\r\n\tRisk management aims to develop an efficient organizational development environment through risk planning, assessment, analysis, and control. This process will apply in all areas of activity, and the evaluation framework is the same regardless of the field. This volume will aim to appeal to chapters that address methods, models, evaluation frameworks, benefits, barriers, and other dimensions of risk management. \r\n\tSustainability and the circular economy are approaches approached by many companies and have become activities of global interest. Protecting the environment, streamlining the consumption of organizational resources, reducing the amount of waste generated, and other activities are objectives of these efforts. The circular economy contributes to the sustainable development of the company or country and the achievement of the global objectives of sustainable development. This book will aim to collect various studies for organizational and global sustainability. \r\n\tLeadership has become a globally desirable approach that can help improve organizational competitiveness and reduce organizational risks. Risks and barriers in risk-free management can be well managed through effective organizational leadership. This book will aim to bring together chapters that explore different areas of leadership.
",isbn:"978-1-83768-218-8",printIsbn:"978-1-83769-991-9",pdfIsbn:"978-1-83768-219-5",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"5d9c14d51cb7e214a9093c454eab1404",bookSignature:"Prof. Larisa Ivascu, Dr. Ben-Oni Ardelean and Dr. Muddassar Sarfraz",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11937.jpg",keywords:"Technical Risk, Occupational Risk, Operational Risk Management, Economic Risk, Financial Risk, Thematic Mapping, Global Sustainability, Sustainability Models, Life Cycle Assessment, Critical Raw Materials, Global Leadership, Risks",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 5th 2022",dateEndSecondStepPublish:"June 2nd 2022",dateEndThirdStepPublish:"August 1st 2022",dateEndFourthStepPublish:"October 20th 2022",dateEndFifthStepPublish:"December 19th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"a month",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Dr. Ivascu obtained Ph.D. in Management and graduated with an MBA in Production and Transportation from the Faculty of Management, Politehnica University of Timisoara. She is the president of the scientific committee of the Academy of Political Leadership and vice-president of the Society for Ergonomics and Work Environment Management. Dr. Ivascu has been involved in national and international projects and has published nine books, and contributed scientifically to more than 200 scientific articles.",coeditorOneBiosketch:"Dr. Ben-Oni Ardelean obtained Ph.D. in Political Science and Ph.D. in Theology; he has extensive academic and political experience. He is the author of several books and numerous academic articles. He is highly preoccupied with supporting those in need, helping others to help themselves, and motivating people to live a life of purpose, love, and compassion. Dr. Ardelean is also a researcher dedicated to the management area and an honorary member of the Academy of the Romanian Scientists.",coeditorTwoBiosketch:"Dr. Muddassar Sarfraz completed a postdoctoral fellowship in Business Management at the Business School of Hohai University, China. He is a member of the British Academy of Management, Chinese Economists Society (USA), World Economic Association (UK), and the American Economic Association. He is an ambassador of the MBA program at Chongqing University, China. 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He completed a postdoctoral fellowship in Business Management at the Business School of Hohai University, China. He has published numerous papers in foreign authoritative journals and academic conferences at home and abroad. He is senior editor of Cogent Business & Management, associate editor of Frontiers in Psychology, Energies, and Future Business Journal, and guest editor of Frontiers in Environmental Sciences and INQUIRY. He is a member of the British Academy of Management, Chinese Economists Society (USA), World Economic Association (UK), and the American Economic Association, and an ambassador of the MBA program at Chongqing University, China. 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1. Introduction
Numerous studies on high-transition temperature (Tc) superconductivity were motivated primarily by the intention to explore the nature of cuprates. Experimental results, particularly those based on hard X-ray absorption spectra, show that Cu ions reveal a mixed valence and are accountable for high-Tc superconductivity. Recently discovered iron-based superconductors with perovskite blocking layers [i.e., LnFeAsO (Ln = lanthanide), BaFe2As2, KFeAs, FeSe, and FeAs] have received considerable attention similar to cuprate superconductivity, which was first explored in the 1980s. New superconducting compounds and non-cuprate superconductors with magnetic elements, particularly 3d transition metals, have been widely analyzed by various scholars. Spinel LiTi2O4 (LTO) is a titanium (Ti)-based superconductor that is considered an exotic BCS s-wave superconductor with a Tc of ~12 K [21]. This superconductor is regarded as such because it can be described using electron–phonon interaction within the framework of the BCS model [43]. Of the more than 200 typical compounds with an AB2O4 normal spinel structure, in which low-valent-state cation “A” occupies the tetrahedral (8a, Td) interstitial sites and high-valent-state cation “B” occupies the octahedral (16d, Oh) sites, only a few exhibit superconductivity, including CuV2S4 (Tc = 4.5 K), CuRhS4 (Tc = 4.8 K), and CuRhSe4 (Tc = 3.5 K). LTO is the only known spinel oxide superconductor, and it has the highest Tc among superconductors with a spinel structure. The 3d transition metals occupying the Oh sites in spinel oxides may generally exhibit antiferromagnetism, ferromagnetism, and charge/orbital ordering. The nature of magnetic and electronic properties depends on the average valence of the cations. The closely related case of LiV2O4 (LVO), which is an isostructural compound, exhibits distinct physical properties. LVO is the closest neighbor to LTO, and it contains a mixed-valence system with an equal ratio of V3+ (S = 1) and V4+ (S = ½). LVO exhibits strong electronic correlation, resulting in a greatly enhanced effective mass. The resistivity of this compound displays a metallic character. Although LVO is not a superconductor, it exhibits a heavy fermionic behavior typically observed in a Ce-based (4f electron) system [2, 22].
Similar to cuprates [6, 33] and pnictides [9, 24], Ti-based superconductors (titanate) present the possibility of a mixed-valence state (with electronic configuration of 3d0.5, equal ratio of Ti3+ of spin S = 1/2 and Ti4+ with S = 0) in the ground state. Given that magnetic impurities can suppress the superconductivity of various materials, an investigation into whether the dilute doping of magnetic ions in LTO results in the complete suppression of superconductivity must be conducted. Such an undertaking may provide valuable insights into the mechanism of superconductivity. A previous research observed a rapidly suppressed superconducting Tc in magnetically doped system LiTi1-xMxO4 (M = Cr and V) [19]. Among the explored dopants, vanadium (V) was determined to be more effective in decreasing Tc even at small proportions, and it was also observed in other 3d transition metals (e.g., Cr, Mn, Fe, etc.). The results of the study not only signified the magnetic influences and other mechanisms for Tc suppression, but also the charge density wave and structural distortion. For V-doped LTO, the Tc of LTO decreases with V at 2% proportion from ~13 K to ~5 K [18, 19, 24, 49]. These superconducting activities in such a series may unravel the mechanism of superconductivity. Material study on the atomic/electronic structure has essentially illuminated the understanding of its electron transportation properties. Studies have investigated the electronic structure of LTO [8, 39]. The decrease in superconductivity of V-doped LTO is discussed based on a pair-breaking mechanism [19] and a crystalline distortion from octahedral symmetry [34]. The change of Ti and V valence states is suggested to be thoroughly linked to their chemical and physical properties. Electron–electron interaction cannot be overlooked because magnetic ions occupy the structures [32]. In this event, the mechanism of superconductivity remains unknown.
The atomic and electronic structures of the novel spinel LTO superconductors have been investigated. X-ray spectroscopy, X-ray absorption near-edge structure (XANES) spectroscopy, and resonant inelastic soft X-ray scattering (RIXS) spectroscopy are powerful tools for obtaining information on the local orbital character of a specific element. These approaches are also used to probe occupied or unoccupied electronic states near the Fermi level (EF) and the structural symmetry of mixed-oxide systems. However, these spectroscopic techniques are sensitive to atomic symmetry because edge-sharing charge and charge distribution induce electron–electron and electron-orbital interactions, which may be related to the magnetic nature of the transition metal systems.
XANES spectroscopy is a sensitive tool that can be employed to probe unoccupied electronic states above EF and to analyze the structural symmetry of mixed-oxide systems [10, 12]. It can provide details on the electronic–orbital interaction from the transition metal 3d-O 2p hybridization states and the symmetry of the atomic structure. Therefore, the Ti L- and K-edges can be used to determine the valence states of Ti ions in LiTi2-xVxO4 (LTVO). The V ions occupying and doped in the Oh site may distort the crystal structure of LTVO because of the bonding of O–Ti–O as well as the unoccupied states in the 3d orbitals [34].
RIXS spectroscopic technique is used to explore the electronic structure of materials and to associate the structure with the XANES spectrum. RIXS is a process that describes the de-excitation of the final state of X-ray absorption, providing information on ground state via the excited intermediate states. Consequently, by tuning various excitation energies, certain RIXS features can be enhanced, allowing the separation of different electronic configurations in the mixed ground states [11, 30, 42]. The above conditions indicate that RIXS is a complementary tool compared with XANES. Unlike XANES, RIXS can be used to investigate a forbidden electronic transition (e.g., d-d or f-f excitation) because it involves two dipole-allowed transitions, given that its final state has symmetry similar to that of the initial state of the former. The RIXS of TM L-edge can reflect the 3d partial density of states and is regarded as a useful approach for analyzing the electron correlation among strongly correlated materials [31, 36, 45] as well as the charge transfer between TM 3d and O 2p orbitals.
In this research, XANES and RIXS spectra were applied to understand the influence of V doping on the atomic/electronic properties of the LTVO system and to discuss the basis of the quick suppression of superconductivity. The occupied or unoccupied states near EF of a solid-state solution may be a useful starting point in obtaining fundamental information on the complicated behavior of materials, including ferrites, high-Tc superconductors, and strongly correlated and ladder systems. These properties demonstrate that magnetic behavior and atypical physical and chemical characteristics can be synthesized and analyzed. The obtained X-ray spectra reveal that the rapidly suppressed superconductivity is associated with the variation of Ti-O hybridization mainly at eg bands rather than with the magnetic nature of the substituted V ion.
2. Experiments
All the LTVO samples were synthesized through conventional two-step solid-state reactions with highly pure oxides of TiO2 (99%), Li2CO3 (99.99%), and V2O3 (99%) [19]. The samples were dried at 150 °C for at least 2 h. Additional Li2CO3 (5 mol%) was added into the samples to compensate for lithium evaporation at high temperature. These processes were performed in a dynamic vacuum environment. In the first step, a mixture of Li2CO3 and TiO2 was pulverized and calcined at 750 °C for 8 h in ambient air. The mixture was pulverized and calcined again at 800 °C for 12 h to form the intermediate compound Li2Ti2O5. In the second step, the stoichiometric powders of Li2Ti2O5, Ti2O3, and V2O3 were mixed and ground and then cold-pressed into pellets. The pellets were wrapped with gold foil and sintered in an alumina crucible at 880 °C for 24 h in a dynamic vacuum environment at less than 10−5 torr. The final products were stored in an Ar-filled glove box or vacuum desiccator to prevent aging. Powder X-ray diffraction (XRD) patterns [19] with X-ray (Cu, Kα =1.5418 Ǻ) radiation in a diffractometer (Philips PW3040/60) confirmed the phase purity of the product and showed the variation of the lattice parameter as a function of V dopant. Different proportions of the dopant up to 2% were selected to understand the effect of dilute doping. Oxygen stoichiometry was expected to remain constant for all small concentrations given that the preparations were all the same.
XANES spectra were obtained from the National Synchrotron Radiation Research Center (Taiwan) and were operated at 1.5 GeV with a current of 360 mA. The K-edge of Ti and V K-edge of LTVO were measured with a wiggler beamline BL17C1 equipped with Si (111) crystal monochromators. The absorption spectra were recorded in the fluorescence-yield mode with a Lytle detector [27]. These hard X-ray absorption spectra, which could provide information on the unoccupied states with transition metal p state, were normalized to a unit step height in the absorption coefficient from below to above the edges. The oxide powders, namely, TiO2, VO2, Ti2O3, and V2O3, and standard metal foils were used for energy calibration and for comparing the electronic valence states. The XANES spectra at the Ti L- and O K-edges were determined at beamline BL20A in the total-electron-yield mode using an ultrahigh-vacuum chamber with pressure of ~5×10−9 torr. All spectra were normalized with the standard procedure.
The experiments for X-ray emission spectroscopy (XES) were conducted at beamline 7.0.1 at the Advanced Light Source, Lawrence Berkeley National Laboratory. The beamline is armed with a spherical grating monochromator and an undulator (period 5 cm in 99 poles) [3]. The RIXS spectra were recorded with a high-resolution grating spectrometer at grazing incidence with a 2D detector [17]. The resolution for Ti L emission spectra was about 0.4 eV. The monochromator resolution was set up similar to that of the emission measurements.
X-ray absorption at the Ti L-edge determined that the electron in the Ti 2p core level was excited to the unoccupied Ti 3d and 4s orbitals. XES recorded the signal from the decay process related to the partial densities of Ti 4s and 3d states. RIXS spectra were acquired by tuning different excitation energies according to the x-ray absorption spectral profile to measure XES. Sample current mode was employed to record XANES with an energy resolution of ~0.15 eV. Meanwhile, a high-resolution grazing-incidence grating spectrometer with a 2D multi-channel plate detector was used to record XES at a resolution of 0.6 eV [36].
3. Results and discussion
3.1. Structure of LTVO
The crystal structure of cubic spinel LTO, which belongs to the Fd3m space group, is illustrated in Fig. 1(a). The structure demonstrates that the lattice parameter of LTO is 8.404 Å (a = b = c) and contains eight AB2O4 units per unit cell. In general, a spinel structure has a total of 56 ions, 32 anions, and 24 cations per unit cell. The Li, Ti, and oxide ions are located at tetrahedral (Td) A-sites, octahedral (Oh) B-sites, and 32e sites, respectively. The XRD patterns of LiTi2-xVxO4 (x = 0, 0.05, 0.01, 0.015, and 0.02) are shown in Fig. 2(a). The result of the chemical analysis (determined with ICP-AES) is consistent with the nominal composition [19, 18, 24, 49]. These patterns reflect that the crystal structure is of pure spinel structure without an impure phase. The lattice parameter of LTVO samples displayed in Fig. 2(b) linearly decreases with the increasing concentration of the dopant. Doping V, which has a smaller ionic radius, induces a change in the lattice parameter when in a Ti site. This lattice shrinkage can be attributed to the fact that the ionic radius of V3+ (0.64 Å) is smaller than that of Ti3+ (0.67 Å) in the Oh site [29]. The rate of shrinkage of the lattice parameter is ~3.6 Å/at% based on the occupancy of Oh sites. This rate is also related to the bond length between the cations (Ti and V) and oxygen. Electronic structure strongly depends on the hybridization states of the transition metal 3d-O 2p orbitals nearby EF when electronic exchange normally occurs. Thus, the changed electronic structure around the transition metal ions greatly affects the oxidation state and physical properties of the latter. Considering these physical properties in AB2O4 with mixed-valence states require wide-ranging knowledge of their electronic structure, particularly the p-d hybridization and spin-orbital symmetry. Several experiments and theories show that AB2O4 exhibits strong electron–hole correlations because of the TM ions located in various sites [8, 39].
Figure 1.
Crystal structure of LTO [Li (green), Ti (blue), and O (grey)].
Figure 2.
(a) Powder XRD patterns of LTVO crystals with x = 0, 0.005, 0.01, 0.015, and 0.02. The patterns are fitted to the Fd3m space group and are indexed. (b) Chemical composition of V dependence of the lattice constant of LTVO.
3.2. Resistive properties
The transport properties of the samples are specified in Fig. 3(a) with V doping of less than 0.025. The findings indicate that the superconducting Tc is suppressed with an increasing proportion of the dopant. Fig. 3(c) reveals that the resistivity of the samples gradually increases. The un-doped LTO has a superconducting Tc of ~12 K with a transition width (△Tc) of ~0.4 K. Fig. 3(b) indicates that when the Ti ion is replaced with V ions, Tc exhibits an abrupt but linear suppression with respect to the level of doping. Given the magnetic pair-breaking effects [47], the doped magnetic ions suppress superconductivity. Considerable research has been devoted to exploring cuprate [48]; Tarascon et al., 1987) and pnictide [41] superconducting systems based on resistivity measurements. For the LTO series, the effect of doping with both nonmagnetic and magnetic impurities at both Td and Oh sites on (Li1-xAx)(Ti2-yBy)O4 [A = Mg and Mn; B = Al and Cr] compounds has been previously reported [26]. The substitution of nonmagnetic ions (e.g., Mg2+ at the Td site and Al3+ at the Oh site) slightly suppresses superconductivity similar to the case when Li+ ions occupy the Td site. However, the effect of superconductivity suppression is greater when the magnetic Mn2+ ions occupy the Td site. The suppression of superconductivity is attributed to pair-breaking when the Cooper pairs are scattered with magnetic impurities. The effect of substituting Ti3+ with Cr3+ at the Oh site is even more significant.
Figure 3.
(a) Transport properties of LTO and LTVO samples at low temperature without magnetic field. (b) Chemical composition of V-dependence of superconducting Tc. (c) Resistivity at room temperature.
The resistivity near 300 K increases as x increases [Fig. 3(c)], indicating the extreme sensitivity of the transport properties to the electronic effect of 3d transition metals. The itinerant carrier density can be attributed to the cation (Ti3+) in LTO. Similar to the reports of a previous study on Al-doped LTO [16], the results of the current study clarify the effect of carrier density on superconductivity, such that the resistivity increases with the level of doping in the normal state. Except for the semiconducting behavior at the normal state, a similar Tc has been determined in LiTi1.7, Al0.3O4, and LTO samples [19]. This observation implies that Tc is slightly affected by substituting a considerable proportion of the trivalent non-magnetic ions. The ratio Ti4+/Ti3+ in Oh symmetry can then be modulated with impurity doping to vary the superconducting properties of LTO. Electron–electron interaction may be a key factor in causing changes in the transport properties of the samples. By distorting the local symmetry of the spinel structure, V substitution will not only alter the valence of Ti, but the hole/electron effect as well. This phenomenon is discussed in the next section.
3.3. Electronic structure results based on x-ray spectra
With the aim to investigate the effects of V dilute doping on LTO, this research measures XANES and RIXS at Ti L-edges. As shown in the inset in Fig. 4(a), the Ti L-edge XANES spectra exhibit several well-resolved features because of the excitations of a 2p core electron into the Ti 3d empty states, that is, a transition from the ground state with configuration 2p63dn to an excited electronic configuration 2p53dn+1 with numerous multiplet excitations. When the spin-orbital coupling is in the transition metal 2p state, the spectra reveal two prominent features located at the energy ranges of 455 eV to 461 eV and 461.2 eV to 468 eV, corresponding to the absorptions L3 (2p3/2 → 3d) and L2 (2p1/2 → 3d) edge respectively. These prominent features are due to a strong Coulombic interaction between the poorly screened Ti 3d electrons and the Ti 2p core hole [12]. L2 edge features are normally broadened compared with the L3 edge because of the lesser lifetime of the 2p1/2 core hole (i.e., a radiationless electron transition from energy level 2p3/2 to the 2p1/2), accompanied by the promotion of a valence electron into the unoccupied states (conduction band). In the Oh crystal field, the 3d band splits into t2g (dxy, dxz, and dyz) and eg (dx2-y2 and 3d3z2-r2) subbands [∆ = (eg) − (t2g) = 10 Dq]. Given the Oh crystal-field splitting, the Ti L3-edge feature possesses t2g and eg bands. The RIXS Ti 3d spectra of LTO and doped LTO (V 2 %) are exhibited with energy-loss scales in Fig. 4(a). Four distinct spectral features are observed in RIXS spectra. These features are as follows: elastic peak at the energy loss at zero, d–d excitations at about 4 eV, a broad-band feature at around 7 eV, and a large energy dispersed-feature above 10 eV. Letters a to k denote the different exciting energies based on the XANES spectra, as displayed in the inset of Fig. 4(a). For example, XES spectrum b is collected by tuning the incident photon energy at 457 eV in XANES. The inelastic scattering features ranging from 5 eV to 10 eV originate from the complicated charge-transfer excitation from O 2p to Ti 3d\n\t\t\t\t\tt2g and eg subbands [1, 31]. The low-energy inelastic scattering features absent in TiO2 are observed at energy of less than 5 eV [36]. The spectra within this energy range significantly differ from that of TiO2. The appearance of Ti3+ implies that an electron occupies the empty 3d\n\t\t\t\t\tt2g orbitals, thus inducing the energy-loss features. Strong d-electron correlation is revealed because the relative intensities of peaks A4 and B4 (d-d excitations) are observed to be markedly different at varying excitation energies. An enhanced energy-loss peak is observed at 1 eV in spectrum a, and the intensity of this peak intensively drops when the excitation energy is tuned to a higher energy (peak b in XANES). With the increase of excitation energy at c, another intense peak at energy loss of about 2.9 eV is observed. An excitation energy tuned below the L3\n\t\t\t\t\tt2g peak in the spectrum (letter a) enhances inelastic scattering A4, which is uncommon. This enhanced inelasticity is not observed at either t2g (b) or eg (d) resonant energy. This phenomenon can be explained by considering the presence of Ti3+, as revealed by the constant-initial-state absorption spectrum [3]. The spectral shapes in XANES spectra are similar for both LTO and LTVO, wherein spectral differences are slightly small. Given that the spectral change of XANES is small with V doping, the spectral deconvolution and specific electronic state can be measured separately from RIXS [11]. The result at a specific energy (c) in Figs. 4(b) and 4(c) indicates that an enhanced trivalent Ti contribution is observed at a dip quadrivalence within the spectrum (between t2g and eg). The Ti3+\n\t\t\t\t\tt2g- and eg-resonance energies correspond to the excitation energies 456 and 457.5 eV respectively. [3].
Figure 4.
(a) Ti L-RIXS spectra of LTVO (x = 0 and 0.02) recorded with several excitation energies labeled with letters a to k in the Ti XANES L-edge spectrum. Ti L3 RIXS spectra at (b) Ti3+ t2g-resonance and at (c) Ti3+ eg-resonance. The insets of (b) and (c) display the energy diagram of the d-d excitation.
When excitation energy is tuned to the t2g resonance, the low-energy-excited feature C4 at ~1 eV demonstrated in Figs. 4(b) and 4(c) is resonantly enhanced. This feature corresponds to the electron-hole pairs within the t2g band. When the spectrum is acquired with energy at about eg resonance energy [Fig. 4(c)], the intensity of peak D4 increases. Such an increase can be attributed to the transition between the occupied t2g and the unoccupied eg states. The presence of this RIXS feature indicates a strong electron–electron association. The d-d excitation peak at an energy loss of about 2.9 eV corresponds to the crystal-field splitting (i.e., 10 Dq) and refers to the ground state without the core hole. The comparison of the spectra of each set shows that the intensity of the loss feature decreases with the increasing concentration of dopant (x = 0.02). Hence, fewer electrons are distributed in the t2g band. In a previous study on TiO2 [31], no obvious feature was exhibited in the region located below the elastic signal (peak). The change in intensity is due to the variation of the incompletely filled t2g band arising from the V doped effect. This result forcefully indicates that the Ti valence is enhanced when V is doped. The active Ti ions in LTO have a formal oxidation state trivalence and quadrivalence, which display nearly 0.5 electrons in the 3d orbital, and possess a lesser electronic density. Doping with V reduces the number of Ti 3d electrons, suggesting an increase in the formal oxidation number of the Ti ion. The Ti ions show a mixed-valence state and contain some t2g electrons in LTO. With no t2g electron, d-d excitation is absent because no electron subsists in t2g to be excited to the t2g/eg unoccupied state. A little variation in valence of Ti is then reflected in the RIXS spectra. The diminution or absence of features in the energy range from 0 eV to 5 eV indicates a decrease in d–d transitions. More electrons occupy the t2g orbital when the oxidation number of Ti changes from trivalence to quadrivalence. The probability of exciting the t2g electron into the unoccupied states (t2g or eg) is therefore increased. Only RIXS can observe the d-d excitations (t2g-t2g and t2g-eg) in the spectra. The significance of observing this d-d excitation is that the t2g occupation number changes with V doping, whereas the number of t2g electrons decreases with V doping. Therefore, the significant RIXS spectrum can observe this kind of valence change.
Figure 5.
(a) XANES Ti L3,2-edge spectra for LTVO (x = 0.005 to 0.02), LTO (x = 0), Ti2O3, and anatase TiO2. (b) Integrated area ratio of A5/B5. This ratio increase implies the presence of 3d0 states. (c) Total area of L3-edge (A5+B5) decreases with the increase of V concentration
Complementary information is also acquired for this research by thoroughly analyzing the XANES Ti L3,2-edge spectra. The spectra of LiTi2-xVxO4 (or LTVO) (x = 0 to 0.02) are presented in Fig. 5(a). The white line shapes of the spectra of LTO (undoped) and slight V doping (x = 0.005) in LTO are similar. The A5 and C5 features (B5 and D5) are previously assigned as the t2g (eg) states of the 10 Dq crystal-field-split in 3d orbitals. This Oh crystal-field splitting is ~1.8 eV at LTO, but increases from 1.8 eV to 2.0 eV when the V concentration increases from x = 0.005 to x = 0.02. This phenomenon reveals the distortion of Oh symmetry when Ti is replaced with slight V doping. This finding is consistent with the powder XRD results and the theoretical calculations [12, 13, 15]. Moreover, the results specify that B5 peak broadens with its gradual V doping. As previously reported [12, 13, 15], and according to the Jahn-Teller distortion with ∆EJ-T energy splitting in the eg band, the eg orbitals point directly toward the Ti 2p orbitals of the octahedrally coordinated O atoms. In general, eg band is sensitive to the local environment, producing a changed bonding distance and a O–Ti–O angle in the presence of V doping. These eg-related peaks are also broader than the t2g peak because of the larger hybridization between eg orbitals and O ligand states, and because of the associated effects of solid-state broadening [12]. The eg feature appears as a narrow and symmetric profile in LTO, representing symmetric octahedrally coordinated Ti–O bonds. This feature becomes broad and asymmetric upon doping, suggesting a distortion. In particular, distortion may arise from the uneven Ti-O bonds in the Oh symmetry. The eg peak at the side with greater energy originates from the short Ti-O bonds because of the increase in hybridization (relative to the long Ti-O bonds); hence, the intensity ratio of the high-energy to low-energy eg peaks is increased with V doping. This result implies that long Ti–O bonds become shorter [17]. An enhancement in the integrated area under A5 peak implies the increase in unoccupied states of Ti 3d states, thereby indicating that the Ti valence increases with slight V doping. From the Ti–O bond, the electronic configuration of Ti exhibits a combination of 3d0 (t2g0eg0) and 3d1 (t2g1e0) in the ground state. Fig. 5(b) shows the integrated area of ratio A5/B5, which clearly increases with V doping. Consequently, the more intense A5 (t2g) feature implies a higher oxidation number and exhibits the presence of Ti4+ (3d0) [28, 40]. Moreover, the area of the L3-edge that corresponds to (A5+B5) progressively decreases when V concentration increases [Fig. 5(c)] because V replaces Ti. This trend is in good agreement with the XRD results [18]. A small but actual increase in Ti valence with slight V doping is observed in XANES Ti L3,2-edge spectra. Such an increase is significantly obvious in the Ti L-RIXS spectra.
The pre-edge features of Ti K-edge XANES spectra are displayed in Fig. 6(a). These spectral features at K-edge are due to the transitions from the Ti 1s core level to the 4p-derived final states based on the dipole selection rule. The pre-edge features are a combination of strongly hybridized Ti 4sp and 3d and O 2p orbitals. Quadrupole-allowed transitions generally occur at the pre-edge region in the transition metal oxides, which correspond to the contribution from 3d orbitals through 4sp-3d hybridization [14, 25, 37]. The inset of Fig. 6(a) reveals that a Gaussian function is subtracted from the original Ti K-edge spectrum for a detailed comparison of the pre-edge spectra. Fig. 4(a) shows the Ti K-edge spectra of LTO and LTVO (0.005 to 0.02). As marked by the black arrow in Fig. 6(a), the spectra of LTVO with a small concentration of x from 0.005 to 0.01 are similar to that of LTO with the same photon energy at the main peak A6. The Ti valence performs to maintain +3.5 owing to the smaller concentration of V doping. Nevertheless, the intensity of the pre-peak spectrum increases relative to that of pure LTO as the doping level is increased to x = 0.015 and x\n\t\t\t\t\t= 0.02. Meanwhile, as directed by the red arrow in Fig. 6(a), chemical shift is also observed as V concentration increases. Fig. 6(b) displays the pre-edge region between 4969 and 4977 eV, as well as the three main features (i.e., C6, D6, and E6) in XANES Ti K-edge spectra of TiO2 (anatase, Ti4+) and LTVO (x = 0, 0.02) samples. The origin of the splitting of pre-peaks is caused by local excitations (1s to 3d\n\t\t\t\t\tt2g and eg) [5, 14, 38, 46]. Conversely, the greatest contribution to this splitting is suggested to be the corner- and edge-sharing Ti octahedra that yield non-local, intersite hybrid excitations. The next-nearest neighbor 3d states (t2g and eg) are related Ti 4p states that absorb atom via the anion O 2p states [7, 23, 44]. The local structure of Ti for LTO and LTVO also possesses Oh symmetry; hence, the pre-peak region (A6 and B6) can be described in terms of a similar scenario [23, 44, 7]. The intensity of these pre-peaks varies with V concentration. In the V-doped LTO, the substitution of V for Ti slightly decreases the lattice parameter [18]. A reduced bond length (Ti–O–Ti) subsequently increases the overlap of the first-nearest-neighbors and the absorbing atom (e.g., Ti 4p-Ti 3d orbitals) mediated by O ion. Therefore, these pre-peaks are closely related to the increase in the number of the first-nearest-neighbor unoccupying the Ti 3d states. These intersite hybrid peaks intensities increase with the increase of V concentration. The inset of Fig. 6(b) shows that the variation in the area under the pre-peak suggests that the 3d unoccupied states are altered via the interaction of the Ti 4p-O 2p-Ti 3d states. These results strengthen the conclusion that Ti is in mixed-valence states between LTO and LTVO [14, 24]. The analysis of the spectra of LTO and LTVO (x = 0.02) reveals that pre-peaks A6 and B6 are stronger in LTVO than in LTO, attended by a chemical shift of the main peak to higher energy. Therefore, Ti valence is increased when V is doped. The average valence of Ti in the case of doped LTVO (x = 0.015 and 0.02) is approximately +3.6, which is obtained with a simple calculation and a fit of the ratio of areas under the spectral lines.
The O K-edge XANES spectra [Fig. 6(c)] provide useful information about the unoccupied density of states in TMO because of the covalent mixing between O and TM ions. The two pre-edge features are at about 530 eV to 536 eV because of the strong hybridizations in Ti 3d–O 2p states, and correspond to the t2g and eg states of Ti 3d orbitals respectively. The intensity of the t2g and eg peaks at the O K-edge changes is similar to an increased peak ratio t2g/eg in Ti L-edge XANES. In sum, the above results specified by the XANES and RIXS spectra strongly confirm that the valence of Ti is increased when the doping level of x increases. Thus, the Ti-O hybridization and electron–electron correlation are modified when a slight doping of V ions completely suppresses the superconductivity of LTO.
Previous studies have indicated that LTO is a spinel superconductor, whereas spinel LVO reveals a heavy fermionic behavior with a Curie-Weiss spin susceptibility and a large electronic specific heat. Conduction arises on a Ti sublattice via the t2g orbitals with a narrow bandwidth (2 eV to 3 eV), displaying possible strong electronic correlations. The origin of the physics and electronic properties of the spinel structure are yet to be resolved. Our current research demonstrates the role of 3d electrons in the properties of LTO and LTVO. The full solid solution of LiTi2−xVxO4 (0 ≤ x ≤ 2) has been investigated [24]. The replacement of V ions for Ti site modifies the bandgap and d electron/hole exchange in Ti energy levels in order to maintain electrical neutrality. Several mechanisms for understanding the quickly suppressed superconductivity with a slight doping of LTVO have been proposed. The slight doping of LTVO may incur two major electronic effects. The first one is a simple pair-breaking effect with electron spin S = 1 on superconductivity [20, 24]. The second one refers to the effect of carrier doping on electron correlation via band filling. The 3d electrons of V are assumed to hybridize the Ti conduction electrons, making them itinerant. A simple magnetic pair-breaking of electron spins induced by additional impurity is commonly assumed to be responsible for suppressing superconductivity based on the localized moments of 3d electrons of V [24]. The localized magnetic moment per V atom is estimated to be 1.7 μB in the V4+ state with S = 1/2 [24]. The XANES measurements at V K-edges plotted in Fig. 7 show that V is more likely to be in state 3+ (Bordage et al., 2110), which contains a d2 electronic configuration and is supposed to offer a weak magnetic moment probably because of the antiparallel orientation of the electron spins. The decreased V magnetic moment is also obvious in LiZnV2O4 [35]. A second possible reason for a weak magnetic moment is the decreased charge carriers at Ti t2g bands. In this case, V electrons are expected to be localized at the Ti conduction electrons. If the Ti ions in LTO possess oxidation numbers 3+ and 4+, then ~0.5 (t2g) electrons are expected to be in the conduction band. This condition results in the observation of a d-d excitation within the energy range of 0 eV to 5 eV owing to the presence of electrons in the t2g occupied state that are excited to either the t2g or eg unoccupied state. The number of electrons occupying the t2g orbital is expected to decrease if the oxidation number of Ti increases from trivalence to quadrivalence because of the doping of V ions. The spectra in RIXS reveal a significant variation in the d-d excitation feature, which suggestively decreases when LTO becomes LTVO, even with slight doping of V ions. This situation shows the decreased Ti 3d occupied states with the increase of x concentration. The Ti t2g occupation number is then altered upon V doping. This valence variation is small in XANES Ti K- or L-edges spectra, but weighty in RIXS spectra. The results, particularly the reflection of the decreased intensities of t2g-t2g, and t2g-eg transitions from the RIXS spectra, support the role of these electronic states in rapidly suppressing Tc in slight V doping. Accordingly, the findings of this research support the conclusion that the decreased density of the states of Ti 3d electrons at EF is responsible for rapidly suppressing superconductivity.
Figure 6.
(a) XANES Ti K-edge spectra of LTVO (x = 0 to 0.2) and Anatase-TiO2 in the pre-edge region. The inset shows that a Gaussian function was subtracted from the original TiO2 spectrum. (b) Detailed comparison of the pre-edge region for LTO and LTVO (x = 0.02). (c) XANES O K-edge spectra shown with two main peaks in the pre-edge region corresponding to the hybridization of Ti 3d (t2g and eg)-O 2p states.
Figure 7.
XANES V K-edge of LTVO (x = 0.02) compared with the larger doping of LTVO (x = 0.05 and 0.1). No significant variation is observed in the spectra
4. Conclusion
The results on the effect of V doping on the atomic and electronic structures of LTVO, XAS, and RIXS spectra reveal that the valence of V ions remains constant, but the hybridization of Ti-O considerably varies. In particular, the results show the mixed valency nature of Ti ions and a significant variation in the hybridization of Ti 3d-O 2p states. The sharp decrease in the superconductivity of V-doped samples is ascribed to the electron–orbital interaction arising from the hybridization of TM and O orbitals. Low-energy excitation because of d-d excitation indicates that electron correlation and Ti oxidation number are enhanced, which support the XAS observation. Meanwhile, the observed properties of superconductivity are attributed to an altered density of the states of Ti 3d electrons and Ti-O hybridization. The Ti electronic configuration and lattice distortion induce the rapidly suppressed superconductivity and are attributed to hybridization rather than to the magnetic nature of the substituted ion. This research also demonstrates that RIXS is a powerful tool for investigating the electronic states and electron correlations of Ti compounds, in which the XANES spectral features are subdued.
\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/47862.pdf",chapterXML:"https://mts.intechopen.com/source/xml/47862.xml",downloadPdfUrl:"/chapter/pdf-download/47862",previewPdfUrl:"/chapter/pdf-preview/47862",totalDownloads:1942,totalViews:302,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:0,impactScore:0,impactScorePercentile:11,impactScoreQuartile:1,hasAltmetrics:0,dateSubmitted:"June 16th 2014",dateReviewed:"October 16th 2014",datePrePublished:null,datePublished:"August 24th 2015",dateFinished:"November 18th 2014",readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/47862",risUrl:"/chapter/ris/47862",book:{id:"4535",slug:"superconductors-new-developments"},signatures:"Chi-Liang Chen and Chung-Li Dong",authors:[{id:"146575",title:"Dr.",name:"Chi-Liang",middleName:null,surname:"Chen",fullName:"Chi-Liang Chen",slug:"chi-liang-chen",email:"clchen@phys.sinica.edu.tw",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"146584",title:"Dr.",name:"Chung-Li",middleName:null,surname:"Dong",fullName:"Chung-Li Dong",slug:"chung-li-dong",email:"dong.cl@nsrrc.org.tw",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. Experiments",level:"1"},{id:"sec_3",title:"3. Results and discussion",level:"1"},{id:"sec_3_2",title:"3.1. Structure of LTVO",level:"2"},{id:"sec_4_2",title:"3.2. Resistive properties",level:"2"},{id:"sec_5_2",title:"3.3. Electronic structure results based on x-ray spectra",level:"2"},{id:"sec_7",title:"4. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'AguiAUozumiTMizumakiMKäämbraT2009Intermetallic charge transfer in FeTiO3 probed by resonant inelastic soft x-ray scattering. Physical Review B, 79: 092402.Agui, A.; Uozumi, T.; Mizumaki, M. & Käämbra, T. (2009). Intermetallic charge transfer in FeTiO3 probed by resonant inelastic soft x-ray scattering. Physical Review B, 79: 092402.'},{id:"B2",body:'AnisimovV. IKorotinM. AZölflMPruschkeTHurKLe & Rice, T. M. (1999Electronic Structure of the Heavy Fermion Metal LiV2O4. Physical Review Letters, 83: 364.Anisimov, V. I.; Korotin, M. A.; Zölfl, M.; Pruschke, T.; Hur, K. Le & Rice, T. 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Physical Review B, 42: 8752(R)'},{id:"B48",body:'XiaoGStreitzF. HGavrinADuY. WChienC. L1987Effect of transition-metal elements on the superconductivity of Y-Ba-Cu-O. Physical Review B, 35: 8782(R)Xiao, G.; Streitz, F. H.; Gavrin, A.; Du, Y. W. & Chien C. L.(1987). Effect of transition-metal elements on the superconductivity of Y-Ba-Cu-O. Physical Review B, 35: 8782(R)'},{id:"B49",body:'XuFLiaoY. CWangM. JWuC. TChiuK. FWuM. K2003The Preparation Effect of Li1+x Ti2O4 and Its Aging Effect. Journal of Low Temperature Physics, 131569574Xu, F.; Liao, Y. C.; Wang, M. J.; Wu, C. T.; Chiu, K. F. & Wu, M. K. (2003). The Preparation Effect of Li1+x Ti2O4 and Its Aging Effect. Journal of Low Temperature Physics, 131: 569-574.'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Chi-Liang Chen",address:null,affiliation:'
Institute of Physics, Academia Sinica, Nankang, Taipei, Taiwan
National Synchrotron Radiation Research Center (NSRRC), Hsinchu, Taiwan
Institute of Physics, Academia Sinica, Nankang, Taipei, Taiwan
National Synchrotron Radiation Research Center (NSRRC), Hsinchu, Taiwan
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1. Introduction
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Myelodysplastic syndromes (MDS) are characterized by peripheral blood cytopenias secondary to the ineffective hematopoiesis, and represent a heterogeneous group of clonal hematologic malignancies in which abnormal multipotent progenitor cells are involved. As a result, there is an increased risk of bleeding diathesis and anemia requiring frequent transfusions, infections, and progression to acute myeloid leukemia [1, 2, 3, 4]. It is a very well-known fact that a large spectrum of genetic mutations is involved in MDS pathogenesis that may affect clinical outcome and response to the treatment. These genetic mutations may control cell cycle by affecting key proteins of spliceosome, DNA repair, kinase signaling, tumor suppressor genes, and transcription factors, changing bone marrow micro environment, resulting in hypercellular bone marrow with peripheral cytopenias through enhanced programmed cell death (PCD) and bone marrow dysfunction [5, 6]. To overcome programmed cell death, hematopoietic growth factors such as erythropoiesis stimulating agents (ESAs) and granulocyte colony stimulating factor (G-CSF) are the 1st step in management of the low-grade MDS recommended by the American Society of Clinical Oncology (ASCO) to reduce early apoptosis [1].
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Thrombopoietic stimulating agents (TSAs), ESAs, G-CSF, antithymocyte globulin (ATG) [7], lenalidomide [8], and hypomethylating agents are some of the non-transplantation options for management of the MDS patients suggesting that immune dysregulation plays a pivotal role in MDS pathogenesis [1]. Although its etiology is not clear, it has been shown that natural killer (NK) cell activity and its response to chemokines is decreased in MDS, and natural killer cells will be progressively more dysfunctional with MDS progression [9]. It has been shown that although dysfunctional regulatory T-cells (Treg), cells in charge of suppressing T helper (Th) activity, contribute in early stages of MDS, Th expands in the later stages of MDS, and there function is significantly reduced with treatment [10].
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Tumor necrosis factor alpha (TNF-α) level is higher in bone marrow and peripheral blood plasma of MDS patients, and may reflect an unfavorable outcome [11, 12]. Study shows that plasma level of 19 cytokines are significantly altered compared with normal individuals, among all of them, C-X-C motif chemokine 10 (CXCL10) and interleukin 6 were associated with shortened survival [13]. The relationship between shorter survival and interleukin 6 levels is very well known, and high producing genotypes of both TNF-α and interleukin 6 are highly associated with transfusion dependency for both anemia and thrombocytopenia, and severity of the bicytopenias [14]. Interferon regulatory factor-1 (IRF-1), a transcriptional activator of interferon system, has anti oncogenic properties, inhibits tumor formation, and regulates innate immune response. It has been shown that IRF-1 mRNA is 10 fold decreased in MDS patients, while it is increased in MDS patients with autoimmune disorders, showing that IRF-1 may promote inflammation and autoimmunity and has a protective roll in MDS patient’s [15].
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Although it has been reported that MDS is significantly associated with autoimmune disorders, it may occur secondary to the autoimmune disorders per se [16] or exposure to the therapeutic agents used for treatment of autoimmune disorders. A retrospective study in Sweden on 1662 MDS patients and 42,878 matched controls revealed that underlying autoimmune disorder increased risk of MDS by 2.1 with highest risks observed with prior autoimmune hemolytic anemia (AIHA), polyarteritis nodosa (PAN), granulomatosis with polyangiitis (GPA), giant cell arteritis (GCA) and aplastic anemia. It was speculated that chronic stimulation of the immune system may act as a trigger and prone the patient to MDS [17]. In a retrospective study of 2471 patients, it was found that MDS occurred subsequent to autoimmune disorders, most commonly rheumatoid arthritis, Sjogren’s syndrome, systemic lupus erythematosus, polyarteritis nodosa, discoid lupus erythematosus, and pernicious anemia were associated with MDS [18]. In a case control study of 80 for MDS patients, it was found that there is strong and statistically significant evidence that MDS occurred after autoimmune disorders with Grave’s disease and Hashimoto’s thyroiditis were among the most important disorders [19]. There is a case report of limited granulomatosis with polyangiitis (GPA) treated with corticosteroids, who did develop myelodysplastic syndrome, papillary thyroid carcinoma, and gastric adenocarcinoma [20].
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There are several reports regarding therapy related MDS in population with autoimmune disorders who underwent disease modifying antirheumatic drugs (DMARDs) therapy. In a retrospective case-control study of 40,011 patients with 27 kinds of autoimmune disorders, 311 patients met the inclusion criteria, 86 of them had MDS, and found azathioprine exposure has increased 7 fold myeloid neoplasms in a median of 8 years. In this study, methotrexate, and mycophenolate mofetil did not elevate the risk of myeloid neoplasms [21]. However, there is a case report regarding association of low-dose oral methotrexate therapy with MDS in a rheumatoid arthritis patient [22]. In another study, from 370 rheumatologic patients who received azathioprine for at least 1 year, 59 patients underwent bone marrow examination and 2 of them found to have MDS. This study revealed that risk of secondary MDS is 100 fold higher in patients who received azathioprine for their rheumatologic disorders. Chromosomal examination of the patients with MDS secondary to the azathioprine showed abnormalities of chromosome 7 in majority of them (8 out of 10) [23]. There is also evidence that MDS patients who have autoimmune disorders might respond to hypomethylating agents such as azacitidine and decitabine [24].
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2. Rheumatologic manifestations of MDS
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It is a very well-known fact that about 10–30% of MDS patients may present with a variety of autoimmune or laboratory manifestations or develop an autoimmune disorder. These manifestations are polymorphic and include leukocytoclastic vasculitis, clubbing, peripheral neuropathy, autoimmune hemolytic anemia, polyarthritis, myositis, acute or systemic vasculitis, Raynaud’s phenomenon, polyarteritis nodosa, vitiligo, iritis, colonic ulcerations, pulmonary involvement, and reported autoimmune disorders include rheumatoid arthritis, Sjogren’s disease, giant cell arteritis, polymyalgia rheumatica, relapsing polychondritis, Behçet’s disease, and systemic lupus erythematosus. Although autoimmune manifestations are mostly seen during the course of MDS, autoimmune disorders may occur before MDS diagnosis. Laboratory manifestations of MDS include hypergammaglobulinemia, hypogammaglobulinemia, monoclonal gammopathy, positive direct antiglobulin test (DAT), positive ANA, rheumatoid factor, cryoglobulinemia, and anti-double-stranded DNA.
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3. Autoimmune disorders in myelodysplastic syndrome
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Several studies support that autoimmune disorders may occur in the setting of MDS, and treating MDS with immunosuppressors may improve the autoimmune disorder. Although there were several case reports of MDS preceding autoimmune disorders, the first comprehensive retrospective study in 1986 on 104 MDS patients revealed two patients had pernicious anemia, two had hypothyroidism, and one had both pernicious anemia and hypothyroidism [23]. Later, in a retrospective study in 1994, five patients with MDS reviewed and revealed polyarthritis with positive rheumatoid factor (RF) and necrotizing vasculitis [25]. In another retrospective study in 1995, 221 patients with MDS reviewed and found 30 patients with autoimmune disorders, and categorized patient to three categories of acute systemic vasculitis or autoimmune disorder, chronic or isolated autoimmune phenomena, and classic connective tissue disorders. Skin vasculitis, arthritis, and fever were among the most common autoimmune manifestations [26].
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A case series in 2002 showed various autoimmune paraneoplastic disorders including vasculitis, pyoderma gangrenosum, Coombs negative autoimmune hemolytic anemia, autoimmune thrombocytopenia, and chronic inflammatory demyelinating polyneuropathy (CIDP) with good response to immunosuppressive therapy [27]. In a retrospective review of 235 MDS patients autoimmune manifestations such as skin vasculitis (24%), noninfectious fever (13%), arthralgia and arthritis (13%), peripheral neuropathy (10%), and pulmonary infiltrates (8%) were more common than systemic vasculitis [28]. In a cohort of 1408 patients with MDS, 391 (28%) had autoimmune disorders, with hypothyroidism (44%), as the most prevalent, and idiopathic thrombocytopenic purpura (12%), rheumatoid arthritis (10%), and psoriasis (7%) were among the common manifestations of autoimmune diseases [29].
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In a retrospective study of 67 MDS patients with autoimmune diseases, neutrophilic dermatosis was the most common autoimmune disease (35.8%), followed by Behçet’s disease (14.9%), and rheumatoid arthritis (13.4%) [30].
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3.1. Vasculitis
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The association between MDS and vasculitis is rare, but more common than solid tumors, and has been described for decades. Cutaneous vasculitis presents by palpable purpura mainly in lower extremities that involves small vessels and is characterized by perivascular inflammation and vessel wall damage by infiltrating neutrophils. Although both cutaneous and systemic vasculitis has been reported in MDS patients, at times they can be seen together in MDS patients. For instance, in a case series of 6 biopsy proven cutaneous vasculitis patients with MDS, 3 patients had evidence of systemic vasculitis [31]. In one case, MDS patient with biopsy proven cutaneous vasculitis developed acute myeloid leukemia within 4 months of vasculitis diagnosis [32]. Henoch-Schonlein purpura, a small vessel vasculitis with IgA dominant immune deposits has been described in MDS patients [33].
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The association of MDS and polyarteritis nodosa (PAN) type medium-vessel vasculitis has been reported [34]. In a retrospective study of 8 patients with chronic myelomonocytic leukemia (CMML), with vasculitis involved the medium-vessel, fulfilling the criteria for classic PAN, the presentation was non-specific, and patients developed atypical manifestations [35]. There is a case report of 43-year-old man who qualified for a diagnosis of PAN and developed systemic vasculitis at the time of chronic myelomonocytic leukemia (CMML) diagnosis [36]. There is a report of two cases with CMML who presented with PAN-like systemic vasculitis with bilateral perirenal hemorrhage and negative antineutrophil cytoplasmic antibody with improvement of vasculitis with systemic steroids [37].
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Although most MDS associated vasculitis described as leukocytoclastic vasculitis, published case reports documented large vessel vasculitis as autoimmune complication of MDS. Aortitis has been reported as an autoimmune manifestation of an MDS patient at presentation [38]. There is a report of two MDS cases that presented with acute large vessel vasculitis with rapid improvement with systemic steroids [39]. In a retrospective analysis of 271 temporal arteritis patients, it was found that 20 patients had malignancy, of which 11 patients had MDS, favoring a relationship between large vessel vasculitis and MDS [40]. There is a case report of Takayasu’s arteritis diagnosed shortly after diagnosis of MDS, with progression to AML regardless of improvement of vasculitis with immunosuppressive treatment [41]. There is a case report of a 71-year-old woman presenting with fever, neck pain, anemia, and thrombocytopenia, with positive positron emission tomography (PET)/CT scan of the aorta and carotid arteries with negative temporal artery biopsy who received the diagnosis of MDS after a bone marrow aspiration analysis [42, 43].
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3.2. Behçet’s disease
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A multisystem, chronic inflammatory disease of unknown etiology, Behçet’s disease (BD) is characterized by recurrent oral and genital ulcers, uveitis, arthritis, and vascular involvement of several organs including pulmonary, central nervous system and gastrointestinal tract. In a retrospective study of 805 BD patients, 16 patients had MDS, from which 43.8% had BD prior to MDS, 18.7% diagnosed after MDS and 37.5% had concurrent BD and MDS. It has been shown that trisomy 8 has been accumulated in all of BD patients with MDS, and these patients more likely to be female, older age, and have fever and ileocecal ulcerations [44]. In a retrospective study of 46 MDS patients, 8 patients had trisomy 8, 5 of them had multiple intestinal ulcers, a common feature of BD. Two of the MDS patients with trisomy 8 and multiple intestinal ulcers were treated with granulocyte-colony stimulating factor (G-CSF), aggravating their symptoms, suggesting G-CSF should be used cautiously in this subgroup of MDS patients [45]. There is several case reports of BD associated with MDS [46, 47, 48, 49]. In a case report of two patients with BD and MDS, it has been suggested that PET/CT may help diagnosis of both BD and MDS with high uptake by bone marrow in MDS patients and genital and gastrointestinal aphthous ulcers in BD patients [50]. It has been suggested that the frequency of gastrointestinal involvement is more common in MDS-associated BD patients than general BD population [51].
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3.3. Inflammatory arthritis
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There are several case reports and small series of inflammatory arthritis and MDS co-occurrence. In a retrospective study of 28 MDS patients, 8 had acute seronegative inflammatory arthritis with good response of arthritis to steroids [52]. In a French multicenter retrospective study of 22 patients with MDS, 77% of patients had polyarthritis, and 68% had symmetric joint involvement. Radiologic erosions are rare, and MDS associated arthritis is more frequent in refractory anemia with excess blast (RAEB) [53].
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3.4. Miscellaneous
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There are several case reports of relapsing polychondritis (RP) presenting as a paraneoplastic disorder in the setting of MDS [54, 55]. In a retrospective study of hematological changes in 19 patients with relapsing polychondritis, MDS was found in three RP patients [56]. Autoimmune hemolytic anemia has been reported in association with MDS [57, 58, 59]. Association of systemic lupus erythematosus and MDS has been reported [60, 61, 62].
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3.5. Immunological abnormalities
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It is a very well-known fact that a spectrum of immunological abnormalities occur in MDS. In a retrospective study of 104 MDS patients, 12.5% had monoclonal gammopathy, 19% had low immunoglobulin levels, 32% had polyclonal rise in serum immunoglobulin level, and 8.1% had positive direct antiglobulin test (DAT) [25]. In a case series of 142 patients with MDS and CMML, 23.2% had non-organ specific autoantibody ANA as the most frequent serologic finding [25]. Thrombocytopenia is a common finding in MDS, and can be seen in up to two third of the patients. In a study of 54 MDS patients with no treatment of transfusions, direct platelet immunofluorescence test for platelet associated IgG was positive in 28 patients. Patients with higher amount of platelet associated IgG, had significantly higher mean platelet volume (MPV), thrombocytopenia and worse outcome [63].
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4. Prognosis
\n
It has been suggested that appearance of skin vasculitis in MDS patients may reflect acute myeloid leukemia transformation. In a prospective study of 157 MDS patients for a median of 44 months, 15 patients (9.55%) experienced skin lesions, and neutrophilic dermatosis (7, 4.46%), specific lesions (5, 3.18%), cutaneous vasculitis (2, 1.27%) and Behçet’s disease (1, 0.63%) were reported. This study revealed that neutrophilic dermatosis was more prevalent in MDS patients, may confer the higher risk of acute myeloid leukemia transformation [64]. In another study of 84 newly diagnosed MDS patients, correlation of cutaneous findings with immunologic parameters and prognostic features of MDS examined, and revealed that 21 patients had skin lesions at presentation, and skin manifestations were a significant predictor of the high-risk MDS subgroup [65].
\n
In a retrospective study of 153 MDS patients, 12% had autoimmune diseases, and 63% has at least one immunological abnormality in test results. In this study, the survival of patients without autoimmune diseases was better than patients with autoimmune disease [66]. However, in a 4 year prospective study of 70 MDS patients, 53 patients without and 13 patients with autoimmune disease, there was no particular difference concerning prognosis between two groups. And patients with autoimmune diseases were not statistically different in survival compared with MDS patients without autoimmune disease [67].
\n
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5. Treatment
\n
Autoimmune disorders associated with MDS may predate or occur after MDS diagnosis, and their treatment many be associated with significant side effects in MDS patients. It has been recognized from several case reports that treatment of the underlying MDS may resolve the associated autoimmune disorders. In a transfusion dependent MDS patient who was receiving G-CSF and erythropoietin, neutrophilic dermatosis did not improve with G-CSF withholding. Two months after starting 5-azacitidine, a hypomethylating agent, the skin rash completely resolved, and did not recur after 2 years [68]. In another case series of 3 MDS patients with autoimmune disorders, 5-azacitidine improved both MDS and autoimmune disorders although long term steroid could not be tapered [69].
\n
In a retrospective study of 123 MDS patients with autoimmune disorders, 118 patients (96%) were treated with steroids, and 48% of patients were required a second line treatment for refractory disease or relapse. Although autoimmune disorder treatment did not improve MDS, MDS treatment with 5-azacitidine improved the autoimmune disorder in 9 out of 11 (80%) of patients [70]. In another retrospective study of 123 MDS/CMML patients with autoimmune disorders, 28 patients received at least 5 cycles of azacitidine, 20 of them did not respond to steroids. In 86% of MDS/CMML patients, clinical autoimmune syndromes improved by azacitidine, and prednisone dose tapered in 64% of patients [71].
\n
The overall effect of biologic medications efficacy in MDS patients who presented with autoimmune disorder is not clear. As of today, there is only one retrospective study of MDS patients with autoimmune disorders and biologic medications. In this study of at least one biologic medication, 29 patients followed for at least 3 years. 89% of patients received a biologic after failure or intolerance of two disease modifying anti rheumatic agents (DMARDs), however, 11% of patients received biologics as a first line treatment. Except rituximab, a CD-20 blocker, mainly for vasculitis (58% response), there was partial or insufficient response to TNF-α antagonists, and their efficacy is much less in autoimmune disorders associated with MDS than autoimmune disorders without MDS. Overall, response rate to 5-azacitidine in MDS-associated autoimmune disorders was 67% in favor of a causality relationship between MDS and autoimmune disorders [72].
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6. Conclusion
\n
Myelodysplastic syndromes are a heterogeneous group of progressive clonal hematopoietic stem cell disorders characterized by a varying degree of peripheral cytopenia, and increased probability of transformation to acute myeloid leukemia. MDS and particularly CMML are frequently associated with a variety of autoimmune disorders that can be diagnosed concomitantly with MDS or before or after MDS. The heterogeneity and complexity of pathology, clinical manifestations, response to therapy, and prognosis of MDS and its immune dysregulation makes the prognosis of MDS with autoimmune diseases a matter of debate. Prospective, randomized studies are required to confirm the autoimmune diseases role in MDS prognosis.
\n
\n
Acknowledgments
\n
The authors would like to thank Mr. Dixon Bennet for his technical assistance.
\n
\n
Disclosure
\n
None.
\n
\n',keywords:"autoimmune disorders (ADs), myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), Behçet’s disease, systemic lupus erythematosus (SLE), azathioprine, azacitidine, tumor necrosis factor alpha (TNF-α), regulatory T-cells (Treg), autoimmune hemolytic anemia (AIHA), vasculitis, chronic inflammatory demyelinating polyneuropathy (CIDP), neutrophilic dermatosis, Henoch-Schonlein purpura, relapsing polychondritis (RP), granulomatosis with polyangiitis (GPA), giant cell arteritis (GCA), polyarteritis nodosa (PAN)",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/63270.pdf",chapterXML:"https://mts.intechopen.com/source/xml/63270.xml",downloadPdfUrl:"/chapter/pdf-download/63270",previewPdfUrl:"/chapter/pdf-preview/63270",totalDownloads:1217,totalViews:302,totalCrossrefCites:0,dateSubmitted:"April 10th 2018",dateReviewed:"August 4th 2018",datePrePublished:"November 5th 2018",datePublished:"February 20th 2019",dateFinished:"August 28th 2018",readingETA:"0",abstract:"Myelodysplastic syndromes are heterogeneous group of clonal hematologic malignancies characterized by peripheral blood cytopenias secondary to the ineffective hematopoiesis. ADs are frequently reported in MDS, the incidence ranging from 10 to 30%, and particularly ADs are more frequently seen at CMML. ADs may prone patient to MDS, especially when immune suppressors such as azathioprine are used for the underlying AD. Both innate and adaptive immune systems, and different cytokines including interleukins, TNF-α, and C-X-C motif chemokine 10 (CXCL10) contribute in immune dysregulation of MDS. Vasculitis, seronegative rheumatoid arthritis, SLE, Behçet’s disease, RP, and AIHA are just some of the ADs occurring concomitantly with MDS. Although hematopoietic growth factors are recommended by the American Society of Clinical Oncology (ASCO), it has been recognized from several case reports that treatment of the underlying MDS may resolve the associated autoimmune disorders. The heterogeneity and complexity of pathology, clinical manifestations, response to therapy, and prognosis of MDS and its immune dysregulation make the prognosis of MDS with autoimmune diseases a matter of debate. Better understanding of the immune dysregulation of MDS in the molecular level may help to design prospective, double blind clinical trials to find the best treatment options for autoimmune disorders associated with MDS.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/63270",risUrl:"/chapter/ris/63270",signatures:"Kam A. Newman, Mojtaba Akhtari and Sheda Heidarian",book:{id:"7138",type:"book",title:"Recent Developments in Myelodysplastic Syndromes",subtitle:null,fullTitle:"Recent Developments in Myelodysplastic Syndromes",slug:"recent-developments-in-myelodysplastic-syndromes",publishedDate:"February 20th 2019",bookSignature:"Ota Fuchs",coverURL:"https://cdn.intechopen.com/books/images_new/7138.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-78985-478-7",printIsbn:"978-1-78985-477-0",pdfIsbn:"978-1-83962-040-9",isAvailableForWebshopOrdering:!0,editors:[{id:"36468",title:"Dr.",name:"Ota",middleName:null,surname:"Fuchs",slug:"ota-fuchs",fullName:"Ota Fuchs"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"253996",title:"Dr.",name:"Kam A.",middleName:null,surname:"Newman",fullName:"Kam A. Newman",slug:"kam-a.-newman",email:"knewman2@emc.org",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Eisenhower Medical Center",institutionURL:null,country:{name:"United States of America"}}},{id:"264133",title:"Dr.",name:"Mojtaba",middleName:null,surname:"Akhtari",fullName:"Mojtaba Akhtari",slug:"mojtaba-akhtari",email:"mojtaba.akhtari@med.usc.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"264161",title:"Dr.",name:"Sheda",middleName:null,surname:"Heidarian",fullName:"Sheda Heidarian",slug:"sheda-heidarian",email:"SHeidarian@Eisenhowerhealth.org",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. Rheumatologic manifestations of MDS",level:"1"},{id:"sec_3",title:"3. Autoimmune disorders in myelodysplastic syndrome",level:"1"},{id:"sec_3_2",title:"3.1. Vasculitis",level:"2"},{id:"sec_4_2",title:"3.2. Behçet’s disease",level:"2"},{id:"sec_5_2",title:"3.3. Inflammatory arthritis",level:"2"},{id:"sec_6_2",title:"3.4. Miscellaneous",level:"2"},{id:"sec_7_2",title:"3.5. Immunological abnormalities",level:"2"},{id:"sec_9",title:"4. Prognosis",level:"1"},{id:"sec_10",title:"5. Treatment",level:"1"},{id:"sec_11",title:"6. Conclusion",level:"1"},{id:"sec_12",title:"Acknowledgments",level:"1"},{id:"sec_12",title:"Disclosure",level:"1"}],chapterReferences:[{id:"B1",body:'Newman K, Maness-Harris L, El-Hemaidi I, Akhtari M. Revisiting use of growth factors in myelodysplastic syndromes. Asian Pacific Journal of Cancer Prevention. 2012;13(4):1081-1091\n'},{id:"B2",body:'Sallman DA, Tanaka TN, List A, Bejar R. SOHO state of the art update and next questions: Biology and treatment of myelodysplastic syndromes. 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Clinical Nuclear Medicine. 2016;41(8):e392-e393\n'},{id:"B51",body:'Esatoglu SN, Hatemi G, Salihoglu A, Hatemi I, Soysal T, Celik AF. A reappraisal of the association between Behçet\'s disease, myelodysplastic syndrome and the presence of trisomy 8: A systematic literature review. Clinical and Experimental Rheumatology. 2015;33(6 Supp. 94):S145-S151\n'},{id:"B52",body:'George SW, Newman ED. Seronegative inflammatory arthritis in the myelodysplastic syndromes. Seminars in Arthritis and Rheumatism. 1992;21(6):345-354\n'},{id:"B53",body:'Mekinian A, Braun T, Decaux O, Falgarone G, Toussirot E, Raffray L, et al. Inflammatory arthritis in patients with myelodysplastic syndromes: A multicenter retrospective study and literature review of 68 cases. Medicine (Baltimore). 2014;93(1):1-10\n'},{id:"B54",body:'Salahuddin N, Libman BS, Lunde JH, Kay J, Cooper SM. The association of relapsing polychondritis and myelodysplastic syndrome: Report of three cases. Journal of Clinical Rheumatology. 2000;6(3):146-149\n'},{id:"B55",body:'Van Besien K, Tricot G, Hoffman R. Relapsing polychondritis: A paraneoplastic syndrome associated with myelodysplastic syndromes. American Journal of Hematology. 1992;40(1):47-50\n'},{id:"B56",body:'Diebold L, Rauh G, Jäger K, Löhrs U. Bone marrow pathology in relapsing polychondritis: High frequency of myelodysplastic syndromes. British Journal of Haematology. 1995;89(4):820-830\n'},{id:"B57",body:'Oren H, Uçar C, Gülen H, Duman M, Irken G. Autoimmune hemolytic anemia occurring with myelodysplastic syndrome: Report of a pediatric case and review of the literature. Annals of Hematology. 2001;80(9):540-542\n'},{id:"B58",body:'Lin JT, Wang WS, Yen CC, Chiou TJ, Liu JH, Hsiao LT, et al. Myelodysplastic syndrome complicated by autoimmune hemolytic anemia: Remission of refractory anemia following mycophenolate mofetil. Annals of Hematology. 2002;81(12):723-726\n'},{id:"B59",body:'Sokol RJ, Hewitt S, Booker DJ. Erythrocyte autoantibodies, autoimmune haemolysis, and myelodysplastic syndromes. Journal of Clinical Pathology. 1989;42(10):1088-1091\n'},{id:"B60",body:'Ng HS, Ng HW, Sinniah R, Feng PH. A case of systemic lupus erythematosus with sideroblastic anaemia terminating in erythroleukaemia. Annals of the Rheumatic Diseases. 1981;40(4):422-426\n'},{id:"B61",body:'Jiménez-Balderas FJ, Morales-Polanco MR, Gutierrez L. Acute sideroblastic anemia in active systemic lupus erythematosus. Lupus. 1994;3(3):157-159\n'},{id:"B62",body:'Montoro J, Gallur L, Merchán B, Molero A, Roldán E, Martínez-Valle F, Villacampa G, Navarrete M, Ortega M, Castellví J, Saumell S, Bobillo S, Bosch F, Valcárcel D. Autoimmune disorders are common in myelodysplastic syndrome patients and confer an adverse impact on outcomes. Ann Hematol. 2018;97(8):1349-1356\n'},{id:"B63",body:'Gilli SC, de Souza Medina S, de Castro V, Fernandes LG, Saad ST. Platelet associated IgG may be related with thrombocytopenia in patients with myelodysplastic syndromes. Leukemia Research. 2012;36(5):554-559\n'},{id:"B64",body:'Farah C, Bulai Livideanu C, Jegu J, Paul C, Viraben R, Lamant L, et al. Prevalence and prognostic value of cutaneous manifestations in patients with myelodysplastic syndrome. Journal of the European Academy of Dermatology and Venereology. 2010;24(10):1171-1175\n'},{id:"B65",body:'Dalamaga M, Karmaniolas K, Matekovits A, Migdalis I, Papadavid E. Cutaneous manifestations in relation to immunologic parameters in a cohort of primary myelodysplastic syndrome patients. Journal of the European Academy of Dermatology and Venereology. 2008;22(5):543-548\n'},{id:"B66",body:'Okamoto T, Okada M, Mori A, Saheki K, Takatsuka H, Wada H, et al. Correlation between immunological abnormalities and prognosis in myelodysplastic syndrome patients. International Journal of Hematology. 1997;66(3):345-351\n'},{id:"B67",body:'Giannouli S, Voulgarelis M, Zintzaras E, Tzioufas AG, Moutsopoulos HM. Autoimmune phenomena in myelodysplastic syndromes: A 4-yr prospective study. Rheumatology (Oxford, England). 2004;43(5):626-632\n'},{id:"B68",body:'Raj K, Ho A, Creamer JD, du Vivier AW, Salisbury JR, Mufti GJ. Complete response of deep neutrophilic dermatosis associated with myelodysplastic syndrome to 5-azacytidine. The British Journal of Dermatology. 2007;156(5):1039-1041\n'},{id:"B69",body:'Pilorge S, Doleris LM, Dreyfus F, Park S. The autoimmune manifestations associated with myelodysplastic syndrome respond to 5-azacytidine: A report on three cases. British Journal of Haematology. 2011;153(5):664-665\n'},{id:"B70",body:'Mekinian A, Grignano E, Braun T, Decaux O, Liozon E, Costedoat-Chalumeau N, et al. Systemic inflammatory and autoimmune manifestations associated with myelodysplastic syndromes and chronic myelomonocytic leukaemia: A French multicentre retrospective study. Rheumatology (Oxford, England). 2016;55(2):291-300\n'},{id:"B71",body:'Fraison JB, Mekinian A, Grignano E, Kahn JE, Arlet JB, Decaux O, et al. Efficacy of Azacitidine in autoimmune and inflammatory disorders associated with myelodysplastic syndromes and chronic myelomonocytic leukemia. Leukemia Research. 2016;43:13-17\n'},{id:"B72",body:'Mekinian A, Dervin G, Lapidus N, Kahn JE, Terriou L, Liozon E, et al. GFM, SNFMI, CRI and MINHEMON. Biologics in myelodysplastic syndrome-related systemic inflammatory and autoimmune diseases: French multicenter retrospective study of 29 patients. Autoimmunity Reviews. 2017;16(9):903-910\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Kam A. Newman",address:"knewman@eisenhowerhealth.org",affiliation:'
Eisenhower Rheumatology Specialty Clinic, Eisenhower Health, Internal Medicine Residency Program, Mike and Jan Salta Health Center, United States
President Elect, Medical Staff, Eisenhower Health, United States
'}],corrections:null},book:{id:"7138",type:"book",title:"Recent Developments in Myelodysplastic Syndromes",subtitle:null,fullTitle:"Recent Developments in Myelodysplastic Syndromes",slug:"recent-developments-in-myelodysplastic-syndromes",publishedDate:"February 20th 2019",bookSignature:"Ota Fuchs",coverURL:"https://cdn.intechopen.com/books/images_new/7138.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-78985-478-7",printIsbn:"978-1-78985-477-0",pdfIsbn:"978-1-83962-040-9",isAvailableForWebshopOrdering:!0,editors:[{id:"36468",title:"Dr.",name:"Ota",middleName:null,surname:"Fuchs",slug:"ota-fuchs",fullName:"Ota Fuchs"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},profile:{item:{id:"199455",title:"Dr.",name:"Jonathan",middleName:null,surname:"Cueto-Escobedo",email:"jcueto@uv.mx",fullName:"Jonathan Cueto-Escobedo",slug:"jonathan-cueto-escobedo",position:null,biography:"Jonathan Cueto-Escobedo received his doctorate degree in Psychology (Behavioral Neuroscience) from the Universidad Nacional Autónoma de México. He is currently a researcher at the Institute of Health Sciences, Universidad Veracruzana and a member of the National System of Investigators (SNI I). His research interests include experimental models of anxiety and depression, neurobiology of behavior, particularly addiction and food intake as a reward with a translational perspective. He has published 10 book chapters and 13 scientific papers and made more than 20 presentations at international conferences. He has also published several works of science divulgation. He has lectured at several universities in México, including the University of Xalapa, University of Veracruz, University of Guadalajara, University of Tlaxcala, and Universidad Nacional Autónoma de México.",institutionString:"Institute of Neuroetology, University of Veracruz",profilePictureURL:"https://mts.intechopen.com/storage/users/199455/images/system/199455.jpeg",totalCites:0,totalChapterViews:"0",outsideEditionCount:0,totalAuthoredChapters:"3",totalEditedBooks:"0",personalWebsiteURL:null,twitterURL:null,linkedinURL:null,institution:null},booksEdited:[],chaptersAuthored:[{id:"56413",title:"Introductory Chapter: A Multidisciplinary Look at Menopause",slug:"introductory-chapter-a-multidisciplinary-look-at-menopause",abstract:null,signatures:"Juan Francisco Rodríguez‐Landa and Jonathan Cueto‐Escobedo",authors:[{id:"45702",title:"Dr.",name:"Juan Francisco",surname:"Rodríguez-Landa",fullName:"Juan Francisco Rodríguez-Landa",slug:"juan-francisco-rodriguez-landa",email:"juarodriguez@uv.mx"},{id:"199455",title:"Dr.",name:"Jonathan",surname:"Cueto-Escobedo",fullName:"Jonathan Cueto-Escobedo",slug:"jonathan-cueto-escobedo",email:"jcueto@uv.mx"}],book:{id:"5984",title:"Menopause",slug:"a-multidisciplinary-look-at-menopause",productType:{id:"1",title:"Edited Volume"}}},{id:"58763",title:"Stress in Nursing University Students and Mental Health",slug:"stress-in-nursing-university-students-and-mental-health",abstract:"Stress is a physiological response that impacts the cognitive, emotional, behavioral, and social components. It also involves the adaptation of the organism, the coping resources, and the environment. In young people, stress can be triggered by social interactions or school requirements. This chapter is a narrative review analyzing scientific bibliography from the main databases (NIH, Scielo, Redalyc) that explored the main stressors and their effects on nursing students. These stressors include the care of patients, assignments and workloads, academic evaluations, and negative or hostile social interactions. Data include the deleterious effects of stress in nursing students as anxiety, depression, inhibiting learning, and burnout, which negatively impact their academic development and health. Finally, some interventions to reduce the impact of stress are discussed. Conclusion: Stress responses in nursing students vary in duration and intensity during their academic training; final effects depend on the coping mechanisms, individual resources, and hospital environment. The effects of stress on nursing students impact on academic performance but could also trigger several psychiatric disorders as depression or anxiety, as well as other associated problems such as sleep disorders, alcohol, and psychoactive drug consumption, which in the short and long term may affect the patient care.",signatures:"Frank Pulido-Criollo, Jonathan Cueto-Escobedo and Gabriel Guillén-\nRuiz",authors:[{id:"199455",title:"Dr.",name:"Jonathan",surname:"Cueto-Escobedo",fullName:"Jonathan Cueto-Escobedo",slug:"jonathan-cueto-escobedo",email:"jcueto@uv.mx"},{id:"175891",title:"MSc.",name:"Frank",surname:"Pulido-Criollo",fullName:"Frank Pulido-Criollo",slug:"frank-pulido-criollo",email:"fpulido@unpa.edu.mx"},{id:"218681",title:"Dr.",name:"Gabriel",surname:"Guillén-Ruiz",fullName:"Gabriel Guillén-Ruiz",slug:"gabriel-guillen-ruiz",email:"gguillen@uv.mx"}],book:{id:"6225",title:"Health and Academic Achievement",slug:"health-and-academic-achievement",productType:{id:"1",title:"Edited Volume"}}},{id:"73245",title:"New Developments in Behavioral Pharmacology",slug:"new-developments-in-behavioral-pharmacology",abstract:"Behavioral pharmacology research has been a cornerstone in the understanding of the processes that underlie the behavior of living organisms as well as the biological basis of the behavioral, emotional, and cognitive disorders that affect humans. The findings in this area have helped to explore the potential therapeutic effects of several substances for the treatment of the mentioned disorders. The present chapter brings an extremely brief introduction to this vast area. First, we try to put in context behavioral pharmacology and its relevance and then show some brief examples of how this discipline has developed over the years. Second, we review the concept of a “research model” in preclinical behavioral pharmacology, given the importance of animal models and tests in this area, followed by a brief review of the recent advances using zebra fish as a valuable tool of research. Third, more specific examples are aborded, such as the findings on sleep disorders and those related to sexual hormones and menopause.",signatures:"Jonathan Cueto-Escobedo, Fabio García-García, Caio Maximino and Juan Francisco Rodríguez-Landa",authors:[{id:"45702",title:"Dr.",name:"Juan Francisco",surname:"Rodríguez-Landa",fullName:"Juan Francisco Rodríguez-Landa",slug:"juan-francisco-rodriguez-landa",email:"juarodriguez@uv.mx"},{id:"199455",title:"Dr.",name:"Jonathan",surname:"Cueto-Escobedo",fullName:"Jonathan Cueto-Escobedo",slug:"jonathan-cueto-escobedo",email:"jcueto@uv.mx"},{id:"108955",title:"Dr.",name:"Fabio",surname:"García-García",fullName:"Fabio García-García",slug:"fabio-garcia-garcia",email:"fgarcia@uv.mx"},{id:"329483",title:"Ph.D.",name:"Caio",surname:"Maximino",fullName:"Caio Maximino",slug:"caio-maximino",email:"cmaximino@unifesspa.edu.br"}],book:{id:"7882",title:"Behavioral Pharmacology",slug:"behavioral-pharmacology-from-basic-to-clinical-research",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"174651",title:"Dr.",name:"Abraham",surname:"Puga-Olguín",slug:"abraham-puga-olguin",fullName:"Abraham Puga-Olguín",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"188289",title:"Prof.",name:"Sylvia",surname:"Kirchengast",slug:"sylvia-kirchengast",fullName:"Sylvia Kirchengast",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Vienna",institutionURL:null,country:{name:"Austria"}}},{id:"203535",title:"M.Sc.",name:"Simoni",surname:"Bittar",slug:"simoni-bittar",fullName:"Simoni Bittar",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Federal University of Paraíba",institutionURL:null,country:{name:"Brazil"}}},{id:"203538",title:"Mr.",name:"Elisio",surname:"Pereira Neto",slug:"elisio-pereira-neto",fullName:"Elisio Pereira Neto",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"206112",title:"MSc.",name:"Janine",surname:"Padilha",slug:"janine-padilha",fullName:"Janine Padilha",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"206113",title:"Mrs.",name:"Hidayane",surname:"Dias",slug:"hidayane-dias",fullName:"Hidayane Dias",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"206114",title:"Mr.",name:"Patrick",surname:"Pfeiffer",slug:"patrick-pfeiffer",fullName:"Patrick Pfeiffer",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"206115",title:"Mr.",name:"Wagner",surname:"Santos",slug:"wagner-santos",fullName:"Wagner Santos",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"206116",title:"Dr.",name:"Maria",surname:"Cirilo-Sousa",slug:"maria-cirilo-sousa",fullName:"Maria Cirilo-Sousa",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"206117",title:"MSc.",name:"José",surname:"Macêdo",slug:"jose-macedo",fullName:"José Macêdo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null}]},generic:{page:{slug:"attribution-policy",title:"Attribution Policy",intro:"
Definition of Terms:
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",metaTitle:"Attribution Policy",metaDescription:"DEFINITION OF TERMS",metaKeywords:null,canonicalURL:"/page/attribution-policy",contentRaw:'[{"type":"htmlEditorComponent","content":"
Work - a book Chapter (as well as Conference Papers), including any and all content, graphics, images and/or other materials forming part of, or accompanying, the Chapter/Conference Paper.
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Attribution – appropriate credit for the used Work or book.
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With the purpose of protecting Authors' copyright and the transparent reuse of OA (Open Access) content, IntechOpen has developed Rules of Attribution of Works licensed under Creative Commons licenses.
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All Chapters published in IntechOpen books prior to October 2011 are licensed under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported license (CC BY-NC-SA 3.0);
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All Chapters published in IntechOpen books after October 2011 are licensed under the Creative Commons Attribution 3.0 Unported license (CC BY 3.0);
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In case you reuse or republish any of the Works licensed under CC licenses, you must abide by the guidelines outlined below:
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1. Rules for reusing of books in their entirety or significant parts of books
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All rights to Books and other compilations published on the IntechOpen platform and in print are reserved by IntechOpen. The Copyright to Books and other compilations is subject to a separate Copyright from any that exists in the included Works.
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A Book in its entirety or a significant part of a Book cannot be translated freely without specific written consent by the publisher. Further information can be obtained at permissions@intechopen.com.
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In instances where permission is obtained from the publisher for reusing or republishing the Book, or significant parts of the Book, all of the following conditions apply:
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Information about the first publisher must be provided – please note the fact that the material was originally published by IntechOpen as an OA (Open Access) publication must be acknowledged;
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Since you are reusing content that someone else created and allowed you to use freely, you must credit all Authors involved;
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Any original Copyright Notices associated, with the Works which constitute the Book must be kept intact;
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Provision of the original title of the Book, as well as the original titles of any individual Works;
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Provision of the URL where the Book is hosted, with a notice to the effect that the Book is an OA (Open Access) publication;
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Provision of the URL to every individual Work which constitutes the Book with a notice that the Work is an OA (Open Access) publication. As the material has been accessed for free, it is incumbent upon you to provide the source so that others can also access it for free.
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Every single Work that is used has to be attributed in the way described. If you are unsure about proper attribution, please write to permissions@intechopen.com.
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Individual Works originally published in IntechOpen books are licensed under Creative Commons licenses and can be freely used under terms of the respective CC license, if properly attributed. In order to properly attribute the Work you must respect all the conditions outlined below:
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Credit all Authors – since you are reusing contents that someone created and allowed you to use freely, you have to acknowledge authorship;
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Provide information about the first publisher – please note the fact that the material was originally published by IntechOpen as an OA (Open Access) Work must be acknowledged.
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Every single Work that is used has to be attributed in the way as described. If you are unsure about proper attribution, please contact Us at permissions@intechopen.com.
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In the event that you use more than one of IntechOpen's Works published in one or more books (but not a significant part of the book that is under separate Copyright), each of these have to be properly attributed in the way described.
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IntechOpen does not have any claims on newly created copyrighted Works, but the Works originally published by IntechOpen must be properly attributed.
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All these rules apply to BOTH online and offline use.
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Parts of the Rules of Attribution are based on Work Attributing Creative Commons Materials published by the Australian Research Council Centre of Excellence for Creative Industries and Innovation, in partnership with Creative Commons Australia, which can be found at creativecommons.org.au licensed under Creative Commons Attribution 2.5 Australia license, and Best practices for attribution published by Creative Commons, which can be found at wiki.creativecommons.org under the Creative Commons Attribution 4.0 license.
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All the above rules are subject to change, IntechOpen reserves the right to take appropriate action if any of the conditions outlined above are not met.
Work - a book Chapter (as well as Conference Papers), including any and all content, graphics, images and/or other materials forming part of, or accompanying, the Chapter/Conference Paper.
\n\n
Attribution – appropriate credit for the used Work or book.
\n\n
Creative Commons licenses – enable licensors to retain copyright while allowing others to use their Works in an appropriate way.
\n\n
Rules of Attribution for Works Published by IntechOpen
\n\n
With the purpose of protecting Authors' copyright and the transparent reuse of OA (Open Access) content, IntechOpen has developed Rules of Attribution of Works licensed under Creative Commons licenses.
\n\n
\n\t
All Chapters published in IntechOpen books prior to October 2011 are licensed under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported license (CC BY-NC-SA 3.0);
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All Chapters published in IntechOpen books after October 2011 are licensed under the Creative Commons Attribution 3.0 Unported license (CC BY 3.0);
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In case you reuse or republish any of the Works licensed under CC licenses, you must abide by the guidelines outlined below:
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1. Rules for reusing of books in their entirety or significant parts of books
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All rights to Books and other compilations published on the IntechOpen platform and in print are reserved by IntechOpen. The Copyright to Books and other compilations is subject to a separate Copyright from any that exists in the included Works.
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A Book in its entirety or a significant part of a Book cannot be translated freely without specific written consent by the publisher. Further information can be obtained at permissions@intechopen.com.
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In instances where permission is obtained from the publisher for reusing or republishing the Book, or significant parts of the Book, all of the following conditions apply:
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Information about the first publisher must be provided – please note the fact that the material was originally published by IntechOpen as an OA (Open Access) publication must be acknowledged;
\n\t
All original Academic Editor(s) must be credited;
\n\t
Since you are reusing content that someone else created and allowed you to use freely, you must credit all Authors involved;
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The type of license that is available for the Works must be indicated, as well as a link to the license provided, so that others can investigate the terms of the license. You will be aware that the material can be used for free in consequence of the CC license attribution, so you must acknowledge that fact. It is not sufficient that the material is Creative Commons, because that says nothing about how the material can actually be used. There are different CC licenses and you have to identify the specific license that is being used;
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Any original Copyright Notices associated, with the Works which constitute the Book must be kept intact;
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Provision of the original title of the Book, as well as the original titles of any individual Works;
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Provision of the URL where the Book is hosted, with a notice to the effect that the Book is an OA (Open Access) publication;
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Provision of the URL to every individual Work which constitutes the Book with a notice that the Work is an OA (Open Access) publication. As the material has been accessed for free, it is incumbent upon you to provide the source so that others can also access it for free.
\n
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Every single Work that is used has to be attributed in the way described. If you are unsure about proper attribution, please write to permissions@intechopen.com.
\n\n
2. Rules of attribution for works published by IntechOpen
\n\n
Individual Works originally published in IntechOpen books are licensed under Creative Commons licenses and can be freely used under terms of the respective CC license, if properly attributed. In order to properly attribute the Work you must respect all the conditions outlined below:
\n\n
\n\t
Credit all Authors – since you are reusing contents that someone created and allowed you to use freely, you have to acknowledge authorship;
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Indicate the type of license under which the Work is available and provide the URL to the license so others can find out the license terms. Preferably keep intact any original Copyright Notice associated with the Chapter (if any). You will be aware that the material can be used for free in consequence of the CC license attribution, so you must acknowledge that fact. It is not sufficient that the material is Creative Commons, because that says nothing about how the material can actually be used. There are different CC licenses and you have to identify the specific license that is being used;
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Provide the URL where the Work is hosted, preferably providing the original title of the Work, as well as the original title of the Book with a notification that the Work is an OA (Open Access) publication. As the material has been accessed for free, it is incumbent upon you to provide the source so that others can also access it for free;
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Provide information about the first publisher – please note the fact that the material was originally published by IntechOpen as an OA (Open Access) Work must be acknowledged.
\n
\n\n
Every single Work that is used has to be attributed in the way as described. If you are unsure about proper attribution, please contact Us at permissions@intechopen.com.
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In the event that you use more than one of IntechOpen's Works published in one or more books (but not a significant part of the book that is under separate Copyright), each of these have to be properly attributed in the way described.
\n\n
IntechOpen does not have any claims on newly created copyrighted Works, but the Works originally published by IntechOpen must be properly attributed.
\n\n
All these rules apply to BOTH online and offline use.
\n\n
Parts of the Rules of Attribution are based on Work Attributing Creative Commons Materials published by the Australian Research Council Centre of Excellence for Creative Industries and Innovation, in partnership with Creative Commons Australia, which can be found at creativecommons.org.au licensed under Creative Commons Attribution 2.5 Australia license, and Best practices for attribution published by Creative Commons, which can be found at wiki.creativecommons.org under the Creative Commons Attribution 4.0 license.
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All the above rules are subject to change, IntechOpen reserves the right to take appropriate action if any of the conditions outlined above are not met.
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Policy last updated: 2016-06-09
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After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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Advancement in technology now ensures power storage and delivery from few seconds to days/months. But an effective management of the distributed energy resources and its storage systems is essential to ensure efficient operation and long service life. This chapter presents the issues faced in integrating renewables in DG and the growing necessity of energy storages. Types of energy storage systems (ESSs) and their applications have also been detailed. A brief literature study on energy management of ESSs in distributed microgrids has also been included. This is followed by a simple case study to illustrate the need and effect of management of ESSs in distributed systems.",book:{id:"5186",slug:"energy-management-of-distributed-generation-systems",title:"Energy Management of Distributed Generation Systems",fullTitle:"Energy Management of Distributed Generation Systems"},signatures:"Amjed Hina Fathima and Kaliannan Palanisamy",authors:[{id:"179143",title:"Dr.",name:"Hina",middleName:null,surname:"Fathima",slug:"hina-fathima",fullName:"Hina Fathima"},{id:"185245",title:"Dr.",name:"Kaliannan",middleName:null,surname:"Palanisamy",slug:"kaliannan-palanisamy",fullName:"Kaliannan Palanisamy"}]},{id:"29291",doi:"10.5772/31112",title:"Electrolyte and Solid-Electrolyte Interphase Layer in Lithium-Ion Batteries",slug:"electrolyte-and-solid-electrolyte-interphase-layer-in-lithium-ion-batteries",totalDownloads:8845,totalCrossrefCites:3,totalDimensionsCites:20,abstract:null,book:{id:"848",slug:"lithium-ion-batteries-new-developments",title:"Lithium Ion Batteries",fullTitle:"Lithium Ion Batteries - New Developments"},signatures:"Alexandre Chagnes and Jolanta Swiatowska",authors:[{id:"85632",title:"Dr.",name:"Alexandre",middleName:null,surname:"Chagnes",slug:"alexandre-chagnes",fullName:"Alexandre Chagnes"},{id:"88217",title:"Dr.",name:"Jolanta",middleName:null,surname:"Swiatowska",slug:"jolanta-swiatowska",fullName:"Jolanta Swiatowska"}]},{id:"50727",doi:"10.5772/63631",title:"Advanced Metering Infrastructure Based on Smart Meters in Smart Grid",slug:"advanced-metering-infrastructure-based-on-smart-meters-in-smart-grid",totalDownloads:4277,totalCrossrefCites:16,totalDimensionsCites:19,abstract:"Due to lack of situational awareness, automated analysis, poor visibility, and mechanical switches, today's electric power grid has been aging and ill‐suited to the demand for electricity, which has gradually increased, in the twenty‐first century. Besides, the global climate change and the greenhouse gas emissions on the Earth caused by the electricity industries, the growing population, one‐way communication, equipment failures, energy storage problems, the capacity limitations of electricity generation, decrease in fossil fuels, and resilience problems put more stress on the existing power grid. Consequently, the smart grid (SG) has emerged to address these challenges. To realize the SG, an advanced metering infrastructure (AMI) based on smart meters is the most important key.",book:{id:"5119",slug:"smart-metering-technology-and-services-inspirations-for-energy-utilities",title:"Smart Metering Technology and Services",fullTitle:"Smart Metering Technology and Services - Inspirations for Energy Utilities"},signatures:"Trong Nghia Le, Wen‐Long Chin, Dang Khoa Truong and Tran Hiep\nNguyen",authors:[{id:"178015",title:"Dr.",name:"Trong Nghia",middleName:null,surname:"Le",slug:"trong-nghia-le",fullName:"Trong Nghia Le"},{id:"178169",title:"Prof.",name:"Wen-Long",middleName:null,surname:"Chin",slug:"wen-long-chin",fullName:"Wen-Long Chin"}]},{id:"14085",doi:"10.5772/14798",title:"Magnetic Reluctance Method for Dynamical Modeling of Squirrel Cage Induction Machines",slug:"magnetic-reluctance-method-for-dynamical-modeling-of-squirrel-cage-induction-machines",totalDownloads:5337,totalCrossrefCites:13,totalDimensionsCites:15,abstract:null,book:{id:"69",slug:"electric-machines-and-drives",title:"Electric Machines and Drives",fullTitle:"Electric Machines and Drives"},signatures:"Jalal Nazarzadeh and Vahid Naeini",authors:[{id:"18796",title:"Prof.",name:"Jalal",middleName:null,surname:"Nazarzadeh",slug:"jalal-nazarzadeh",fullName:"Jalal Nazarzadeh"},{id:"20586",title:"Prof.",name:"Vahid",middleName:null,surname:"Naeini",slug:"vahid-naeini",fullName:"Vahid Naeini"}]}],mostDownloadedChaptersLast30Days:[{id:"77871",title:"Protection of Microgrids",slug:"protection-of-microgrids",totalDownloads:279,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The concept of microgrids goes back to the early years of the electricity industry although the systems then were not formally called microgrids. 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An example with simulations carried out in the IPSA simulation platform was used to explain different protection requirements and calculation procedures. Finally, grounding requirements are discussed while referring to different interfacing transformer connections and voltage source inverter connections.",book:{id:"10176",slug:"microgrids-and-local-energy-systems",title:"Microgrids and Local Energy Systems",fullTitle:"Microgrids and Local Energy Systems"},signatures:"Janaka Ekanayake",authors:[{id:"328170",title:"Prof.",name:"Janake",middleName:null,surname:"Ekanayake",slug:"janake-ekanayake",fullName:"Janake Ekanayake"}]},{id:"79509",title:"Power Electronic Converters for Microgrids",slug:"power-electronic-converters-for-microgrids",totalDownloads:259,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Power electronic converters are indispensable building blocks of microgrids. They are the enabling technology for many applications of microgrids, e.g., renewable energy integration, transportation electrification, energy storage, and power supplies for computing. In this chapter, the requirements, functions, and operation of power electronic converters are introduced. Then, different topologies of the converters used in microgrids are discussed, including DC/DC converters, single-phase DC/AC converters, three-phase three-wire, and four-wire DC/AC converters. The remaining parts of this chapter focus on how to optimally design and control these converters with the emerging wide-bandgap semiconductors. 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This new technology can be used in various wireless power transfer applications with different specifications, necessities, and restrictions such as in electric vehicles and consumer electronics. A typical ICWPT system involves a loosely coupled magnetic coupling structure and power electronics circuitries as an integrated system. In this chapter, the emphasis is placed on the magnetic coupling structure, which is the most important part of the system. Although this technology has motivated considerable research and development in the past two decades, still there are several theoretical studies such as the level of the operating frequency, operating at high secondary circuit quality factor, coupling efficiency, etc., that need further investigation to fully develop the governing mathematical relationships of this technology.",book:{id:"5187",slug:"wireless-power-transfer-fundamentals-and-technologies",title:"Wireless Power Transfer",fullTitle:"Wireless Power Transfer - Fundamentals and Technologies"},signatures:"Ali Abdolkhani",authors:[{id:"179618",title:"Dr.",name:"Ali",middleName:null,surname:"Abdolkhani",slug:"ali-abdolkhani",fullName:"Ali Abdolkhani"}]},{id:"78626",title:"Electricity Storage in Local Energy Systems",slug:"electricity-storage-in-local-energy-systems",totalDownloads:211,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Traditionally, power system operation has relied on supply side flexibility from large fossil-based generation plants to managed swings in supply and/or demand. An increase in variable renewable generation has increased curtailment of renewable electricity and variations in electricity prices. Consumers can take advantage of volatile electricity prices and reduce their bills using electricity storage. With reduced fossil-based power generation, traditional methods for balancing supply and demand must change. Electricity storage offers an alternative to fossil-based flexibility, with an increase expected to support high levels of renewable generation. Electrochemical storage is a promising technology for local energy systems. In particular, lithium-ion batteries due to their high energy density and high efficiency. However, despite their 89% decrease in capital cost over the last 10 years, lithium-ion batteries are still relatively expensive. Local energy systems with battery storage can use their battery for different purposes such as maximising their self-consumption, minimising their operating cost through energy arbitrage which is storing energy when the electricity price is low and releasing the energy when the price increases, and increasing their revenue by providing flexibility services to the utility grid. Power rating and energy capacity are vitally important in the design of an electricity storage system. A case study is given for the purpose of providing a repeatable methodology for optimally sizing of a battery storage system for a local energy system. 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He also has an honorary appointment to serve as a Collaborative Professor at Kanazawa University, Japan, from Mar 2015 to the present. \nFormerly, Dr. Rahman was a faculty member of the University of Chittagong, Bangladesh, affiliated with the Department of Chemistry (Oct 2002 to Mar 2012) and the Department of Applied Chemistry and Chemical Engineering (Mar 2012 to Sep 2015). Dr. Rahman was also adjunctly attached with Kanazawa University, Japan (Visiting Research Professor, Dec 2014 to Mar 2015; JSPS Postdoctoral Research Fellow, Apr 2012 to Mar 2014), and Tokyo Institute of Technology, Japan (TokyoTech-UNESCO Research Fellow, Oct 2004–Sep 2005). \nHe received his Ph.D. degree in Environmental Analytical Chemistry from Kanazawa University, Japan (2011). He also achieved a Diploma in Environment from the Tokyo Institute of Technology, Japan (2005). Besides, he has an M.Sc. degree in Applied Chemistry and a B.Sc. degree in Chemistry, all from the University of Chittagong, Bangladesh. \nDr. Rahman’s research interest includes the study of the fate and behavior of environmental pollutants in the biosphere; design of low energy and low burden environmental improvement (remediation) technology; implementation of sustainable waste management practices for treatment, handling, reuse, and ultimate residual disposition of solid wastes; nature and type of interactions in organic liquid mixtures for process engineering design applications.",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"201020",title:"Dr.",name:"Zinnat Ara",middleName:null,surname:"Begum",slug:"zinnat-ara-begum",fullName:"Zinnat Ara Begum",profilePictureURL:"https://mts.intechopen.com/storage/users/201020/images/system/201020.jpeg",biography:"Zinnat A. Begum received her Ph.D. in Environmental Analytical Chemistry from Kanazawa University in 2012. She achieved her Master of Science (M.Sc.) degree with a major in Applied Chemistry and a Bachelor of Science (B.Sc.) in Chemistry, all from the University of Chittagong, Bangladesh. Her work affiliations include Fukushima University, Japan (Visiting Research Fellow, Institute of Environmental Radioactivity: Mar 2016 to present), Southern University Bangladesh (Assistant Professor, Department of Civil Engineering: Jan 2015 to present), and Kanazawa University, Japan (Postdoctoral Fellow, Institute of Science and Engineering: Oct 2012 to Mar 2014; Research fellow, Venture Business Laboratory, Advanced Science and Social Co-Creation Promotion Organization: Apr 2018 to Mar 2021). 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Graduate in Sciences (Chemist), graduate in Geography and History (Geography), master in Water Management, Treatment, master in Fertilizers and Environment and master in Environmental Management; Ph.D. in Environmental Sciences. His research is focused on soil-water and waste-environment relations, mainly on soil-water and soil-waste interactions under different management and waste reuse. His work is reflected in more than 230 communications presented in national and international conferences and congresses, 29 invited lectures from universities, associations and government agencies. 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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. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. 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. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. 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In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. 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Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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