-forensics-applications-and-impacts-on-genetic-diversity",totalDownloads:3262,totalCrossrefCites:1,totalDimensionsCites:7,book:{slug:"analysis-of-genetic-variation-in-animals",title:"Analysis of Genetic Variation in Animals",fullTitle:"Analysis of Genetic Variation in Animals"},signatures:"Luis Fernando Rodrigues-Filho, Danillo Pinhal, Davidson Sodré and Marcelo Vallinoto",authors:[{id:"104502",title:"Prof.",name:"Marcelo",middleName:null,surname:"Vallinoto",slug:"marcelo-vallinoto",fullName:"Marcelo Vallinoto"},{id:"104511",title:"Dr.",name:"Danillo",middleName:null,surname:"Pinhal",slug:"danillo-pinhal",fullName:"Danillo Pinhal"},{id:"104512",title:"Dr.",name:"Luis Fernando",middleName:null,surname:"Rodrigues-Filho",slug:"luis-fernando-rodrigues-filho",fullName:"Luis Fernando Rodrigues-Filho"},{id:"104514",title:"MSc.",name:"Davidson Clayton",middleName:null,surname:"Azevedo Sodré",slug:"davidson-clayton-azevedo-sodre",fullName:"Davidson Clayton Azevedo Sodré"}]},{id:"29252",doi:"10.5772/34554",title:"Genetic Characterization of Albanian Sheep Breeds by Microsatellite Markers",slug:"genetic-characterization-of-albanian-sheep-breeds-by-microsatellite-markers",totalDownloads:3373,totalCrossrefCites:4,totalDimensionsCites:6,book:{slug:"analysis-of-genetic-variation-in-animals",title:"Analysis of Genetic Variation in Animals",fullTitle:"Analysis of Genetic Variation in Animals"},signatures:"Anila Hoda and Paolo Ajmone Marsan",authors:[{id:"100682",title:"Prof.",name:"Anila",middleName:null,surname:"Hoda",slug:"anila-hoda",fullName:"Anila Hoda"},{id:"130583",title:"Prof.",name:"Paolo",middleName:null,surname:"Ajmone Marsan",slug:"paolo-ajmone-marsan",fullName:"Paolo Ajmone Marsan"}]},{id:"29267",doi:"10.5772/34089",title:"Aquatic Introductions and Genetic Founder Effects: How do Parasites Compare to Hosts?",slug:"security-limitations-of-spectral-amplitude-coding-based-on-modified-quadratic-congruence-code-system",totalDownloads:1910,totalCrossrefCites:2,totalDimensionsCites:5,book:{slug:"analysis-of-genetic-variation-in-animals",title:"Analysis of Genetic Variation in Animals",fullTitle:"Analysis of Genetic Variation in Animals"},signatures:"April M. H. Blakeslee and Amy E. Fowler",authors:[{id:"98632",title:"Dr.",name:"April",middleName:null,surname:"Blakeslee",slug:"april-blakeslee",fullName:"April Blakeslee"},{id:"103338",title:"Dr.",name:"Amy",middleName:null,surname:"Fowler",slug:"amy-fowler",fullName:"Amy Fowler"}]}],mostDownloadedChaptersLast30Days:[{id:"29261",title:"Landscape Genomics in Livestock",slug:"landscape-genomics-in-livestock",totalDownloads:2284,totalCrossrefCites:0,totalDimensionsCites:1,book:{slug:"analysis-of-genetic-variation-in-animals",title:"Analysis of Genetic Variation in Animals",fullTitle:"Analysis of Genetic Variation in Animals"},signatures:"Lorraine Pariset, Stephane Joost, Maria Gargani and Alessio Valentini",authors:[{id:"93248",title:"Dr.",name:"Lorraine",middleName:null,surname:"Pariset",slug:"lorraine-pariset",fullName:"Lorraine Pariset"},{id:"103844",title:"Dr.",name:"Stephane",middleName:null,surname:"Joost",slug:"stephane-joost",fullName:"Stephane Joost"},{id:"103848",title:"Dr.",name:"Maria",middleName:null,surname:"Gargani",slug:"maria-gargani",fullName:"Maria Gargani"},{id:"103849",title:"Prof.",name:"Alessio",middleName:null,surname:"Valentini",slug:"alessio-valentini",fullName:"Alessio Valentini"}]},{id:"29255",title:"Interspecific and Intraspecific Genetic Diversity of Thunnus Species",slug:"interspecific-and-intraspecific-genetic-diversity-of-thunnus-species",totalDownloads:3172,totalCrossrefCites:3,totalDimensionsCites:4,book:{slug:"analysis-of-genetic-variation-in-animals",title:"Analysis of Genetic Variation in Animals",fullTitle:"Analysis of Genetic Variation in Animals"},signatures:"Mei-Chen Tseng, Chuen-Tan Jean, Peter J. Smith and Yin-Huei Hung",authors:[{id:"96064",title:"Prof.",name:"Mei-Chen",middleName:null,surname:"Tseng",slug:"mei-chen-tseng",fullName:"Mei-Chen Tseng"}]},{id:"29259",title:"Genetic Diversity and Genetic Heterogeneity of Bigfin Reef Squid “Sepioteuthis lessoniana” Species Complex in Northwestern Pacific Ocean",slug:"genetic-diversity-and-genetic-heterogeneity-of-bigfin-reef-squid-sepioteuthis-lessoniana-species-com",totalDownloads:1752,totalCrossrefCites:2,totalDimensionsCites:5,book:{slug:"analysis-of-genetic-variation-in-animals",title:"Analysis of Genetic Variation in Animals",fullTitle:"Analysis of Genetic Variation in Animals"},signatures:"Hideyuki Imai and Misuzu Aoki",authors:[{id:"102652",title:"Dr.",name:"Hideyuki",middleName:null,surname:"Imai",slug:"hideyuki-imai",fullName:"Hideyuki Imai"}]},{id:"29265",title:"Shark DNA Forensics: Applications and Impacts on Genetic Diversity",slug:"shark-dna-forensics-applications-and-impacts-on-genetic-diversity",totalDownloads:3262,totalCrossrefCites:1,totalDimensionsCites:7,book:{slug:"analysis-of-genetic-variation-in-animals",title:"Analysis of Genetic Variation in Animals",fullTitle:"Analysis of Genetic Variation in Animals"},signatures:"Luis Fernando Rodrigues-Filho, Danillo Pinhal, Davidson Sodré and Marcelo Vallinoto",authors:[{id:"104502",title:"Prof.",name:"Marcelo",middleName:null,surname:"Vallinoto",slug:"marcelo-vallinoto",fullName:"Marcelo Vallinoto"},{id:"104511",title:"Dr.",name:"Danillo",middleName:null,surname:"Pinhal",slug:"danillo-pinhal",fullName:"Danillo Pinhal"},{id:"104512",title:"Dr.",name:"Luis Fernando",middleName:null,surname:"Rodrigues-Filho",slug:"luis-fernando-rodrigues-filho",fullName:"Luis Fernando Rodrigues-Filho"},{id:"104514",title:"MSc.",name:"Davidson Clayton",middleName:null,surname:"Azevedo Sodré",slug:"davidson-clayton-azevedo-sodre",fullName:"Davidson Clayton Azevedo Sodré"}]},{id:"29268",title:"Estimating the Worth of Traits of Indigenous Breeds of Cattle in Ethiopia",slug:"estimating-the-worth-of-traits-of-indigenous-breeds-of-cattle-in-ethiopia",totalDownloads:2896,totalCrossrefCites:0,totalDimensionsCites:2,book:{slug:"analysis-of-genetic-variation-in-animals",title:"Analysis of Genetic Variation in Animals",fullTitle:"Analysis of Genetic Variation in Animals"},signatures:"Girma T. Kassie, Awudu Abdulai and Clemens Wollny",authors:[{id:"93081",title:"Dr.",name:"Girma",middleName:null,surname:"Kassie",slug:"girma-kassie",fullName:"Girma Kassie"},{id:"99469",title:"Prof.",name:"Awudu",middleName:null,surname:"Abdulai",slug:"awudu-abdulai",fullName:"Awudu Abdulai"},{id:"99470",title:"Prof.",name:"Clemens",middleName:null,surname:"Wollny",slug:"clemens-wollny",fullName:"Clemens Wollny"}]},{id:"29258",title:"Genetic Diversity and Evolution of Marine Animals Isolated in Marine Lakes",slug:"genetic-diversity-and-evolution-of-marine-animals-isolated-in-marine-lakes",totalDownloads:2344,totalCrossrefCites:0,totalDimensionsCites:1,book:{slug:"analysis-of-genetic-variation-in-animals",title:"Analysis of Genetic Variation in Animals",fullTitle:"Analysis of Genetic Variation in Animals"},signatures:"Naoto Hanzawa, Ryo O. Gotoh, Hidekatsu Sekimoto, Tadasuke V. Goto, Satoru N. Chiba, Kaoru Kuriiwa and Hidetoshi B. Tamate",authors:[{id:"100088",title:"Prof.",name:"Naoto",middleName:null,surname:"Hanzawa",slug:"naoto-hanzawa",fullName:"Naoto Hanzawa"},{id:"104133",title:"PhD.",name:"Ryo",middleName:"O",surname:"Gotoh",slug:"ryo-gotoh",fullName:"Ryo Gotoh"},{id:"104134",title:"Dr.",name:"Tadasuke V.",middleName:null,surname:"Goto",slug:"tadasuke-v.-goto",fullName:"Tadasuke V. Goto"},{id:"104137",title:"MSc.",name:"Hidekatsu",middleName:null,surname:"Sekimoto",slug:"hidekatsu-sekimoto",fullName:"Hidekatsu Sekimoto"},{id:"104139",title:"Prof.",name:"Hidetoshi B.",middleName:null,surname:"Tamate",slug:"hidetoshi-b.-tamate",fullName:"Hidetoshi B. Tamate"},{id:"130516",title:"Dr.",name:"Satoru",middleName:"N",surname:"Chiba",slug:"satoru-chiba",fullName:"Satoru Chiba"},{id:"130517",title:"Dr.",name:"Kaoru",middleName:null,surname:"Kuriiwa",slug:"kaoru-kuriiwa",fullName:"Kaoru Kuriiwa"}]},{id:"29252",title:"Genetic Characterization of Albanian Sheep Breeds by Microsatellite Markers",slug:"genetic-characterization-of-albanian-sheep-breeds-by-microsatellite-markers",totalDownloads:3373,totalCrossrefCites:4,totalDimensionsCites:6,book:{slug:"analysis-of-genetic-variation-in-animals",title:"Analysis of Genetic Variation in Animals",fullTitle:"Analysis of Genetic Variation in Animals"},signatures:"Anila Hoda and Paolo Ajmone Marsan",authors:[{id:"100682",title:"Prof.",name:"Anila",middleName:null,surname:"Hoda",slug:"anila-hoda",fullName:"Anila Hoda"},{id:"130583",title:"Prof.",name:"Paolo",middleName:null,surname:"Ajmone Marsan",slug:"paolo-ajmone-marsan",fullName:"Paolo Ajmone Marsan"}]},{id:"29262",title:"Managing the Genetic Resources in the Intensive Stock Enhancement Program Carried out on Black Sea Bream in Hiroshima Bay, Japan",slug:"managing-the-genetic-resources-in-the-intensive-stock-enhancement-program-carried-out-on-black-sea-b",totalDownloads:1785,totalCrossrefCites:1,totalDimensionsCites:3,book:{slug:"analysis-of-genetic-variation-in-animals",title:"Analysis of Genetic Variation in Animals",fullTitle:"Analysis of Genetic Variation in Animals"},signatures:"Enrique Blanco Gonzalez and Tetsuya Umino",authors:[{id:"117464",title:"Dr.",name:"Tetsuya",middleName:null,surname:"Umino",slug:"tetsuya-umino",fullName:"Tetsuya Umino"},{id:"123649",title:"Dr.",name:"Enrique",middleName:null,surname:"Blanco Gonzalez",slug:"enrique-blanco-gonzalez",fullName:"Enrique Blanco Gonzalez"}]},{id:"29257",title:"Molecular Markers and Genetic Diversity in Neotropical Felids",slug:"molecular-markers-and-genetic-diversity-in-neotropical-felids",totalDownloads:2608,totalCrossrefCites:0,totalDimensionsCites:1,book:{slug:"analysis-of-genetic-variation-in-animals",title:"Analysis of Genetic Variation in Animals",fullTitle:"Analysis of Genetic Variation in Animals"},signatures:"Alexeia Barufatti Grisolia and Vanessa Roma Moreno-Cotulio",authors:[{id:"98721",title:"Dr.",name:"Alexeia",middleName:"Barufatti",surname:"Grisolia",slug:"alexeia-grisolia",fullName:"Alexeia Grisolia"},{id:"128459",title:"Dr.",name:"Vanessa",middleName:null,surname:"Moreno Cotulio",slug:"vanessa-moreno-cotulio",fullName:"Vanessa Moreno Cotulio"}]},{id:"29253",title:"Genetic Characterization of Romanian Local Breeds Using Microsatellite Markers",slug:"genetic-characterization-of-romanian-local-breeds-using-microsatellite-markers",totalDownloads:2363,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"analysis-of-genetic-variation-in-animals",title:"Analysis of Genetic Variation in Animals",fullTitle:"Analysis of Genetic Variation in Animals"},signatures:"Georgescu Sergiu Emil and Costache Marieta",authors:[{id:"93366",title:"Dr.",name:"Sergiu",middleName:"Emil",surname:"Georgescu",slug:"sergiu-georgescu",fullName:"Sergiu Georgescu"},{id:"102042",title:"Prof.",name:"Marieta",middleName:null,surname:"Costache",slug:"marieta-costache",fullName:"Marieta Costache"}]}],onlineFirstChaptersFilter:{topicSlug:"conservation-genetics",limit:3,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[{type:"book",id:"6837",title:"Lithium-ion Batteries - Thin Film for Energy Materials and Devices",subtitle:null,isOpenForSubmission:!0,hash:"ea7789260b319b9a4b472257f57bfeb5",slug:null,bookSignature:"Prof. Mitsunobu Sato, Dr. Li Lu and Dr. Hiroki Nagai",coverURL:"https://cdn.intechopen.com/books/images_new/6837.jpg",editedByType:null,editors:[{id:"179615",title:"Prof.",name:"Mitsunobu",middleName:null,surname:"Sato",slug:"mitsunobu-sato",fullName:"Mitsunobu Sato"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9423",title:"Applications of Artificial Intelligence in Process Industry Automation, Heat and Power Generation and Smart Manufacturing",subtitle:null,isOpenForSubmission:!0,hash:"10ac8fb0bdbf61044395963028653d21",slug:null,bookSignature:"Prof. Konstantinos G. Kyprianidis and Prof. Erik Dahlquist",coverURL:"https://cdn.intechopen.com/books/images_new/9423.jpg",editedByType:null,editors:[{id:"35868",title:"Prof.",name:"Konstantinos",middleName:"G.",surname:"Kyprianidis",slug:"konstantinos-kyprianidis",fullName:"Konstantinos Kyprianidis"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9428",title:"New Trends in the Use of Artificial Intelligence for the Industry 4.0",subtitle:null,isOpenForSubmission:!0,hash:"9e089eec484ce8e9eb32198c2d8b34ea",slug:null,bookSignature:"Dr. Luis Romeral Martinez, Dr. Roque A. Osornio-Rios and Dr. Miguel Delgado Prieto",coverURL:"https://cdn.intechopen.com/books/images_new/9428.jpg",editedByType:null,editors:[{id:"86501",title:"Dr.",name:"Luis",middleName:null,surname:"Romeral Martinez",slug:"luis-romeral-martinez",fullName:"Luis Romeral Martinez"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10107",title:"Artificial Intelligence in Oncology Drug Discovery & Development",subtitle:null,isOpenForSubmission:!0,hash:"043c178c3668865ab7d35dcb2ceea794",slug:null,bookSignature:"Dr. John Cassidy and Dr. Belle Taylor",coverURL:"https://cdn.intechopen.com/books/images_new/10107.jpg",editedByType:null,editors:[{id:"244455",title:"Dr.",name:"John",middleName:null,surname:"Cassidy",slug:"john-cassidy",fullName:"John Cassidy"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8903",title:"Carbon Based Material for Environmental Protection and Remediation",subtitle:null,isOpenForSubmission:!0,hash:"19da699b370f320eca63ef2ba02f745d",slug:null,bookSignature:"Dr. Mattia Bartoli and Dr. Marco Frediani",coverURL:"https://cdn.intechopen.com/books/images_new/8903.jpg",editedByType:null,editors:[{id:"188999",title:"Dr.",name:"Mattia",middleName:null,surname:"Bartoli",slug:"mattia-bartoli",fullName:"Mattia Bartoli"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10132",title:"Applied Computational Near-surface Geophysics - From Integral and Derivative Formulas to MATLAB Codes",subtitle:null,isOpenForSubmission:!0,hash:"38cdbbb671df620b36ee96af1d9a3a90",slug:null,bookSignature:"Dr. Afshin Aghayan",coverURL:"https://cdn.intechopen.com/books/images_new/10132.jpg",editedByType:null,editors:[{id:"311030",title:"Dr.",name:"Afshin",middleName:null,surname:"Aghayan",slug:"afshin-aghayan",fullName:"Afshin Aghayan"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10110",title:"Advances and Technologies in Building Construction and Structural Analysis",subtitle:null,isOpenForSubmission:!0,hash:"df2ad14bc5588577e8bf0b7ebcdafd9d",slug:null,bookSignature:"Dr. Ali Kaboli and Dr. Sara Shirowzhan",coverURL:"https://cdn.intechopen.com/books/images_new/10110.jpg",editedByType:null,editors:[{id:"309192",title:"Dr.",name:"Ali",middleName:null,surname:"Kaboli",slug:"ali-kaboli",fullName:"Ali Kaboli"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10175",title:"Ethics in Emerging Technologies",subtitle:null,isOpenForSubmission:!0,hash:"9c92da249676e35e2f7476182aa94e84",slug:null,bookSignature:"Prof. Ali Hessami",coverURL:"https://cdn.intechopen.com/books/images_new/10175.jpg",editedByType:null,editors:[{id:"108303",title:"Prof.",name:"Ali",middleName:null,surname:"Hessami",slug:"ali-hessami",fullName:"Ali Hessami"}],productType:{id:"1",chapterContentType:"chapter"}}],offset:8,limit:8,total:16},humansInSpaceProgram:{},teamHumansInSpaceProgram:{},route:{name:"chapter.detail",path:"/books/earthquake-engineering/seismic-risk-of-structures-and-the-economic-issues-of-earthquakes",hash:"",query:{},params:{book:"earthquake-engineering",chapter:"seismic-risk-of-structures-and-the-economic-issues-of-earthquakes"},fullPath:"/books/earthquake-engineering/seismic-risk-of-structures-and-the-economic-issues-of-earthquakes",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()