IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\n
By listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
All three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n
"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n
"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\n
In conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n
“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\n
We invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\n
Feel free to share this news on social media and help us mark this memorable moment!
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\n
By listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
All three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n
"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n
"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\n
In conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n
“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\n
We invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\n
Feel free to share this news on social media and help us mark this memorable moment!
\n\n
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"244",leadTitle:null,fullTitle:"Glaucoma - Current Clinical and Research Aspects",title:"Glaucoma",subtitle:"Current Clinical and Research Aspects",reviewType:"peer-reviewed",abstract:"This book summarizes current literature about research and clinical science in glaucoma and it is a synopsis and translation of the research conducted by individuals who are known in each of their respective areas. The book is divided into two broad sections: basic science and clinical science. The basic science section examines bench- and animal-modeling research in an attempt to understand the pathogenesis of glaucoma. The clinical science section addresses various diagnostic issues and the medical, laser and surgical techniques used in glaucoma management.",isbn:null,printIsbn:"978-953-307-263-0",pdfIsbn:"978-953-51-6558-3",doi:"10.5772/662",price:139,priceEur:155,priceUsd:179,slug:"glaucoma-current-clinical-and-research-aspects",numberOfPages:390,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"10a8059264775c2b4b6b9fcd49e61ba5",bookSignature:"Pinakin Gunvant",publishedDate:"November 9th 2011",coverURL:"https://cdn.intechopen.com/books/images_new/244.jpg",numberOfDownloads:56932,numberOfWosCitations:13,numberOfCrossrefCitations:9,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:23,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:45,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 25th 2010",dateEndSecondStepPublish:"November 22nd 2010",dateEndThirdStepPublish:"March 29th 2011",dateEndFourthStepPublish:"April 28th 2011",dateEndFifthStepPublish:"June 27th 2011",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"220127",title:"Dr.",name:"Pinakin",middleName:null,surname:"Davey",slug:"pinakin-davey",fullName:"Pinakin Davey",profilePictureURL:"https://mts.intechopen.com/storage/users/220127/images/system/220127.jpg",biography:"Dr. Pinakin Davey is a tenured Professor and Director of Research at Western University of Health Sciences, College of Optometry. He holds Doctor of Optometry (OD) degree from Southern College of Optometry and a Ph.D. from Anglia Ruskin University in Cambridge, England, in the area of glaucoma. His post-doctoral research fellowship at University of Louisville was focused on improving imaging techniques in glaucoma. He has authored over 50 international publications, and has given over 200 conference and invited presentations both nationally and internationally. 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1. Introduction
Models for actual dynamical processes are based on some restrictions. These restrictions are represented as a conservation law.
The conservation law states that a particular measurable property of an isolated dynamical system does not change as the system evolves over time.
Actual dynamical systems are open, and they are subject to strong external disturbances that violate the laws of conservation for the given system.
Conventionally, deterministic dynamical systems have an invariant function. Doobko1 V. in [1] proved that stochastic dynamical systems have an invariant function as well. For dynamical system which are described using a system of stochastic differential Itô equations, a first integral – or an invariant function, exists with probability 1 [2, 3, 4, 5, 6, 7, 8, 9, 10].
When we know only a conservation law for a dynamical system, and equations which describing this system are unknown, the invariant functions are a good tool for determination of these equations.
Our method differs for other (see, for example, [11]) preliminary in the fact that we construct a system of differential equation with the given first integral under arbitrary initial conditions. Besides, this algorithm is realized as software and it allows us to choose a set of functions for simulation. Moreover, we can construct both a system of stochastic differential equations and a system of deterministic ones.
The goal of this chapter is representation of modern approach to describe of dynamical systems having a set of invariant functions.
This chapter is structured as follows. Firstly, we show that the invariant functions for stochastic systems exist. Then, the generalized Itô – Wentzell formula is represented. It is a differentiated rule for Jump-diffusion function under variables which solves the Jump-diffusion equations system. This rule is basic for the necessary and sufficient conditions for the stochastic first integral (or invariant function with probability 1) for the Jump-diffusion equations system. The next step is the construction of the differential equations system using the given invariant functions. It can be applied for stochastic and nonstochastic cases. The concept of PCP1 (Programmed control with Prob. 1) for stochastic dynamical systems is introduced. Finally, we show an application of the stochastic invariant theory for a transit from deterministic model with invariant to the same stochastic model. Several examples of application of this theory are given and confirmed by results of numerical calculations.
2. Notation and preliminaries
Now we introduce the main concepts which we will use below.
Let wt, t∈0∞ be a Wiener process or a (standard) Brownian motion, i. e.
w0=0,
it has stationary, independent increments,
for every t>0, wt has a normal N0t distribution,
it has continuous sample paths,
every trajectory of wt is not differentiated for all t≥0.
A νtA is called a Poisson random measure or standard Poisson measure (PM) if it is non-negative integer random variable with the Poisson distribution νtA∼PoitΠA, and it has the properties of measure:
νtA is a random variable for every t∈0T, A∈Rn′,
νtA∈N∪0, νt∅=0,
if A∩B=∅, then νtA∪B=νtA+νtB,
EνtA=tΠA,
if #A is a number of random events from set A during t, then
Pt#A=k=tΠAkk!exp−tΠA.
ν˜tA=νtA−EνtA is called a centered Poisson measure (CPM).
Let wt=w1t…wmt∗ be an m-dimensional Wiener process, such that the one-dimensional Wiener processes wkt for k=1,…,m is mutually independent.
Take a vector γ∈Θ with values in Rn′. Denote by νΔtΔγ the PM on 0T×Rn′ modeling independent random variables on disjoint intervals and sets. The Wiener processes wkt, k=1,…,m, and the Poisson measure ν0TA defined on the specified space are Ft-measurable and independent of one another.
Consider a random process xt with values in Rn, n≥2, defined by the Equation [12]:
dxt=Atdt+Btdwt+∫Rγgtγxνdtdγ,E1
where At=a1t…ant∗, Bt=bj,kt is n×k - matrix, and gtγ=g1tγ…gntγ∗∈Rn, and γ∈Rn′≕Rγ, while wt is an m-dimensional Wiener process. In general the coefficients At, Bt, and gtγ are random functions depending also on xt. Since the restrictions on these coefficients relate explicitly only to the variables t and γ, we use precisely this notation for the coefficients of (1) instead of writing Atxt, txt, and gtxtγ.
A system (1) is the stochastic differential Itô equation with Wiener and Poisson perturbations, which named below as a Jump-diffusion Itô equations system (GSDES).
We will consider the dynamical system described using ordinary deterministic differential equations (ODE) system and ordinary stochastic differential Itô equations (SDE) system of different types, taking into account the fact that x∈Rn, n≥2.
3. An existence of an invariant function (with Prob.1) for stochastic dynamical system under strong perturbations
Consider the diffusion Itô equation in R3 with orthogonal random action with respect to the vector of the solution
dvt=−μvtdt+b∣vt∣vt×dwt,E2
where v∈R3, w∈R3, and wit, i=1,2,3 are independent Wiener processes. This equation is a specific form of the Langevin equation.
V. Doobko in [1] showed that the system (2) have an invariant function called a first integral of this system:
utv=exp2μtv02−b2μ.
This, in particular, implies that
limt→∞vt2=b2μ,
i.e. process ∣vt∣ is a nonrandom function and the random process vt itself is generated in a sphere of constant radius bμ.
In [4, 5, 10] it is shown that invariant function exists for other stochastic equations of Langevin type. To obtain this result, it is necessary to use the Itô’s formula.
4. The generalized Itô – Wentzell formula for jump-diffusion function
The rules for constructing stochastic differentials, e.g., the change rule, are very important in the theory of stochastic random processes. These are Itô’s formula [13, 14] for the differential of a nonrandom function of a random process and the Itô – Wentzell2 formula [15] enabling us to construct the differential of a function which per se is a solution to a stochastic equation. Many articles address the derivation of these formulas for various classes of processes by extending Itô’s formula and the Itô – Wentzell formula to a larger class of functions.
The next level is to obtain a new formula for the generalized Itô Equation [14] which involves Wiener and Poisson components. In 2002, V. Doobko presented [7] a generalization of stochastic differentials of random functions satisfying GSDES with CPM based on expressions for the kernels of integral invariants (only the ideas of a possible proof) were sketched in [7]. The result is called” the generalized Itô – Wentzell formula”.
In contrast to [7], the generalized Itô – Wentzell formula for the noncentered Poisson measure was represented in [9, 16, 17]. The proof [9] of the generalized Itô – Wentzell formula uses the method of stochastic integral invariants and equations for their kernels. In this case the requirement on the character of the Poisson distribution is only a general restriction, as the knowledge of its explicit form is unnecessary. Other proofs in [16, 17] are based on traditional stochastic analysis and the use of approximations to random functions related to stochastic differential equations by averaging their values at each point.
The generalized Itô – Wentzell formula relying on the kernels of integral invariants [9] requires stricter conditions on the coefficients of all equations under consideration: the existence of second derivatives. The reason is that the kernels of invariants for differential equations exist under certain restrictions on the coefficients.
Since the random function Ftxt has representation as stochastic diffusion Itô equation with jumps, we can use the generalized Itô – Wentzell formula, proved by us by several methods in accordance with different conditions for the equations coefficients. Now we consider only one case.
We will use the following notation: Cys is the space of functions having continuous derivatives of order s with respect to y, C0sy is the space of bounded functions having bounded continuous derivatives of order s with respect to y.
Theorem 1.1 (generalized Itô – Wentzell formula). Consider the real function Ftx∈Ct,x1,2, tx∈0T×Rn with generalized stochastic differential of the form
dtFtx=Qtxdt+∑k=1mDktxdwkt+∫RγGtxγνdtdγE3
whose coefficients satisfy the conditions:
Qtx∈Ct,x1,2,Dktx∈Ct,x1,2,Gtxγ∈Ct,x,γ1,2,1.
If a random process xt obeys (1) and its coefficients satisfy the conditions
By analogy with the terminology proposed earlier, let us call formula (5) “the generalized Itô – Wentzell formula for the GSDES with PM” (GIWF).
By analogy with the classical Itô and Itô – Wentzell formulas, the generalized Itô – Wentzell formula is promising for various applications. In particular, it helped to obtain equations for the first and stochastic first integrals of the stochastic Itô system [9], equations for the density of stochastic dynamical invariants, Kolmogorov equations for the density of transition probabilities of random processes described by the generalized stochastic Itô differential Equation [8], as well as the construction of program controls with probability 1 for stochastic systems [18, 19].
5. A first integral for GSDES
In the theory of ODE, there are constructed equations to find deterministic functions, first integrals which preserve a constant value with any solutions to the equation. The concept of a first integral plays an important role in theoretical mechanics, for example, to solve inverse problems of mechanics or in constructing controls of dynamical systems.
It turned out that the first integral exists in the theory of stochastic differential equations (SDE) as well. However, there appears an additional classification connected with different interpretations. This gives a first integral for a system of SDE (see [1]), a first direct integral, and a first inverse integral for a system of Itô SDE (see [20]).
Definition 1.1 [1, 3]. Let xt be an n-dimensional random process satisfying a system of Itô SDE
dxit=ai(txt)dt+∑k=1mbik(txt)dwktx(tx0)t=0=x0,E6
whose coefficients satisfy the conditions of the existence and uniqueness of a solution [12]. A nonrandom function utx∈Ct,x1,2 is called a first integral of the system of SDE if it takes a constant value depending only on x0 on any trajectory solution to (6) with probability 1:
u(t,xtx0=u0x0almostsurely,
or, in other words, its stochastic differential is equal to zero: dtutxt=0.
Another important notion in the theory of deterministic dynamical systems is given by the notion of an integral invariant introduced by Poincaré [21].
As it turned out, there also exist integral invariants for stochastic dynamical systems [2, 3]. In [7] V. Doobko give the concept of a kernel (=density) of a stochastic integral invariant and, based on it, formulate the notion of a stochastic first integral and a first integral as a deterministic function for GSDES with the centered Poisson measure, which makes it possible to compose a list of first integrals for stochastic differential equations.
Consider a random process xt, x∈Rn, which is a solution to GSDES
whose coefficients (in general, random functions) satisfy the conditions of the existence and uniqueness of a solution [12] and the following smoothness conditions:
aitx∈Ct,x1,1,bijtx∈Ct,x1,2,gitxγ∈Ct,x,γ1,2,1.E8
Suppose that ρtxω is a random function connected with any deterministic function ftx∈S⊂C01,2tx by the relations
∫RnρtxωftxdΓ̂x=∫Rnρ0yftxtydΓ̂yE9
∫Rnρ0xdΓ̂x=1,E10
lim∣x∣→∞ρ0xω=lim∣x∣→∞ρ0x=0,dΓ̂x=∏i=1ndxi,E11
where y≔x0, and xty is a solution to (7), and ω is a random event.
i.e., for the random function ρtxω, there exists a nonrandom functional preserving a constant value:
∫RnρtxωdΓ̂x=1.E13
Then, with conditions (10) and (11), Eq. (9) can be regarded as a stochastic integral invariant, and the function (t, x) can be viewed as its density.
Definition 1.2 [3]. A nonnegative random function ρtxω is referred to as a stochastic kernel or the stochastic density of a stochastic integral invariant (of nth order) if conditions (9), (10), and (11) are held.
Note that a substantial difference which made it possible to consider the invariance of the random volume on the basis of a kernel of an integral operator in [3, 7], is that (9) contains a functional factor. Thus, the notion of a kernel of an integral invariant [3] for a system of ordinary differential equations can be regarded as a particular case by taking ftx=1 and excluding from (7) the randomness determined by the Wiener and Poisson processes.
Using the GIWF (5), we obtain equation for the stochastic kernel function [9].
This result plays a major role in obtaining of equation for the stochastic first integral.
6. Necessary and sufficient conditions for the stochastic first integral
Lemma 1.1. If ρtxω is a stochastic kernel of an integral invariant of n th order of a stochastic process xt starting from a point x0 then, for every t, it satisfies the equality
ρtxtx0ωJtx0ω=ρ0x0,
where Jtx0ω is the Jacobian of transition from xt to x0.
Definition 1.3 A set of kernels of integral invariants of nth order is called complete if any other function that is the kernel of this integral invariant can be presented as a function of the elements of this set.
In [9] it is shown that a system of GSDE (7) whose coefficients satisfy the conditions in (8), has a complete set of kernels consisting of n+1 functions.
Suppose that ρltxω≠0, l=1,…,m, m≤n+1 are kernels of the integral invariant (9). Lemma 1.1 implies that, for any l≠n+1, the ratio ρltxtyωρn+1txtyω is a constant depending only on the initial condition x0=y for every solution xt to the GSDE (7) because
ρstxtyωρn+1txtyω=ρs0yρn+10y.E15
Since for some realization ω1 we have
utxtx0≡ρltxtx0ω1ρstxtx0ω1=ρl0x0ρs0x0≡u0x0,
and it means, that dtutxt=0.
Definition 1.4 A random function utxω defined on the same probability space as a solution to (7) is referred to as a stochastic first integral of the system (7) of Itô ˆ GSDE with NCM if the following condition holds with probability 1:
utxtx0ω=u0x0almostsurely
for every solution xtx0ω to (7).
For practical purposes, for example, to construct program controls for a dynamical system under strong random perturbations, the presence of a concrete realization is important, i.e., the parameter ω is absent in what follows. In this connection, we introduce one more notion.
Definition 1.5 A nonrandom function utx is called a first integral of the system of GSDE (7) if it preserves a constant value with probability 1 for every realization of a random process xt that is a solution to this system:
utxtx0=u0x0almostsurely.
Thus, a stochastic first integral includes all trajectories (or realizations) of the random process while the first integral is related to one realization.
Construct an equation for utxω using the relation
lnustxω=lnρstxω−lnρltxω,E16
as a result of assertion (15). Let us differentiate lnρtx (omit ω) using generalized Itô – Wentzell formula:
where d˜tρtx is the right side of Eq.(14) without the integral expression. Having written down the equations for lnρstx and lnρltx, and taking into account this result and Eq.(16), we obtain:
which means that a stochastic first integral utxω of the Itô generalized Eq. (7) is a solution to the GSDE (18).
For a first integral which is a nonrandom function of one realization, the differential is also defined by an equation of the form of (18).
Theorem 1.2 Let xt be a solution to the GSDES (7) with conditions (8). A nonrandom function utx∈Ct,x1,2 is a first integral of system (7) if and only if it satisfies the conditions:
∂utx∂t+∂utx∂xiaitx−12bjk(tx)∂biktx∂xj=0,
biktx∂utx∂xi=0, for all k=1,m¯,
utx−utx+gtxγ=0 for any γ∈Rγ in the entire domain of definition of the process.
Theorem (6) allows us to obtain a method for construction of differential equations systems on the basis of the given set of invariant functions.
7. Construction of the differential equations system using the given invariant functions
The concept of a first integral for a system of stochastic differential equations plays a key role in our theory. In this section, we will use a set of first integrals for the construction of a system of differential equations.
Theorem 1.3 [22]. Let Xt be a solution of the Eq. (19) and let a nonrandom function stx be continuous together with its first-order partial derivatives with respect to all its variables. Assume the set e→oe→1…e→n defines an orthogonal basis in R+×Rn. If function stx is a first integral for the system (19), then the coefficients of Eq. (19) and the function stx together are related by the conditions:
1. Functions Bktx=∑i=1nbiktxe→ik=1…m, which determine columns of the matrix Btx, belong to a set
3. Coefficient ΘtXγ=∑i=1nγitxγe→i, related to Poisson measure, is defined by the representation Θtxγ=ytxγ−x, where ytxγ is a solution of the differential equations system
This solution satisfies the initial condition: ytxγγ=0=x.
The arbitrary functions fij=fijtx, hij=hijtx, and φij=φijty⋅γ are defined by the equalities fijtx=∂fitx∂xj, hijtx=∂hitx∂xj, and φijty⋅γ=∂φity⋅γ∂yj. Sets of functions φity⋅γ and the function gtx together form a class of independent functions.
Using this theorem, we can to construct SDE system of different types and ODE system. Choice of arbitrary functions allows us to construct a set of differential equations systems with the given invariant functions. Theorem (7) allows us to introduce a concept of Programmed control with probability 1 for stochastic dynamical system.
8. Programmed control with Prob. 1 for stochastic dynamical systems
Definition 1.6 [18, 19]. A PCP1 is called a control of stochastic system which allows the preservation with probability 1 of a constant value for the same function which depends on this systems position for time periods of any length T.
Let us consider the stochastic nonlinear jump of diffusion equations system:
where P⋅, Z⋅ are given matrix functions and B⋅, L⋅ are the functions that may either be known or not. For such systems we construct a unit of programmed control utXtKtXtMtXt which allows the system (24) to be on the given manifold u(tXt)=u0x0 with Prob. 1 (PCP1) for each t∈0T, T≤∞.
Suppose that the nonrandom function stXt is the first integral for the same stochastic dynamical system. The PCP1 utXtKtXtMtXt is the solution for the algebraic system of linear equations.
Theorem 1.4 Let a controlled dynamical system be subjected to Brownian perturbations and Poisson jumps. The unit of PCP1 utXtKtXtMtXt, allowing this system to remain with probability 1 on the dynamically structured integral mfd stXtxoω=s0xo, is a solution of the linear equations system (with respect to functions utxt), KtXt, MtXt which consists of Eq. (19) and Eq. (24). The coefficients of the Eq. (19), (and the coefficients of the Eq. (24) respectively) are determined by the theorem 7. The response to the random action is defined completely.
We show how the stochastic invariants theory can be applied to solve different tasks.
9. Stochastic models with invariant function which are based on deterministic model with invariant one
In this section we consider a few examples for application of the theory above to modeling actual random processes with invariants [23]. Firstly, we consider an example of construction of a differential equation system with the given invariant. Secondly, we study a general scheme for the PCP1 determination. And finally, we show the possibility of construction of stochastic analogues for classical models described by a differential equations system with an invariant function. The suggested method of stochastization is based on both the concept of the first integral for a stochastic differentialItô equations system (SDE) and the theorem for construction of the SDE system using its first integral.
9.1 Construction of a differential equations system
It is necessary to construct a differential equations system for X∈R3, t≥0 such that the equality
Xt−Y12t+Y2t+et=0E25
is satisfied with Prob.1. The equality (25) means that the differential equations system has a first integral stXtY1tY2t=Xt−Y12t+Y2t+et with initial condition 0,1,0∗:
We choose the functions q00⋅, fi⋅ and hi⋅, i=1,2,3, in accordance with the restriction of the task and taking into account the utility for modeling.
9.2 Transit from deterministic model with invariant to the same stochastic model
Now we describe a general scheme for application of the theory above.
The suggested method of stochastization is based on both the concept of the first integral for a stochastic differentialItô equations system (SDE) and the theorem for construction of the SDE system using its first integral.
Let us consider a classical model
dy1t=F1tytdt,dy2t=F2tytdt,dy3t=F3tytdt,E28
with an invariant uty.
Then we construct the GSDE system, taking into account the equality utxt=u0x0=C:
Finally, we have constructed stochastic analogue for classical model described by a differential equations system and having an invariant function.
9.3 The SIR (susceptible-infected-recovered) model
The SIR is a simple mathematical model of epidemic [24], which divides the (fixed) population of N individuals into three” compartments” which may vary as a function of time t.
St are those susceptible but not yet infected with the disease,
It is the number of infectious individuals,
Rt are those individuals who have recovered from the disease and now have immunity to it,
the parameter λ describes the effective contact rate of the disease,
the parameter μ is the mean recovery rate.
The SIR model describes the change in the population of each of these compartments in terms of two parameters:
Suppose that the function utxyz=x+y+z−N is a first integral, vtxyz=2e−t+x and htxyz=y are complementary functions, and qtxyz=x is arbitrary function. The initial condition is: x0=1, y0=0, z0=0. Then constructed differential equations system has the form
Let us simulate a numerical solution of Eg.(36), where N=1 (for example). Figure 1 shows simulation for system without jumps, the Figure 2 shows the processes with jumps.
Figure 1.
Numerical solution for Eq.(36) without jumps.
Figure 2.
Numerical solution for Eq.(36) with jumps.
In such a way we could use the system of differential equations
as initial step for construction of stochastic SIR-model. A good choice of complementary functions vtxyz and htxyz allows us to obtain such coefficients that ensure that the solution xtytzt of the differential equations system satisfy some reasonable limitations.
9.4 The predator–prey model
The Lotka - Volterra equations or the predator–prey equations used to describe the dynamics of biological systems in which two species interact, one as a predator and the other as prey.
The Lotka - Volterra model makes a number of assumptions, not necessarily realizable in nature, about the environment and evolution of the predator and prey populations:
The prey population finds ample food at all times.
The food supply of the predator population depends entirely on the size of the prey population.
The rate of change of population is proportional to its size.
During the process, the environment does not change in favor of one species, and genetic adaptation is inconsequential.
Predators have limitless appetite.
Let us note: N1t is the number of prey, and N2t is the number of some predator, ε1, ε2, η1 and η2 are positive real parameters describing the interaction of the two species.
The populations change through time according to the pair of equations:
Let us assume that ε1=2, ε2=1, η1=η2=1, and C=1, and initial condition is x0=y0=1. The function utxy=x−1ex−y2e−2y is a first integral, htxy=y−x+e−t and qtxy=x are complementary functions.
We cannot find an analytical solution of the differential equations system
where AtNt, BtNt, CtNt, DtNt, EtNt are determined by Eq.(43).
Figures 3 and 4 show two realizations for numerical solution of Eq. (44).
Figure 3.
Numerical simulation 1 for solution of Eq.(44).
Figure 4.
Numerical simulation 2 for solution of Eq.(44).
Another examples of a differential equation system construction and models see in [25, 26, 27, 28, 29].
10. Conclusion
The invariant method widens horizons for constructing and researching into mathematical models of real systems with the invariants that hold out under any strong random disturbances.
\n',keywords:"Itô equation, Poisson jump, invariant function, differential equations system construction, stochastic system with invariants, programmed control with probability 1",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/75359.pdf",chapterXML:"https://mts.intechopen.com/source/xml/75359.xml",downloadPdfUrl:"/chapter/pdf-download/75359",previewPdfUrl:"/chapter/pdf-preview/75359",totalDownloads:285,totalViews:0,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:0,impactScore:0,impactScorePercentile:46,impactScoreQuartile:2,hasAltmetrics:0,dateSubmitted:"November 2nd 2020",dateReviewed:"January 27th 2021",datePrePublished:"February 23rd 2021",datePublished:"July 28th 2021",dateFinished:"February 23rd 2021",readingETA:"0",abstract:"In this chapter we consider the invariant method for stochastic system with strong perturbations, and its application to many different tasks related to dynamical systems with invariants. This theory allows constructing the mathematical model (deterministic and stochastic) of actual process if it has invariant functions. These models have a kind of jump-diffusion equations system (stochastic differential Itô equations with a Wiener and a Poisson paths). We show that an invariant function (with probability 1) for stochastic dynamical system under strong perturbations exists. We consider a programmed control with Prob. 1 for stochastic dynamical systems – PSP1. We study the construction of stochastic models with invariant function based on deterministic model with invariant one and show the results of numerical simulation. The concept of a first integral for stochastic differential equation Itô introduce by V. Doobko, and the generalized Itô – Wentzell formula for jump-diffusion function proved us, play the key role for this research.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/75359",risUrl:"/chapter/ris/75359",book:{id:"10471",slug:"advances-in-dynamical-systems-theory-models-algorithms-and-applications"},signatures:"Elena Karachanskaya",authors:[{id:"338070",title:"Associate Prof.",name:"Elena",middleName:null,surname:"Karachanskaya",fullName:"Elena Karachanskaya",slug:"elena-karachanskaya",email:"elena_chal@mail.ru",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Notation and preliminaries",level:"1"},{id:"sec_3",title:"3. An existence of an invariant function (with Prob.1) for stochastic dynamical system under strong perturbations",level:"1"},{id:"sec_4",title:"4. The generalized Itô – Wentzell formula for jump-diffusion function",level:"1"},{id:"sec_5",title:"5. A first integral for GSDES",level:"1"},{id:"sec_6",title:"6. Necessary and sufficient conditions for the stochastic first integral",level:"1"},{id:"sec_7",title:"7. Construction of the differential equations system using the given invariant functions",level:"1"},{id:"sec_8",title:"8. Programmed control with Prob. 1 for stochastic dynamical systems",level:"1"},{id:"sec_9",title:"9. Stochastic models with invariant function which are based on deterministic model with invariant one",level:"1"},{id:"sec_9_2",title:"9.1 Construction of a differential equations system",level:"2"},{id:"sec_10_2",title:"9.2 Transit from deterministic model with invariant to the same stochastic model",level:"2"},{id:"sec_11_2",title:"9.3 The SIR (susceptible-infected-recovered) model",level:"2"},{id:"sec_12_2",title:"9.4 The predator–prey model",level:"2"},{id:"sec_14",title:"10. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Dubko V. A. First Integrals of Systems of Stochastic Differenial Equations. Preprint. 1978. Izd-vo An USSR, In-t Matematiki, Kiev. [in Russian], https://ru.calameo.com/read/003168372f1f76b3dbbbc [Accessed: 08 January 2021]'},{id:"B2",body:'Dubko V. A. Integral invariants for some class of systems of stochastic differential equations. Dokl. Akad. Nauk Ukr. SSR, Ser. A. 1984, 18(1) : 17–20. [In Ukranian]'},{id:"B3",body:'Dubko V. A. Questions in the Theory and Applications of Stochastic Differential Equations. DVO AN SSSR, Vladivostok, 1989. [in Russian]'},{id:"B4",body:'Dubko V. A. and Chalykh E. V. Construction of an analytic solution for one class of equations of the Langevin type with orthogonal random actions. Ukr. Mat. Zh. 1998, 50(4) : 666–668. https://doi.org/10.1007/BF02487397'},{id:"B5",body:'Chalykh E. On one generalization of the Langevin equation with determinate modulus of velocity. Ukr. Mat. 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Automation and Remote Control. 2009, 70(8) : 1364–1375. https://link.springer.com/article/10.1134/S0005117909080098 [Accessed: 08 January 2021]'},{id:"B26",body:'Karachanskaya E. and Tagirova T. Construction of stochastic transport models with a constant function. IOP Conference Series Earth and Environmental Science. December 2019, 403, no. 012211. https://iopscience.iop.org/article/10.1088/1755-1315/403/1/012211 [Accessed: 08 January 2021]'},{id:"B27",body:'Karachanskaya E. V. and Petrova A. P. Modeling of the programmed control with probability 1 for some financial tasks. Mathematical notes of NEFU. 2018, 25(1): 25–37. [In Russin] https://doi.org/10.25587/SVFU.2018.1.12766 [Accessed: 08 January 2021]'},{id:"B28",body:'Averina T., Karachanskaya E., and Rybakov K. Statistical modeling of random processes with invariants. International Multi-Conference on Engineering, Computer and Information Sciences (SIBIRCON). Novosibirsk. 2017 : 34–37. https://ieeexplore.ieee.org/document/8109832 [Accessed: 08 January 2021]'},{id:"B29",body:'Averina T. A., Karachanskaya E. V., and Rybakov K. A. Statistical analysis of diffusion systems with invariants. Russian Journal of Numerical Analysis and Math. Modelling. 2018, 33(1) : 1–13. https://doi.org/10.1515/rnam-2018-0001 [Accessed: 08 January 2021]'}],footnotes:[{id:"fn1",explanation:"Different variant of transliteration of the name: Dubko"},{id:"fn2",explanation:"Different variants of transliteration of this formula name: Itô – Wentcell, Itô – Venttcel’, Itô – Ventzell."}],contributors:[{corresp:"yes",contributorFullName:"Elena Karachanskaya",address:"elena_chal@mail.ru",affiliation:'
Far-Eastern State Transport University, Khabarovsk, Russia
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1. Introduction
Bladder cancer is the most common malignant tumor involving the urinary tract. Histologically, bladder cancers can be urothelial carcinomas, squamous cell carcinomas and adenocarcinomas, out of which urothelial carcinomas constitute over 90% [1]. Urothelial carcinoma is derived from the specialized epithelia of the bladder wall. Using a well-established differentiation program, basal stem cells at the stromal interface self-renew and generate intermediate and superficial urothelial cells to maintain and regenerate the urothelium in response to daily wear and tear. Bladder cancer results from the deregulation of this program. Conventionally, bladder cancer can be divided into non-muscle invasive bladder cancer (NMIBCs) and muscle invasive bladder cancers (MIBCs), based on the invasion of the muscularis propria. The low grade superficial NMIBCs and high grade MIBCs (HG MIBCs) develop along divergent molecular pathways of tumorigenesis and also show diverse biological behavior and molecular profile. Low grade NMIBCs constitute the majority of newly diagnosed bladder cancer cases, typically have a long protracted clinical course characterized by multiple recurrences, and require life-long monitoring, significantly contributing to bladder cancer morbidity. On the other hand, a large proportion of the MIBCs eventually metastasize, contributing to the bulk of bladder cancer mortality [2, 3].
Low grade papillary urothelial carcinomas occur due to fibroblast growth factor receptor 3 (FGFR3)/RAS/RAF pathway alterations, while the HG MIBCs develop along the TP53/RB1 mutation pathway [4, 5]. Chromosome 9 deletion occurs in the early phase of bladder cancer tumorigenesis. FGFR3/HRAS mutations frequently occur during the development of hyperplasia and low grade (Ta) carcinoma. Hyperplasia develops into high grade urothelial carcinoma (Ta) through the acquisition of CDKN2A alterations, which may progress to become T1 carcinoma after additional TP53/RB1 inactivation. TP53 mutations frequently occur during the development of urothelial dysplasia. These may develop into carcinoma in situ (Tis) after RB1 inactivation, which then progresses through non-muscle invasive infiltrating urothelial carcinomas (T1) to muscle invasive (T2) carcinoma.
Traditional classifications for bladder cancer are mainly based on pathological features and tumor stage. However, even with similar pathological staging and grading, recurrence and progression of bladder cancer shows marked heterogeneity, and directly affects optimal monitoring and treatment response. Only a proportion of cases of bladder cancer of a given grade and stage will progress to a higher stage. Thus the same treatment, such as, transurethral resection alone, or the administration of BCG or neoadjuvant chemotherapy may not be adequate for others. Some tumors are less likely to metastasise and need only local resection, while others are highly invasive and need radical cystectomy and/or other treatments. Currently, there is still no effective means to distinguish between the two. The pathological features of the tumor cannot fully reflect the “intrinsic characteristics” of bladder cancer.
With the rapid development of sequencing, mass spectrometry and other techniques, studies based on the ‘-omics’ technology has transformed our understanding of human cancers. The basic method involves cataloging the entire mRNA expression pattern and DNA alteration profile by sequencing, microarray and other technologies and then performing a cluster analysis of the different genes based on gene expression levels and genes involved in a given biological process. After performing hierarchical cluster analysis on mRNA expression profiling data, clusters were validated by DNA PCR and/or immunohistochemistry (IHC), DNA methylation profiling, miRNA or lncRNA analysis. Among the earliest applications of this approach was to define intrinsic molecular subtypes in human breast cancer by Perou et al., [6]. Subsequently, over the last decade, molecular subtypes with distinct clinical behavior, histology and response to treatment were identified in other malignancies e.g. colon cancer, gliomas, acute leukemias and so on. Molecular subtype profiling was applied only recently in bladder cancer, with the earliest attempts dating back to 2010. Several different molecular classification systems have emerged since, with four standing out in the MIBCs, developed by Lund University group [7, 8, 9, 10], The Cancer Genome Atlas (TCGA) consortium [11, 12], MD Anderson Cancer Centre [13] and the University of North Carolina [14]. Several other studies have followed up, in an attempt to unify [15] and reach a consensus [16] between the classification systems. Although each group defended the existence of a different numbers of subtypes (n = 2–6), there was remarkable overall concordance among the groups (Table 1). At the highest level, all classification systems recognized the existence of intrinsic luminal and non-luminal (basal) subtypes, which resembled normal luminal/intermediate and basal urothelial cells in gene expression profile.
Table showing overlap between the subtypes in the initial classification systems and the cardinal properties of these subtypes, adapted from McConkey et al. [17], CAF-cancer associated fibroblasts, EMT- epithelial-mesenchymal transition.
For the two major types of bladder cancer, NMIBC and MIBC, molecular subtyping of bladder cancer can be divided into early subtyping (which included both NMIBC and MIBC), NMIBC subtyping and MIBC subtyping (Table 2).
Neural-like, luminal-like, papillary-like, HER2-like, squamous cell carcinoma-like and mesenchymal-like
Table 2.
Summary of major molecular subtyping systems, adapted from Zhu et al., 2020 [18].
2. Early bladder cancer subtyping systems
The earliest representative studies on the molecular classification of bladder cancer were conducted by Sjödahl et al. at the University of Lund, initially proposed in 2010 and finalized in 2012 and the tumor differentiation classification by Chan et al., of the Baylor University group, 2012 [19]. The Baylor classification focused on tumor biology. They proposed a KRT14/Thy-1/CD44 expressing cancer stem cells as the bladder cancer precursor. This cancer stem cell evolved into a partially differentiated KRT5/KRT17/CD44-positive progeny, which in turn acquired KRT8/18 expression and eventually differentiated into luminal cells expressing uroplakins and KRT20. Tumors were classified into basal, intermediate and differentiated classes based on their resemblance to normal urothelial differentiation. Based on the above classification, the KRT14 group (basal subtype) showed the poorest prognosis and were also found to be resistant to neoadjuvant cisplatin-based chemotherapy.
The Lund University group initially defined two intrinsic molecular subtypes named as MS1 and MS2 based on gene expression, genomic, and gene mutation levels by whole genome comparative genomic hybridization and mutation studies [7]. By combining molecular and pathologic data, it was possible to divide tumors into grade 1 or 2 (MS1) and grade 3 (MS2) (WHO1999), and into Ta (MS1) and ≥ T2 (MS2) stages based on the MS1 and MS2 subtypes.
Subsequently, an extensive biological interpretation of gene expression data identified that biological themes including immune, late cell cycle, keratin, receptor tyrosine kinases and FGFR3 signatures determined their data structure. Based on tumor histopathology, gene signatures, and status of FGFR3, PIK3CA, and TP53 mutations, three major subtypes of UC were defined: urobasal (Uro) (further subdivided into MS1a, MS1b, and MS2b2.1), genomically unstable (GU) (MS2a1 and MS2a2), and SCC-like (SCCL) (MS2b2.2) [8]. Subsequent studies also identified an “infiltrated” group in which the stromal inflammatory transcripts were prominently expressed. Among the urobasal tumors (MS2b2.1), a subset showed “progressed phenotype” with aberrant expression of basal keratins in suprabasal cell layers and upregulation of late cell cycle activity. These tumors were mostly large and invasive, and were named urobasal B to distinguish it from urobasal A tumors that were non-muscle invasive in almost all cases. The molecular subtypes thus defined, transcended pathological staging and all four subtypes (UroA, UroB, GU, and SCCL) were detected among T1 tumors. The initial Lund taxonomic studies included both NMIBC and MIBC and subsequent studies focussed predominantly on MIBC classification.
3. Molecular subtyping of early-stage bladder cancer
Variability in terminology has created a challenge in the molecular classification of early-stage bladder cancer. Treating clinicians emphasize the dichotomous division of BCs into NMIBC and MIBC, and often lump all NMIBCs together when planning molecular studies. In contrast pathologists tend to see a stark difference between non-invasive tumors and invasive tumors limited to the lamina propria and classify accordingly.
Molecular diversity in non-invasive BC differs from that of MIBC. Non-invasive BC histologically includes papillary UC and flat CIS, although both may co-exist in the same patient. As we have discussed earlier, low-grade non-invasive papillary UC has a high frequency of FGFR3 mutation. LGUC progresses to HGUC and invasive carcinoma through the acquisition of TP53 mutations and 9p21 loss involving the gene encoding CDKN2A. In contrast, most CIS lesions have TP53 mutations early in evolution and do not acquire FGFR3 mutations [4, 5].
In the Lund system [8], majority of non-invasive UCs are urothelial-like, while CIS may be either urothelial-like or genomically unstable. They identified a “CIS signature” by utilizing a 16-gene classifier which was specifically expressed in flat CIS, as well as in early-stage invasive carcinoma with associated CIS, and a large proportion of MIBCs of the basal-squamous subtype. In addition, MIBCs with concurrent CIS had greater genomic instability compared with those without it. Although majority of non-invasive papillary UCs were of luminal subtype, there is substantial molecular diversity among cases. The most clinically relevant diversity was related to cell cycle regulatory genes. Tumors with greater activation of the cell cycle had higher rates of recurrence and progression to MIBCs.
The UROMOL study of 2016 [20] evaluated expression profiles of NMIBCs including non-invasive papillary UC and invasive UC limited to the lamina propria (stage T1). A few cases of CIS and a small group of MIBCs were also included for comparison. Tumors were classified into 3 subtypes based on relative expression of luminal and basal-squamous markers and cell cycle activity. Three subtypes were proposed, named as Type 1 (early cell cycle activation and higher luminal gene expression), Type 3 (early cell cycle activation with lower luminal gene expression) and Type 2 (late cell cycle activation). Type 2 tumors, which included the highest proportion of T1 samples, had the greatest propensity to progress to muscle invasion. On the other hand, expression of luminal genes did not significantly affect patient outcome. In addition, non-invasive papillary tumors also varied in the degree of chromosomal instability. The unstable group had tumors with higher proliferation, greater mutational burden, and high-grade histology.
Von Kessel et al., in 2018 [21], determined that methylation status of GATA2, TBX2, TBX3 and ZIC4 and mutations in FGFR3, TERT, PIK3CA, and RAS correlated with progression rates of NMIBC. Wild-type FGFR3 and GATA2 and TBX3 methylation were significantly correlated with NMIBC progression. Thus, high risk NMIBC group was reclassified into good, moderate and poor prognostic classes with low, medium and high risk of progression.
However, because molecular subtyping of non–muscle-invasive bladder cancer has not demonstrated clear value in clinical decision making, it is not currently recommended to incorporate it on a routine basis, as per the ISUP recommendations published in 2020.
4. Molecular subtyping of MIBC
Much of the work on molecular subtyping of bladder cancer has been undertaken with MIBCs in consideration and an increasing number of classification systems have emerged with four of them standing out (Figure 1). Although the subtypes within these systems are largely similar, they differ in clinically and biologically meaningful ways.
Figure 1.
Figure showing the similarities between the molecular subtypes in the different classification systems. Luminal and basal subtypes exist in all classification systems (figure adapted from Zhu et al. [18]).
The UNC classification proposed by Damrauer et al. [14], used K2 consensus clustering, to divide tumors into basal (KRT5/6 and CD44) vs. luminal (PPARG, GATA3, KRT20, and UPK2) subtypes utilizing a 47 gene classifier, BASE47. The basal subtype showed similarities with the basal subtype of breast cancers, as demonstrated by applying the PAM50 signature to their dataset. In addition, like in breast cancers, a claudin-low subgroup was identified among basal tumors. The claudin-low subgroup had outcomes similar to basal tumors and was rich in epithelial-mesenchymal transition (EMT) signatures and tumor initiating cell markers. A significant enrichment in genes related to inflammatory cell infiltration and immune checkpoint was also seen in the basal subgroup and, more specifically, among the claudin-low tumors. There was no significant difference in TP53 pathway alterations in the subtypes. The basal subtype, which was more frequent among females, had a high rate of RB pathway gene alterations, while the luminal subtype was rich in FGFR3 and TSC1mutations.
The MDA group [13] also classified BC into basal, p53-like and luminal tumors similar to breast cancer. Their luminal and p53-like subtypes had similar mRNA profiles but wild-type p53 gene was significantly activated in the p53-like subtype. All three subtypes had similar frequency of p53 mutations, but the p53-ness contributed by increased wild-type p53 expression was thought to contribute to chemo-resistance in the p53-subtype. The basal subtype was enriched in squamous cell differentiation markers and activated p63 and was more invasive with poorer clinical prognosis.
The TCGA 2014 [12] subtyped MIBCs into four clusters numbered I to IV utilizing an integrated genomic analysis of chemotherapy-naive, invasive UCs by analyzing for somatic mutations, DNA copy number alterations, mRNA and microRNA expression profile, as well as protein analysis, and DNA methylation studies. Cluster I predominantly exhibited papilloma phenotype and was enriched in FGFR3 mutations. Both cluster I and II expressed GATA3, FOXA1, UPK3A transcription factors and uroplakin family of genes and were enriched in RBB2 mutations and ER beta. Cluster III expressed squamoid phenotype and its associated keratin expression. Subsequently in 2017, TCGA expanded their classification [11] into five distinct subtypes, diving luminal tumors into three subtypes, luminal papillary, luminal and luminal infiltrated. They also included a neural subtype in addition to the earlier described basal subtype.
4.1 Intrinsic molecular subtypes and intra-tumor heterogeneity
Intrinsic molecular subtype, a term which first used in breast carcinomas [6] refers to subtypes which reflect an intrinsic property of the tumor. The luminal and basal intrinsic subtypes reflect the property of the tumor cells to show urothelial or basal stem-cell-like differentiation signatures [23].
However, transcriptomic studies identified the entire genetic signature of a tumor, which in the case of invasive malignancies, included variable components of stromal and immune signatures. Thus, in addition to the two intrinsic subtypes, some of the subtypes defined in the various study groups were based on the characteristics of the tumor-stroma or tumor infiltrating inflammatory cells such as the p53-like‘subtype [13], infiltrated subtype [8], luminal-infiltrated subtype [11] as examples. These non-intrinsic subtypes could be recognized as a property of the stroma or inflammatory cells when studies were performed later which localized the gene expression patterns in situ, by immunohistochemistry [10, 23, 24]. Many of these non-intrinsic subtypes could be resolved into luminal and basal subtypes based on tumor phenotype on immunohistochemistry, while others continued to express non-luminal, non-basal phenotype, like the double negative subtype of Dadhania et al., [24].
4.1.1 Intrinsic luminal subtype
At the top of the hierarchical level, MIBCs were divided into luminal-like and nonluminal-like classes based on the presence or absence of bimodally expressed urothelial differentiation signature.
About half of the MIBCs expressed this signature characterized by the expression of KRT20, UPK1–3 (uroplakin 1, 2 and 3), epithelial biomarkers (E-cadherin/CDH1 and members of the miR-200 family), along with transcriptional regulators PPARG (peroxisome proliferator activated receptor-γ), GRHL2–3 (grainyhead like transcription factor), ELF3 and TBX2–3. Luminal MIBCs also displayed active Estrogen Receptor/TRIM24 pathway gene expression and were enriched with FOXA1, GATA3, ERBB2 and ERBB3 expressed on superficial (umbrella cells) and intermediate cells of the normal urothelium [7]. There was increased expression of fibroblast growth factor receptor-3 (FGFR3), with activating FGFR3 mutations in the most differentiated luminal tumors.
The luminal tumors were further sub-stratified into urothelial-like (UroA, UroB and UroC) and genomically unstable (GU) subtypes by the Lund University group [8], luminal papillary, luminal and luminal infiltrated subtypes by TCGA [11] and luminal papillary, luminal non-specified, and luminal unstable subtypes in the Consensus classification [16].
The urothelial-like tumors expressed FGFR3 and CCND1, and frequently showed 9p21 (CDKN2A) loss. On immunohistochemistry, only the urothelial-like tumors retained the basal stratification seen in normal urothelium and express CK5 at least focally, particularly at the tumor-stroma interface [9, 10]. Similar to UroA tumors in the Lund classification, the luminal-papillary subtype in TCGA and Consensus classification were also characterized by FGFR3 mutations; by papillary histology; and by low carcinoma-in-situ scores. Such cancers had a low risk for progression, and while preliminary data suggests a low likelihood of response to cisplatin-based NACT [25], they may respond to tyrosine kinase inhibitors of FGFR3 family [26, 27] or to PPARγ-inhibitors [10] or to Estrogen receptor modulators [28].
Genomically unstable subtype (GU) of luminal tumors expressed FOXM1 and absent to low levels of FGFR3, but not KRT5 [9]. They also frequently showed RB1 loss, and had a high rate of TP53 mutations. Highest ERBB2 expression is also seen in GU subtype. Although they showed urothelial differentiation signature, GU tumors were in fact poorly differentiated and frequently high grade on histology [9, 10]. On immunohistochemistry, they did not express CK5, but expressed late cell cycle makers such as p16 [10]. The luminal unstable subtype of Consensus classification showed similar features to the GU subtype described by Lund University group. These tumors may respond to drugs targeting ERBB2 [23].
In terms of prognosis, luminal papillary tumors or UroA tumors had very good prognosis, while the GU subtype showed an intermediate prognosis compared to urothelial-like and basal/SCC-like tumors [10, 12, 16].
4.1.2 Intrinsic non-luminal subtype: Basal and neuronal
Intrinsic non-luminal MIBC included basal MIBC (Choi et al., 2014) [13] and neuronal or small cell neuroendocrine MIBC. The basal subtype has been renamed basal-squamous in the later classification systems as it is characterized by squamous differentiation [8, 12].
Basal-squamous MIBCs expressed signal biomarkers similar to normal basal cells in the urothelium like high molecular weight cytokeratins KRT1, KRT5, KRT6, KRT14, KRT16, 15 KRT6A, KRT6B, KRT6C and CD44 and CDH3 [8, 11]. However, unlike normal basal urothelial cells which retained urothelial differentiation factors (GATA3 and PPARG), the basal-squamous subtype showed down-regulation of this signature. Interestingly, they had a higher incidence in females unlike all the other subtypes which were male predominant [11].
Basal MIBCs were also characterized by up-regulation of the epidermal growth factor receptor (EGFR) and other ligands of the epidermal differentiation complex such as S100A7 and SPRR1B, similar to basal breast and head and neck squamous cell carcinomas. Cell cycle regulator p63 played a central role in controlling the basal pathway of differentiation, and STAT3, NFκB, and Hypoxia Induced Factor-1α (HIF-1α) were also involved [23].
Without treatment, basal MIBCs had poorer survival [13, 14] but they responded well to neoadjuvant chemotherapy [11]. Because NACT pathological complete response is associated with excellent long-term survival, aggressive early management of basal MIBCs with NACT offers the best chance for improved survival for these patients.
This subtype also had the strongest immune expression signature, including T cell markers, inflammation genes and lymphocytic infiltrates. It is predicted that the basal-squamous subtype may respond to anti-PD-L1, anti-PD-1 and anti-CTLA-4 agents [28, 29]. EGFR-, NFκB, HIF-1α/VEGF, and/or STAT3-targeted agents may also have a role within this subtype [27].
The neuronal subtype showed no histopathological distinction from other types of MIBC in most cases. Nonetheless, they had high levels of TP53 and RB1 mutations, similar to small cell carcinomas in other tissues. It had the worst survival of the mRNA expression subtypes, making it important to recognize [10, 11].
P53-like MIBCs showed some overlap in gene expression with luminal and basal subtypes of the UNC classification but were characterized by the expression of an active wild-type p53-associated gene expression signature [13]. P53-like subtype of bladder cancer responded poorly to neo-adjuvant chemotherapy [13, 28, 30]. Wild-type p53-induced reversible senescence and quiescence had been implicated in causing chemo-resistance. However, even though p53-associated expression signatures were present, TP53 mutation frequencies were found to be similar in luminal, p53-like and basal subtypes defined by Choi et al., (2014). The p53-ness as measured by mRNA expression was found to be a more accurate predictor of de novo and induced MIBC chemo-resistance than analysis of TP53 mutational status [23].
The luminal-infiltrated subtype reported by the TCGA was characterized by low tumor purity, with high expression of epithelial-mesenchymal transition (EMT) and myofibroblast markers, and of the miR-200 s. It showed medium expression of PD-L1 and CTLA4 immune markers. This subtype had been reported to respond to immune checkpoint inhibitors like Anti-PD-L1 [29].
Stromal-like subtype from the Consensus classification, the infiltrated subtype from the Lund classification [10] and claudin-low subtype of the MD Anderson Cancer Centre classification [14] all showed similar features of low-tumor purity, high EMT and stromal related transcripts with increased cancer stem cell-like gene expression profile. Claudin-low tumors described by Damrauer et al. [14], in addition, showed increased expression of claudins-1, 3, and 7 and had a similar expression profile to the claudin-low breast cancer subtype. Dadhania et al., [24] in their meta-analysis of the TCGA, Lund and MD Anderson cohorts also identified a subset of tumors with low urothelial and basal expression signatures, which they termed “double negative”, which showed similar expression profile to claudin-low tumors.
With tumor progression, alterations are seen both in the intrinsic characteristics of the tumor cell, as well as in the tumor microenvironment (TME). Early MIBC molecular classification systems mainly focused on the molecular classification of tumor cells themselves. With a deeper understanding of BC cells and their TME, molecular subtyping efforts have begun to focus more on intratumor heterogeneity, stromal-extracellular matrix (ECM) interactions and immune cell infiltration, allowing further refinement of the molecular subtypes. Currently, studies on molecular subtyping are mainly based on whole tumor DNA or RNA studies rather than focusing on a single tumor cell. In this method, intratumoral heterogeneity can greatly affect the accuracy of molecular subtyping. Warrick et al. [31] conducted a pathological examination on 309 bladder cancer markers and found that nearly one fourth of them exhibited intratumoral variation in tissue samples. Out of the 83 specimens subtyped by them with the Lund subtyping system, 39% exhibited molecular heterogeneity. Even among the subtypes, the basal-squamous subtype particularly showed the greatest variability; with approximately 78% of these tumors simultaneously exhibiting the genomically unstable or urothelial-like subtype.
Several immunohistochemistry based algorithms have been developed in an attempt to classify bladder cancer into clinically and prognostically significant molecular subtypes [9, 10, 24, 32]. The use of immunohistochemistry as a surrogate to molecular testing shows promise in making molecular subtyping amenable to widespread use. The use of a simple panel comprising of a luminal urothelial markers like GATA3 and basal keratin marker like KRT5 can help identify a GATA3 positive, KRT5 low luminal subtype and a GATA3 negative, KRT5 high basal subtype. Tumors which are negative for GATA3 and have low keratin may be further tested for mesenchymal or neuroendocrine markers. The luminal tumors may also be further subtyped into uro-like tumors which are p16 negative and genomically unstable tumors which show p16 positivity [33]. The subtypes thus identified have demonstrated significant prognostic and predictive value [24, 32].
5. Clinical significance of molecular subtypes of bladder cancer
Not only do clinical outcomes differ among the molecular subtypes, but also therapeutic response. The gold-standard for management of MIBCs for disease confined to the pelvis includes radical cystectomy preceded by platinum based neoadjuvant chemotherapy. Although a significant minority of patients treated this way achieves durable response and improved cancer specific survival, a sizeable fraction does not respond. In fact, a meta-analysis has suggested that there is only 5% absolute survival benefit at 5 years for patients treated in this manner [34]. In addition, concerns regarding delayed surgery and risk of serious morbidity have limited the usage rates of NACT for cystectomy patients at 25% or less [35, 36]. Biomarker tests that predict chemo-response could address these problems by identifying patients most likely to benefit. In this regard, data suggests that NAC confers the greatest benefit in basal tumors [11, 29], while the “p53-like subtype” has been reported to confer chemo-resistance [13]. However, current ISUP working group guidelines of 2020 do not recommend routine subtyping to guide NACT [37].
Data published by the TCGA Consortium stated that about 69% of BCs contain potentially actionable therapeutic targets which associate with specific molecular subtypes [11]. Mutations and amplifications of FGFR3 are seen in 50–80% of superficial bladder cancers and up to 20% of MIBCs [19]. Luminal-papillary tumors demonstrate a high rate of these alterations [11]; however, clinical trials have not yet incorporated molecular classification to determine patient eligibility. Similarly PIK3CA is also a frequently mutant gene and therapies targeting PI3K pathway have also shown preclinical BC trials [38]. Other targets such as ERBB2 and TSC1 are also being investigated as therapeutic targets.
Molecular subtyping may also provide a guide to BC immunotherapy. Anti-programmed death 1 (PD-1) and anti-programmed death-ligand 1(PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) are important second line therapies for MIBC with NAC failure. A few are also approved as first line therapy for cisplatin ineligible cases. Unfortunately, not all patients benefit from immunotherapy [39, 40]. Testing for biomarkers of response involves IHC for PD-1 or PD-L1 or estimation of tumor mutation burden, micro-satellite instability or immune-microenvironment of the tumor. However, none of these biomarkers have shown overwhelming predictive efficacy over others [41, 42, 43]. The luminal infiltrated subtype in the TCGA 2017 subtyping system was found to be enriched in PD-L1, CTLA-4 and other immune signatures. In particular, although this subtype did not respond well to NACT, they showed good response to anti-PD-L1 and anti-PD-1 treatment. The basal subtype has also shown response to immunotherapeutic agents in addition to being sensitive to NACT [11, 29]. Molecular subtypes may thus help define patient selection for immunotherapy.
6. Conclusion
Compared to traditional classification of BCs, molecular subtypes provide more information regarding tumor biology, prognosis and treatment. In general, BC can be divided into luminal and non-luminal subtypes based on their degree of urothelial differentiation. The luminal subtype is further subdivided into those with papillary features, which are superficial, predominantly non-invasive. Though they carry good prognosis when compared to other treatment-naïve subtypes, they do not respond well to conventional NAC and may benefit from targeted therapies. The luminal infiltrated type has more inflammatory and stromal signatures. They are more invasive than luminal papillary tumors and may respond well to immunotherapies. Basal/squamous tumors express stem cell and squamous differentiation associated gene expression signatures. They are aggressive untreated, but respond well to NACT as well as immunotherapies but are insensitive to radiotherapy. The neural subtype forms a minority of non-luminal tumors with neuronal or neuroendocrine phenotype and usually carry poor prognosis but respond to NACT. There are an increasing number of molecular subtyping systems being constantly updated. While they carry great potential to reform BC prognostication and therapeutics, they are not entirely without limitations. Accessibility is a key issue in the present times. Molecular subtyping is mainly based on “static” research, especially in NMIBC, and enables a one-time detection and analysis of tumor specimens rather than “dynamic” tracking to over the disease course. It has also mainly focused on genome and transcriptome research so far but proteomics and immune status of tumors are also closely related to their development. Therefore, the implementation of multiomics is a key necessity in future studies on molecular subtyping. Intra-tumor heterogeneity also provides another challenge with patient outcome being dominated by one subtype more than the other. With the rapid development of single-cell high-throughput sequencing, mass spectrometric analysis, immune cell analysis and other technologies, the accuracy of the molecular subtyping prediction system need further improvement. Compared to the existing classification system, molecular subtyping methods offer a more comprehensive analysis, particularly to guide adjuvant chemotherapy, targeted therapy and immunotherapy. In the future, these classifications will become an important complementary approach to traditional pathological classification.
Conflict of interest
The authors declare no conflict of interest.
\n',keywords:"molecular classification, muscle invasive bladder cancer, taxonomy, transcriptomics, targeted therapy",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/77332.pdf",chapterXML:"https://mts.intechopen.com/source/xml/77332.xml",downloadPdfUrl:"/chapter/pdf-download/77332",previewPdfUrl:"/chapter/pdf-preview/77332",totalDownloads:171,totalViews:0,totalCrossrefCites:0,dateSubmitted:"March 1st 2021",dateReviewed:"March 24th 2021",datePrePublished:"June 25th 2021",datePublished:"November 24th 2021",dateFinished:"June 25th 2021",readingETA:"0",abstract:"Bladder cancer is a biologically and clinically heterogeneous disease. Traditional classification systems, based on pathologic grade, stage and clinical prognosis fail to fully explain how tumors with similar pathology exhibit diverse biological behavior. The introduction of transcriptomics technology has allowed us to catalog all of the mRNA expression patterns and DNA alterations in a given tumor thus expanding our understanding of human cancers. Molecular subtype profiling was attempted only recently in bladder cancer, with the earliest attempts dating back to 2010. Several different molecular classification systems have emerged since. Some of these systems address early bladder cancer, while others focus exclusively on the life-threatening muscle invasive tumors. These molecular subtypes have distinct morphological and clinical characteristics with different therapeutic and prognostic implications, particularly in the era of targeted therapies and immunotherapy. However, molecular subtyping is not without its limitations. Despite the rapidly expanding evidence for important clinical implications, much work is still needed to establish the utility (or lack thereof) of molecular subtyping, and its application in daily practice.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/77332",risUrl:"/chapter/ris/77332",signatures:"Seema Kaushal and Hena Khandakar",book:{id:"10339",type:"book",title:"Modern Approach to Diagnosis and Treatment of Bladder Cancer",subtitle:null,fullTitle:"Modern Approach to Diagnosis and Treatment of Bladder Cancer",slug:"modern-approach-to-diagnosis-and-treatment-of-bladder-cancer",publishedDate:"November 24th 2021",bookSignature:"Francesco Ziglioli and Umberto Maestroni",coverURL:"https://cdn.intechopen.com/books/images_new/10339.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83969-191-1",printIsbn:"978-1-83969-190-4",pdfIsbn:"978-1-83969-192-8",isAvailableForWebshopOrdering:!0,editors:[{id:"62240",title:"Dr.",name:"Francesco",middleName:null,surname:"Ziglioli",slug:"francesco-ziglioli",fullName:"Francesco Ziglioli"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"338581",title:"Dr.",name:"Seema",middleName:null,surname:"Kaushal",fullName:"Seema Kaushal",slug:"seema-kaushal",email:"seema.dr@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"346918",title:"Dr.",name:"Hena",middleName:null,surname:"Khandakar",fullName:"Hena Khandakar",slug:"hena-khandakar",email:"henakhandakar@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"All India Institute of Medical Sciences",institutionURL:null,country:{name:"India"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Early bladder cancer subtyping systems",level:"1"},{id:"sec_3",title:"3. Molecular subtyping of early-stage bladder cancer",level:"1"},{id:"sec_4",title:"4. Molecular subtyping of MIBC",level:"1"},{id:"sec_4_2",title:"4.1 Intrinsic molecular subtypes and intra-tumor heterogeneity",level:"2"},{id:"sec_4_3",title:"4.1.1 Intrinsic luminal subtype",level:"3"},{id:"sec_5_3",title:"4.1.2 Intrinsic non-luminal subtype: Basal and neuronal",level:"3"},{id:"sec_6_3",title:"4.1.3 Non-intrinsic subtypes: P53-like, luminal-infiltrated, stromal-like, infiltrated, claudin-low",level:"3"},{id:"sec_9",title:"5. Clinical significance of molecular subtypes of bladder cancer",level:"1"},{id:"sec_10",title:"6. Conclusion",level:"1"},{id:"sec_14",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Holger Moch, Peter A. Humphrey, Thomas M. Ulbright, Victor E. 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Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
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IntechOpen’s Academic Editors and Authors have received funding for their work through many well-known funders, including: the European Commission, Bill and Melinda Gates Foundation, Wellcome Trust, Chinese Academy of Sciences, Natural Science Foundation of China (NSFC), CGIAR Consortium of International Agricultural Research Centers, National Institute of Health (NIH), National Science Foundation (NSF), National Aeronautics and Space Administration (NASA), National Institute of Standards and Technology (NIST), German Research Foundation (DFG), Research Councils United Kingdom (RCUK), Oswaldo Cruz Foundation, Austrian Science Fund (FWF), Foundation for Science and Technology (FCT), Australian Research Council (ARC).
Open Access publication costs can often be designated directly in the grants or in specific budgets allocated for that purpose. Many of the most important funding organisations encourage, and even request, that the projects they fund are made available at no cost to the wider public. IntechOpen strives to maintain excellent relationships with these funders and ensures compliance with mandates.
\\n\\n
In order to help Authors identify appropriate funding agencies and institutions, we have created a list, based on extensive research on various OA resources (including ROARMAP and SHERPA/JULIET) of organizations that have funds available. Before consulting our list we encourage you to petition your own institution or organization for Open Access funds or check the specifications of your grant with your funder to ascertain if publication costs are included. Where you are in receipt of a grant you should clarify:
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\\n\\t
Does your institution already have a budget for covering Open Access publication costs?
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\\n\\n
Please note that this list is not a definitive one and is updated regularly. To suggest possible modifications or the inclusion of your institution/funder, please contact us at funders@intechopen.com
\\n\\n
Please be aware that you must be a member, or grantee, of the institutions/funders listed in order to apply for their Open Access publication funds.
Open Access publication costs can often be designated directly in the grants or in specific budgets allocated for that purpose. Many of the most important funding organisations encourage, and even request, that the projects they fund are made available at no cost to the wider public. IntechOpen strives to maintain excellent relationships with these funders and ensures compliance with mandates.
\n\n
In order to help Authors identify appropriate funding agencies and institutions, we have created a list, based on extensive research on various OA resources (including ROARMAP and SHERPA/JULIET) of organizations that have funds available. Before consulting our list we encourage you to petition your own institution or organization for Open Access funds or check the specifications of your grant with your funder to ascertain if publication costs are included. Where you are in receipt of a grant you should clarify:
\n\n
\n\t
Does your institution already have a budget for covering Open Access publication costs?
\n\t
Does your grant list Open Access publication fees as legitimate direct/indirect costs?
\n
\n\n
If you are associated with any of the institutions in our list below, you can apply to receive OA publication funds by following the instructions provided in the links. Please consult the Open Access policies or grant Terms and Conditions of any institution with which you are linked to explore ways to cover your publication costs (also accessible by clicking on the link in their title).
\n\n
Please note that this list is not a definitive one and is updated regularly. To suggest possible modifications or the inclusion of your institution/funder, please contact us at funders@intechopen.com
\n\n
Please be aware that you must be a member, or grantee, of the institutions/funders listed in order to apply for their Open Access publication funds.
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This book chapter is prepared to evaluate the effects of occupational risks on health and decrease the exposure to occupational risks of health professionals by searching national and international literatüre. Thus, awareness can be raised to define occupational risks and help planning services for health professionals. American National Institute for Occupational Safety and Health (NIOSH) has reported 29 kinds of physical, 25 kinds of chemical, biological 24 varieties, 10 and six kinds of ergonomic and psycho‐social hazards and risks. According to ILO, it has been reported that there is 1.25 trillion dollars loss each year due to the OHS problems. In Turkey, the loss of only social security systems has been reported as approximately 4 million Turkish Liras per year. Health professionals have work stress, and they suffer from the inconvenient design and the hazards within the workplace. The health of the health professionals affects the health of the community. Thus, it is important to decrease the exposure to occupational risks of health professionals and diligently work on this issue.",book:{id:"5528",slug:"occupational-health",title:"Occupational Health",fullTitle:"Occupational Health"},signatures:"Nilgun Ulutasdemir and Ferdi Tanir",authors:[{id:"191796",title:"Associate Prof.",name:"Nilgun",middleName:null,surname:"Ulutasdemir",slug:"nilgun-ulutasdemir",fullName:"Nilgun Ulutasdemir"},{id:"195566",title:"Prof.",name:"Ferdi",middleName:null,surname:"Tanır",slug:"ferdi-tanir",fullName:"Ferdi Tanır"}]},{id:"52610",doi:"10.5772/65687",title:"Working in Cold Environment: Clothing and Thermophysiological Comfort",slug:"working-in-cold-environment-clothing-and-thermophysiological-comfort",totalDownloads:1783,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"The chapter presents an in-depth discussion over the occupational activities in a cold environment, which can be performed both outdoors and indoors. It explores the differences between working in natural and artificial cold environment. The thermophysiological comfort, the reactions of the thermoregulatory system during cold exposure, and cold-related injuries are presented and discussed in detail. Clothing as the only insulating barrier between the body and the cold environment is discussed, and hi-tech solutions for development of cold protective clothing are presented. The particular application of standards for the indoor environment is presented, and their input for the proper management of the occupational activities in the cold is analyzed.",book:{id:"5528",slug:"occupational-health",title:"Occupational Health",fullTitle:"Occupational Health"},signatures:"Radostina A. Angelova",authors:[{id:"175795",title:"Associate Prof.",name:"Radostina",middleName:"A.",surname:"Angelova",slug:"radostina-angelova",fullName:"Radostina Angelova"}]},{id:"53519",doi:"10.5772/66479",title:"Understanding the Stakeholders as a Success Factor for Effective Occupational Health Care",slug:"understanding-the-stakeholders-as-a-success-factor-for-effective-occupational-health-care",totalDownloads:2550,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"Effective occupational health care at the workplace requires collaboration, partnerships and alliances with internal, interface and external stakeholders. Essential steps for solid work with various stakeholders are identification of key stakeholders, systematic analysis of their views and positions, and development of stakeholder participation and involvement. Stakeholder analysis aims to evaluate and understand stakeholders from the perspective of an organization. Stakeholder analysis starts with identifying and classifying the key stakeholders. After their identification, questions are asked about their position, interest, influence, inter-relations, networks and other characteristics of stakeholders, with reference to their past and present positions, and future potential. The results are presented as stakeholder maps as well as by the power-interest matrix of the stakeholders. Stakeholder analysis serves an organization and its various actors as a guideline in identifying, planning and implementing strategies for managing stakeholder relationships and utilizing the full potential of various stakeholders in developing occupational health care.",book:{id:"5528",slug:"occupational-health",title:"Occupational Health",fullTitle:"Occupational Health"},signatures:"Ari-Matti Auvinen",authors:[{id:"193252",title:"M.A.",name:"Ari-Matti",middleName:null,surname:"Auvinen",slug:"ari-matti-auvinen",fullName:"Ari-Matti Auvinen"}]},{id:"52842",doi:"10.5772/66120",title:"Gene-Environment Interactions: The Case of Asbestosis",slug:"gene-environment-interactions-the-case-of-asbestosis",totalDownloads:1386,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"It is becoming evident that both environmental/lifestyle and genetic factors may influence the development of many diseases. This chapter highlights the importance of considering gene-environment interactions, which is shown on the example of our studies into asbestosis, one of the most frequent asbestos-related diseases. Asbestos fibres induce generation of reactive oxygen and nitric species (ROS and RNS), and it is generally accepted that ROS and RNS are involved in the pathogenesis of asbestos-related diseases. Human tissues contain specific enzymes that metabolise ROS and RNS, such as superoxide dismutases (SODs), catalase (CAT), glutathione-S-transferases (GSTs) and inducible nitric oxide synthase (iNOS). As these enzymes are encoded by polymorphic genes, genetic variability in an individual’s capacity to detoxify these reactive species may modify the risk for disease. Our previous studies into asbestosis showed that the associations between the risk of asbestosis and MnSOD Ala-9Val polymorphism and between asbestosis and iNOS genotypes were modified by CAT −262C>T polymorphism. A strong interaction was also found between smoking (lifestyle factor) and GSTM1-null polymorphism, between smoking and iNOS (CCTTT)n polymorphism and between cumulative asbestos exposure (environmental factor) and iNOS (CCTTT)n polymorphism. The findings of our studies and other studies indicate that in addition to environmental and/or occupational exposure to different hazards and lifestyle factors, genetic factors as well as the interactions between different genotypes, between genotypes and lifestyle factors and between genotypes and environmental/occupational exposure to hazards may also have an important role on the development of diseases and should be further investigated.",book:{id:"5528",slug:"occupational-health",title:"Occupational Health",fullTitle:"Occupational Health"},signatures:"Vita Dolzan, Metoda Dodic-Fikfak and Alenka Franko",authors:[{id:"60449",title:"Prof.",name:"Vita",middleName:null,surname:"Dolžan",slug:"vita-dolzan",fullName:"Vita Dolžan"},{id:"195632",title:"Prof.",name:"Alenka",middleName:null,surname:"Franko",slug:"alenka-franko",fullName:"Alenka Franko"},{id:"195633",title:"Prof.",name:"Metoda",middleName:null,surname:"Dodic-Fikfak",slug:"metoda-dodic-fikfak",fullName:"Metoda Dodic-Fikfak"}]},{id:"53365",doi:"10.5772/66480",title:"Ibuprofen as a Treatment for Work-Related Musculoskeletal Disorders: Effectiveness versus Caveats",slug:"ibuprofen-as-a-treatment-for-work-related-musculoskeletal-disorders-effectiveness-versus-caveats",totalDownloads:1682,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Work-related upper limb disorders (WMSDs), also known as repetitive strain injuries, affect a large subsection of the US population. These disorders are a significant source of injury, morbidity, loss of work, and pain. We have developed a rat model of upper extremity repetitive work at high forces, and observed exposure-dependent increased inflammatory responses in all tissues involved in performing the task. A 2- to 8-week regimen of oral ibuprofen provided to rats while they continued to perform a high-repetition high-force task ameliorated these inflammatory responses as well as several motor declines. Ibuprofen treatment also attenuated task-induced tissue fibrosis, cartilage degeneration, and bone osteopenia, indicating their link to inflammatory processes. However, ibuprofen did not significantly attenuate persistent nocifensive pain behaviors (reflexive grip strength results are presented) likely because of persistent increases in inflammatory cytokines in the spinal cord, suggestive of central sensitization. Since long-term ibuprofen use can induce a number of negative side effects, such as gastritis, multi-pronged approaches should be considered with anti-inflammatory drugs included for only short time periods.",book:{id:"5528",slug:"occupational-health",title:"Occupational Health",fullTitle:"Occupational Health"},signatures:"Mary F. Barbe and Ann E. Barr-Gillespsie",authors:[{id:"197229",title:"Dr.",name:"Mary F",middleName:null,surname:"Barbe",slug:"mary-f-barbe",fullName:"Mary F Barbe"},{id:"197459",title:"Dr.",name:"Ann",middleName:"E",surname:"Barr-Gillespie",slug:"ann-barr-gillespie",fullName:"Ann Barr-Gillespie"}]}],mostDownloadedChaptersLast30Days:[{id:"53716",title:"Occupational Risks of Health Professionals",slug:"occupational-risks-of-health-professionals",totalDownloads:2580,totalCrossrefCites:4,totalDimensionsCites:7,abstract:"Health service is an important work area which can lead to important risks related to occupational health and safety (OHS) of employees. This book chapter is prepared to evaluate the effects of occupational risks on health and decrease the exposure to occupational risks of health professionals by searching national and international literatüre. Thus, awareness can be raised to define occupational risks and help planning services for health professionals. American National Institute for Occupational Safety and Health (NIOSH) has reported 29 kinds of physical, 25 kinds of chemical, biological 24 varieties, 10 and six kinds of ergonomic and psycho‐social hazards and risks. According to ILO, it has been reported that there is 1.25 trillion dollars loss each year due to the OHS problems. In Turkey, the loss of only social security systems has been reported as approximately 4 million Turkish Liras per year. Health professionals have work stress, and they suffer from the inconvenient design and the hazards within the workplace. The health of the health professionals affects the health of the community. Thus, it is important to decrease the exposure to occupational risks of health professionals and diligently work on this issue.",book:{id:"5528",slug:"occupational-health",title:"Occupational Health",fullTitle:"Occupational Health"},signatures:"Nilgun Ulutasdemir and Ferdi Tanir",authors:[{id:"191796",title:"Associate Prof.",name:"Nilgun",middleName:null,surname:"Ulutasdemir",slug:"nilgun-ulutasdemir",fullName:"Nilgun Ulutasdemir"},{id:"195566",title:"Prof.",name:"Ferdi",middleName:null,surname:"Tanır",slug:"ferdi-tanir",fullName:"Ferdi Tanır"}]},{id:"53383",title:"New Paradigms in Ergonomics: The Positive Ergonomics",slug:"new-paradigms-in-ergonomics-the-positive-ergonomics",totalDownloads:2170,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"This chapter aims look at ergonomics from a positive point of view. According to International Ergonomics Association, ergonomics is “the scientific discipline concerned with the understanding of interactions among humans and other elements of a system, and the profession that applies theory, principles, data and methods to design in order to optimize human well-being and overall system performance”. The major types of ergonomics. Some of them are physical, cognitive, and positive ergonomics. Positive ergonomics: Positive ergonomics refers to a new type of ergonomics that stresses the positive aspects of the man-machine system. Its major interest is to make “human-machine system” enjoyable where the human feels pleasant. Emotional ergonomics: Similar to positive ergonomics, emotional ergonomics refers to a type of ergonomics that pays attention to the emotional aspects of the man-machine system. Spiritual ergonomics: Spiritual ergonomics is based on the idea that spirit is a key factor which determines the employee’s health and success in the man machine system, no matter what he/she is doing in that system. New approach to Occupational health: When considering the legacy of occupational health, we find that two approaches were adopted throughout of its history. These are: professional harmonization and ergonomics approaches.",book:{id:"5528",slug:"occupational-health",title:"Occupational Health",fullTitle:"Occupational Health"},signatures:"Mohamed Mokdad and Tawfik Abdel-Moniem",authors:[{id:"104865",title:"Prof.",name:"Mohamed",middleName:null,surname:"Mokdad",slug:"mohamed-mokdad",fullName:"Mohamed Mokdad"},{id:"194579",title:"Prof.",name:"Tawfik",middleName:null,surname:"Abdel Moniem",slug:"tawfik-abdel-moniem",fullName:"Tawfik Abdel Moniem"}]},{id:"53519",title:"Understanding the Stakeholders as a Success Factor for Effective Occupational Health Care",slug:"understanding-the-stakeholders-as-a-success-factor-for-effective-occupational-health-care",totalDownloads:2550,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"Effective occupational health care at the workplace requires collaboration, partnerships and alliances with internal, interface and external stakeholders. Essential steps for solid work with various stakeholders are identification of key stakeholders, systematic analysis of their views and positions, and development of stakeholder participation and involvement. Stakeholder analysis aims to evaluate and understand stakeholders from the perspective of an organization. Stakeholder analysis starts with identifying and classifying the key stakeholders. After their identification, questions are asked about their position, interest, influence, inter-relations, networks and other characteristics of stakeholders, with reference to their past and present positions, and future potential. The results are presented as stakeholder maps as well as by the power-interest matrix of the stakeholders. Stakeholder analysis serves an organization and its various actors as a guideline in identifying, planning and implementing strategies for managing stakeholder relationships and utilizing the full potential of various stakeholders in developing occupational health care.",book:{id:"5528",slug:"occupational-health",title:"Occupational Health",fullTitle:"Occupational Health"},signatures:"Ari-Matti Auvinen",authors:[{id:"193252",title:"M.A.",name:"Ari-Matti",middleName:null,surname:"Auvinen",slug:"ari-matti-auvinen",fullName:"Ari-Matti Auvinen"}]},{id:"52643",title:"Health‐Promoting Leadership Culture and its Role in Workplace Health Promotion",slug:"health-promoting-leadership-culture-and-its-role-in-workplace-health-promotion",totalDownloads:1804,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Purpose: The law on health and safety at work was implemented in Slovenia in 2011. On this basis, Slovenian organizations started preparation and implementation of workplace health promotion (WHP) programs. The article reports on research of the Slovenian leaders’ leadership style concerning their employees’ health following the new legislation.",book:{id:"5528",slug:"occupational-health",title:"Occupational Health",fullTitle:"Occupational Health"},signatures:"Simona Šarotar Žižek, Matjaž Mulej and Vesna Čančer",authors:[{id:"192730",title:"Associate Prof.",name:"Simona",middleName:null,surname:"Šarotar Žižek",slug:"simona-sarotar-zizek",fullName:"Simona Šarotar Žižek"}]},{id:"53481",title:"HSE Management for a Sound Work Environment: Strategies for Improving Health Safety and Environmental Indicators through Ergonomic Design Thinking",slug:"hse-management-for-a-sound-work-environment-strategies-for-improving-health-safety-and-environmental",totalDownloads:1670,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Ergonomic Design Thinking (EDT) is a project management methodology that takes advantage of two important concepts or themes in carrying out project actions. 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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. 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She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. 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