Polysilicon mechanical properties data (Sharpe, 2001).
\r\n\tThis book aims to expose the recent advances in the research and development of chemical and biochemical processes to obtain bio-based chemical compounds and fuels from glycerol.
\r\n\r\n\tChapters dealing with the synthesis and characterization of catalysts (single and mixed hydroxides and oxides, supported catalysts, zeolites, heteropolyacids, pillared-clays, and metal-organic frameworks) and biocatalysts (novel microbial and fungi cultures, immobilized cells, immobilized enzymes, and nanobiocatalysts) to carry out the conversion of glycerol, as well as their testing in discontinuous and continuous stirred reactors, fixed-bed, fluidized-bed, trickle-bed, bubble column, airlift and membrane (bio)reactors are welcome.
\r\n\r\n\tThe book will comprise, but will not be limited to, the homogeneous and heterogeneous chemical reactions of glycerol such as dehydration, hydrogenolysis, partial oxidation, steam- and dry-reforming, glycerol to hydrocarbon fuels and aromatics, (trans)esterification, etherification, halogenation, ammoxidation, as well as supercritical, and photocatalytic processes.
\r\n\r\n\tAdditionally, we hope to cover the bioprocessing of glycerol, including microbial and fungal fermentation and enzymatic reactions to obtain C2-C4 alcohols, diols, hydrogen, methane, organic acids, dihydroxyacetone, biopolymers, and others.
\r\n\tThe book will also deal with the engineering aspects of glycerol processing, such as chemical equilibrium of glycerol reactions, reaction kinetics, (bio)reactor modeling, as well as process simulation and optimization of process variables and reactors.
The performance of micro electronic and mechanical systems (MEMS) strongly depends on the mechanical properties of materials used. The evaluation of the mechanical properties of MEMS materials is indispensable for designing MEMS devices. Accurate values of mechanical properties (elastic properties, internal stress, strength, fatigue) are necessary for obtaining the optimum performances. For an example, elastic properties are necessary in prediction of the amount of deflection from an applied force and material strength sets device operational limits. Also, in view of reliability and life time requirements, mechanical characterization of MEMS materials becomes increasingly important. Small size of MEMS devices often leads to their usage in harsh environments, and good knowledge of mechanical properties may lead to elimination of some of the mechanical failure modes through proper material selection, design, fabrication and packaging processes. As the interest in MEMS grows, the demand for applicable data increases. Reliability, accuracy and repeatability of evaluation methods also became an issue. However, MEMS use materials such as silicon and many other thin films that are not fully characterized regarding their mechanical properties because they had not previously been considered as mechanical materials. The properties of thin films have so far been evaluated mostly to satisfy demands in semiconductor device research, but evaluations were mainly focused on the electrical properties, while investigations of mechanical properties were limited mainly to internal stresses. For that reason, the bulk properties were adopted whenever mechanical properties were needed, but with the growing application of thin films in various mechanical structures grew the need for better understanding of their mechanical and electromechanical properties. Therefore mechanical properties of thin films used in MEMS need to be accurately evaluated – they should be measured at the same scale as micro- and nano-devices since they differ from bulk material properties. Thin-film and bulk materials usually have different compositions, phase and microstructure and the formation process for thin films must be taken into account (deposition, thermal treatment, implantation and oxidation). Mechanical processing as the processing method for most bulk structures is in case of thin films substituted with photolithography and etching. Also, bulk and thin film have different surface finishing of processed structures. When size effect is concerned, one must have in mind that the ratio of surface area to the volume increases as dimensions of a device decrease. The dimensions of structures in MEMS devices range from sub-micrometers to millimetres and therefore the size effect in thin films is more sensitive than in bulk materials. Many measurement methods have been developed for evaluation of mechanical properties of thin films and various values have been measured (Ammaleh, 2003; Dual, 2004; Yi, 1999). Reported variations in measured values were large requiring extensive research in order to evaluate repeatability, accuracy and data reliability of various measurement methods for mechanical properties of MEMS materials. Therefore, development of international standards on MEMS materials and their properties measurement methods is one of the primary tasks when MEMS technology is in question. For that reason, this chapter intends to give an overview of basic test methods and mechanical properties of MEMS materials. Definitions of mechanical properties of interest are presented along with current test methods for MEMS materials. Also, a summary of mechanical properties of various MEMS materials is given. Measured material data for MEMS structural materials is obtained from the literature. Finally, the brief overview of the topic is presented in the last section, pointing out the necessity of standardization of testing procedures that would accelerate advances in MEMS technology.
\n\t\tMEMS devices use materials such as silicon and many other thin films. These materials had not previously been considered mechanical materials and for that reason are not fully characterized regarding their mechanical properties. The evaluation of the mechanical properties of electrical materials forming MEMS devices is needed to provide the engineering base for full exploitation of the MEMS technology. It is essential both from the aspect of MEMS device performances, as well as from the reliability aspect. Mechanical properties of interest fall into three general categories: elastic, inelastic, and strength. In order to predict the amount of deflection from the applied force, or vice versa, the elastic properties of MEMS materials must be known. Inelastic material properties are important for ductile materials, when deformed structure does not return to its initial state. When defining operational limits of MEMS device, the strength of the material must be known. The key factor in manufacturing reliable MEMS devices is good understanding of the relation between the material properties and its processing. When studying material properties, measured values should be independent of test method and the size of the specimen. However, when MEMS devices are in question, the size of the specimen may affect the measurements. For that reason an extensive process should be initiated in defining test methods with adequate sensibility and repeatability that would provide accurate values of mechanical properties.
\n\t\t\tElastic properties are directly related to the device performance. Young’s modulus and Poisons ratio are basic elastic properties that govern the mechanical behavior. Since two independent mechanical properties are necessary for full definition of mechanical properties of MEMS materials, their properties can be accurately determined by measuring Young’s modulus and Poisson’s ratio. Young’s modulus (E) is a measure of a material stiffness. It is the slope of the linear part of stress-strain (ε-σ) curve of a material. Poisson’s ratio is a measure of lateral expansion or contraction of a material when subjected to an axial stress within the elastic region. Load-deflection technique enables measuring E together with σ. The concept of this technique is shown in figure 1 using a circular membrane. The load-deflection technique is easy to apply because the membrane is flat without load enabling easy load-deflection relationship measurement. The deflection of the membrane center (d) is measured with the applied pressure (P) across the membrane. Then, the pressure-deflection behavior of a circular membrane (Tsuchiya, 2008) is expressed by
\n\t\t\t\twhere P is the applied pressure, d is the center deflection, \n\t\t\t\t\t
The load-deflection technique for simultaneous E and σ measurement.
Internal stress (σ), the strain generated in thin films on thick substrates, causes the deformation of the microstructure and occasionally destruction of the structure. It has two sources:
\n\t\t\t\tthermal mismatch between a substrate and a thin film – extrinsic stress,
microscopic structural change of a thin film (caused by chemical reactions, ion bombardment, absorption, adsorption etc.) – intrinsic stress.
In case of thin film compression the compressive stress is in question. Compressive stress is expressed as a negative value and it may cause buckling. In case of thin film expansion the tensile stress is in question. Tensile stress is expressed as a positive value and if excessive may lead to fracture of structures. According to Hooke’s law, for isotropic materials under biaxial stress (such as thin films on substrates), internal stress is described by
\n\t\t\t\twhere ε, E and \n\t\t\t\t\t
As a micro fabricated test for strain measurement the beam buckling method is often used. In order to measure ε of thin films the doubly supported beam shown in figure 2 is loaded by the internal stress. The preparation of pattern with incrementally increasing size enables determination of the critical length of the beam which causes buckling.
\n\t\t\t\tDoubly supported beam structure.
The strain deduced from the buckling length of the beam (Tabata, 2006) is given as:
\n\t\t\t\twhere ε, t and lc are the strain, thickness of the thin film and the buckling length, respectively. In this case, the internal stress is assumed to be uniform along the thickness direction. In case of the stress distribution along the thickness direction, variation of ε may cause vertical deflection of the cantilever beam.
\n\t\t\tThe strength of a material determines how much force can be applied to a MEMS device. It needs to be evaluated in order to assure reliability of MEMS devices. Strength depends on the geometry, loading conditions as well as on material properties. As the useful measure for brittle materials, the fracture strength is defined as the normal stress at the beginning of fracture. The flexural strength is a measure of the ultimate strength of a specified beam in bending and it is related to specimen’s size and shape. For inelastic materials, the yield strength is defined as a specific limiting deviation from initial linearity. The tensile strength is defined as a maximum stress the material can withstand before complete failure while the compressive strength is usually related to brittle materials.
\n\t\t\tMEMS devices are often exposed to cyclic or constant stress for a long time during operation. Such operational conditions may induce fatigue. Fatigue may be observed as change in elastic constants and plastic deformation leading to sensitivity changes and offset drift in MEMS devices. It may also be observed as the strength decrease that may lead to fracture and consequentially failure of the device. Fatigue behavior of a MEMS device also depends on its size, surface effects, effect of the environment such as humidity and temperature, resonant frequencies etc. In order to realize highly reliable MEMS device a detailed analysis of the fatigue behavior must be performed using accelerated life test method as well as life prediction method.
\n\t\t\tMinimum features in MEMS are usually of the order of 1µm. Measuring mechanical properties of small MEMS specimens is difficult from the aspects of reliability, repeatability and accuracy of measurements. In order to measure mechanical properties of the MEMS device a specimen must be obtained and mounted. Since the microdevices are produced using deposition and etching processes a specimen must be produced by the same process used in device production. The following step is dimension measurement. The thicknesses of layers are controlled and measured by the manufacturer and lengths are sufficiently large to be measured by an optical microscope with required accuracy. However, the width of the specimen may cause the problem due to its small dimensions as well as imperfect definition of cross section that may cause uncertainty in the area. Therefore, possible measurement techniques include optical or scanning electron microscopy, interferometry, mechanical or optical profilometry. The next step in measuring mechanical properties of MEMS is the application of force/displacement resulting in deformation. This step is followed by force, displacement or strain measurements. Force and displacement measurements are based on tensile and bending tests or on usage of commercially available force and displacement transducers. When strain measurements are in question, it is preferable to measure strain directly on tensile specimens. It enables determination of the entire strain-stress curve from which the properties are obtained. The strain measurement technique known as interferometric strain/displacement gage is usually used apart from variety of other techniques that have not yet been applied to extensive studies of mechanical properties of MEMS. However, in most cases when MEMS materials are in question, direct methods for mechanical properties determination are not suitable. Instead, inverse methods are being used: a model is constructed of the test structure. After the force application and displacement measurements, elastic, inelastic or strength properties can be extracted from the model. Nevertheless, the variations in measured properties are large for both types of testing methods: direct and inverse. The source of variations is not established since there are too many differences among the properties measured by different methods. Obviously, the development of international standards for measuring the mechanical properties of MEMS materials will result in more accurate properties and reliable measurements.
\n\t\t\tWhen tensile testing methods are concerned there are three arrangements that can be used. The first of them is specimen in a supporting frame. The tensile specimen is patterned onto the wafer surface and the gage section is exposed by etching the window in the back of the wafer. The specimen suspended across a rectangular frame enables convenient handling and testing. An example of specimen in a supporting frame is shown in figure 3.
\n\t\t\t\tSchematic of a silicon carbide tensile specimen in a silicon support frame.
The second arrangement used in tensile testing is a specimen fixed at one end. At one end the test specimens fixed to the die while the other is connected to the test system. There is a variety of ways a specimen fixed at one end may be connected to a test system. A free end may be gripped by the electrostatic probe, glued to the force/displacement transducer, connected to the test system by the pin in case of ring shaped grip end, etc. An example of specimen fixed at one end is shown in figure 4.
\n\t\t\t\tSchematic of a tensile specimen fixed to the die at one end.
The third arrangement used in tensile tests of MEMS materials is the freestanding specimen. This arrangement applies to small tensile specimens with submillimeter dimensions. The geometry commonly used in these tests is shown in figure 5. Microspecimens have grip ends that can be fitted into inserts in the grips of the test machine.
\n\t\t\t\tSchematic of nickel free standing microspecimen on a silicon substrate.
Similar to tensile testing methods, bend tests also use three arrangements. The first of them is out-of plane bending. Long, narrow and thin beams of the test material are being patterned on the substrate. The material under the cantilever beam is being etched away leaving the beam hanging freely over the edge. By applying the force as shown in figure 6 and measuring the force vs. deflection at the end or near the end of the beam, Young’s modulus can be extracted.
\n\t\t\t\tShematic of crystal silicon cantilever microbeam that can be used in out-of-plane bending test.
The second arrangement used in bend tests is the beam with fixed ends – so called fixed-fixed beam. The schematic of the most usually used on-chip structure is shown in figure 7. Between the silicon substrate and polysilicon beam with clamped ends a voltage is applied pulling the beam down. The voltage that causes the beam to make contact is a measure of beam’s stiffness.
\n\t\t\t\tThe third arrangement used in bend testing of MEMS materials is in-plane bending (fig. 8). Test structure consisting of cantilever beams subjecting to in-plane bending may be used in fracture strain determination, crack growth and fracture toughness measurements, etc.
\n\t\t\t\tSchematic of a polysilicon fixed-fixed beam on a silicon substrate.
Schematic of polysilicon cantilever beam subjected to in-plane bending.
Resonant structure tests are being used for determination of elastic properties of MEMS devices. Very small test structures used in these tests can be excited by capacitive comb drives which require only electrical contact making this approach suitable for on-chip testing. The most often used resonant structure concepts also include different in-plane resonant structures with a variety of easily modeled geometries as well as test structures based on arrays of cantilever beams fixed at one or both ends excited in different manners. As an illustration, in figure 9 a schematic of a in-plane resonant structure is shown.
\n\t\t\t\tSchematic of the in-plane resonant structure.
Bulge testing is also often called membrane testing. By etching the substrate material a thin membrane of test material is formed. The ideal architecture to achieve a direct tensile testing scheme involves a free standing membrane fixed at both ends (Espinosa, 2003) as shown in figure 10. When load is applied at the center of the membrane (usually using nanoindenter), a uniform stretch on the two halves of the thin membrane is achieved. In this manner the specimen’s structural response is obtained as well as elastic behavior and residual stress state.
\n\t\t\t\tShematic of an Au membrane used in bulge testing.
In indentation tests a miniature and highly sensitive hardness tester (nanoindenter) is being used allowing force and displacement measurements. Penetration depths can be a few nanometers deep and automation permits multiple measurements and thus provides more reliable results. In such a manner Young’s modulus and strength of various thin films can be obtained. As an illustration, a schematic of an indentation test is given in figure 11.
\n\t\t\t\tSchematic of indentation test.
In order to measure forces in specimens the buckling test method can be used and if the specimen under pressure breaks the estimate of fracture strength can be obtained. This test method applied to test structures with different geometries and based on different MEMS materials can be used for determination of the Poisson’s ratio, strain at fracture, residual strain in film, etc.
\n\t\t\t\tAnother test method is the creep test. Creep tests are usually performed in cases when possibility of creep failure exists such as in thermally actuated MEMS devices resulting in a strain vs. time creep curve.
\n\t\t\t\tWhen torsion, one of important modes of deformation in some of MEMS devices, is concerned a few torsion tests have been developed enabling force and deflection measurements.
\n\t\t\t\tFracture tests are of interest when brittle materials are in question. Fracture toughness is being measured using crack formation with a tip radius small relative to the specimen dimensions. Different positions and shapes of cracks are being used formed using different means such as etching, various types of indenters, etc.
\n\t\t\t\tWhen mechanical testing of MEMS materials is in question, standardization of test methods is a challenging task. A step forward in the direction of standardization may be implementation of “round robin” tests that should involve all relevant MEMS researchers in an effort to test common materials used in MEMS at their premises using the method of their choice. First such tests resulted in significant variation of results suggesting that further efforts should be made by involving more scientific resources.
\n\t\t\tPolysilicon is the most frequently used MEMS material. In table 1 polysilicon mechanical properties data is given obtained by three types of tests: bulge, bend and tensile tests. Presented results show that polysilicon has Young’s modulus mostly in the range between 160 and 180 GPa. Fracture strength depends on flaws in the material and performed tests do not necessarily lead to failure of the specimen. For that reason there are fewer entries for fracture strength and obtained results vary.
\n\t\t\tMechanical properties of single-crystal silicon are given in table 2. Presented data is obtained using bending, tensile and indentation tests. The average values for the Young modulus ranged between 160 an 190 GPa.
\n\t\t\tIn table 3 silicon-carbide mechanical properties data is presented. It is a promising MEMS material because of its superior properties (strength, stability, stiffness) and because of the current work on thin-film manufacturing processes few results are available obtained using bulge, indentation and bending tests.
\n\t\t\tSilicon nitride and silicon oxide mechanical properties data is presented in tables 4 and 5, respectively. Silicon nitride is used as an insulating layer in MEMS devices but it also has a potential as a structural material. On the other hand, silicon oxide because of its properties (low stiffness and strength) although included in MEMS devices does not have a potential of becoming a MEMS structural material.
\n\t\t\tThere are few reports regarding the mechanical properties of metal thin films. Table 6 lists measured values of mechanical properties of metal materials commonly used in MEMS devices: gold, copper, aluminum and titanium. Metal films are tested using tensile testing in a free-standing manner. Results for electroplated nickel and nickel-iron MEMS materials are given in table 7. Presented results are obtained using tensile testing methods. Electroplated nickel and nickel-iron MEMS are usually manufactured by LIGA process. The microstructure and electrical properties of electroplated nickel are highly dependent on electroplating conditions while the properties of nickel-iron alloy depend on its composition.
\n\t\t\tMethods | \n\t\t\t\t\t\tYoung’fs Modulus [GPa] | \n\t\t\t\t\t\tFracture Strength [GPa] | \n\t\t\t\t\t
Bulge test | \n\t\t\t\t\t\t160 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Bulge test | \n\t\t\t\t\t\t190-240 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Bulge test | \n\t\t\t\t\t\t151-162 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Bulge test | \n\t\t\t\t\t\t162±4 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Bending test | \n\t\t\t\t\t\t- | \n\t\t\t\t\t\t2.11-2.77 | \n\t\t\t\t\t
Bending test | \n\t\t\t\t\t\t170 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Bending test | \n\t\t\t\t\t\t174±20 | \n\t\t\t\t\t\t2.8±0.5 | \n\t\t\t\t\t
Bending test | \n\t\t\t\t\t\t135±10 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Bending test | \n\t\t\t\t\t\t198 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Bending test | \n\t\t\t\t\t\t- | \n\t\t\t\t\t\t3.2±0.3 | \n\t\t\t\t\t
Bending test | \n\t\t\t\t\t\t- | \n\t\t\t\t\t\t3.4±0.5 | \n\t\t\t\t\t
Tensi le test | \n\t\t\t\t\t\t164-176 | \n\t\t\t\t\t\t2.86-3.37 | \n\t\t\t\t\t
Tensile test | \n\t\t\t\t\t\t- | \n\t\t\t\t\t\t0.57-0.77 | \n\t\t\t\t\t
Tensile test | \n\t\t\t\t\t\t140 | \n\t\t\t\t\t\t0.7 | \n\t\t\t\t\t
Tensile test | \n\t\t\t\t\t\t160-167 | \n\t\t\t\t\t\t1.08-1.25 | \n\t\t\t\t\t
Tensile test | \n\t\t\t\t\t\t169±6 | \n\t\t\t\t\t\t1.20±0.15 | \n\t\t\t\t\t
Tensile test | \n\t\t\t\t\t\t132 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Tensile test | \n\t\t\t\t\t\t140±14 | \n\t\t\t\t\t\t1.3±0.1 | \n\t\t\t\t\t
Tensile test | \n\t\t\t\t\t\t172±7 | \n\t\t\t\t\t\t1.76 | \n\t\t\t\t\t
Tensile test | \n\t\t\t\t\t\t167 | \n\t\t\t\t\t\t2.0-2.7 | \n\t\t\t\t\t
Tensile test | \n\t\t\t\t\t\t163 | \n\t\t\t\t\t\t2.0-2.8 | \n\t\t\t\t\t
Tensile test | \n\t\t\t\t\t\t- | \n\t\t\t\t\t\t1.8-3.7 | \n\t\t\t\t\t
Tensile test | \n\t\t\t\t\t\t166±5 | \n\t\t\t\t\t\t1.0±0.1 | \n\t\t\t\t\t
Tensile test | \n\t\t\t\t\t\t- | \n\t\t\t\t\t\t4.27±0.61 | \n\t\t\t\t\t
Tensile test | \n\t\t\t\t\t\t- | \n\t\t\t\t\t\t2.85±0.40 | \n\t\t\t\t\t
Tensile test | \n\t\t\t\t\t\t- | \n\t\t\t\t\t\t3.23±0.25 | \n\t\t\t\t\t
Tensile test | \n\t\t\t\t\t\t158±8 | \n\t\t\t\t\t\t1.56±0.25 | \n\t\t\t\t\t
Tensile test | \n\t\t\t\t\t\t- | \n\t\t\t\t\t\t2.9±0.5 | \n\t\t\t\t\t
Fixed ends test | \n\t\t\t\t\t\t123 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Fixed ends test | \n\t\t\t\t\t\t171-176 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Fixed ends test | \n\t\t\t\t\t\t149±10 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Fixed ends test | \n\t\t\t\t\t\t178±3 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Polysilicon mechanical properties data (Sharpe, 2001).
Presented results show that these materials have high strength values (especially Ni-Fe) and therefore are suitable for application in actuators.
\n\t\t\tIn table 8 diamond-like carbon mechanical properties data is presented. Diamond-like carbon is a MEMS material with excellent properties such as high stiffness and strength and low coefficient of friction. Presented results are obtained using three types of test methods: bending, buckling and tensile tests.
\n\t\t\tMethods | \n\t\t\t\t\t\tYoung’fs Modulus [GPa] | \n\t\t\t\t\t\tFracture Strength [GPa] | \n\t\t\t\t\t
Bending test | \n\t\t\t\t\t\t177±18 | \n\t\t\t\t\t\t2.0-4.3 | \n\t\t\t\t\t
Bending test | \n\t\t\t\t\t\t163 | \n\t\t\t\t\t\t"/3.4 | \n\t\t\t\t\t
Bending test | \n\t\t\t\t\t\t122±2 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Bending test | \n\t\t\t\t\t\t173±13 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Bending test | \n\t\t\t\t\t\t- | \n\t\t\t\t\t\t0.7-3.0 | \n\t\t\t\t\t
Bending test | \n\t\t\t\t\t\t165±20 | \n\t\t\t\t\t\t2-8 | \n\t\t\t\t\t
Bending test | \n\t\t\t\t\t\t- | \n\t\t\t\t\t\t2-6 | \n\t\t\t\t\t
Bending test | \n\t\t\t\t\t\t169.9 | \n\t\t\t\t\t\t0.5-17 | \n\t\t\t\t\t
Tensile test | \n\t\t\t\t\t\t147 | \n\t\t\t\t\t\t0.26-0.82 | \n\t\t\t\t\t
Tensile test | \n\t\t\t\t\t\t125-180 | \n\t\t\t\t\t\t1.3-2.1 | \n\t\t\t\t\t
Tensile test | \n\t\t\t\t\t\t142±9 | \n\t\t\t\t\t\t1.73 | \n\t\t\t\t\t
Tensile test | \n\t\t\t\t\t\t- | \n\t\t\t\t\t\t0.59±0.02 | \n\t\t\t\t\t
Tensile test | \n\t\t\t\t\t\t169.2±3.5 | \n\t\t\t\t\t\t0.6-1.2 | \n\t\t\t\t\t
Tensile test | \n\t\t\t\t\t\t164.9±4 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Indentation test | \n\t\t\t\t\t\t60-200 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Indentation test | \n\t\t\t\t\t\t168 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Single-crystal silicon mechanical properties data (Sharpe, 2001).
Methods | \n\t\t\t\t\t\tYoung’fs Modulus [GPa] | \n\t\t\t\t\t
Bulge test | \n\t\t\t\t\t\t394 | \n\t\t\t\t\t
Bulge test | \n\t\t\t\t\t\t88±10 - 242±30 | \n\t\t\t\t\t
Bulge test | \n\t\t\t\t\t\t331 | \n\t\t\t\t\t
Indentation test | \n\t\t\t\t\t\t395 | \n\t\t\t\t\t
Bending test | \n\t\t\t\t\t\t470±10 | \n\t\t\t\t\t
Silicon-carbide mechanical properties data (Sharpe, 2001).
Methods | \n\t\t\t\t\t\tYoung’fs Modulus [GPa] | \n\t\t\t\t\t\tFracture Strength [GPa] | \n\t\t\t\t\t
Resonant test | \n\t\t\t\t\t\t130 - 146±20% | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Resonant test | \n\t\t\t\t\t\t192 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Resonant test | \n\t\t\t\t\t\t194.25±1% | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Bulge test | \n\t\t\t\t\t\t230 & 330 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Bulge test | \n\t\t\t\t\t\t110 & 160 | \n\t\t\t\t\t\t0.39-0.42 | \n\t\t\t\t\t
Bulge test | \n\t\t\t\t\t\t222±3 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Indentation test | \n\t\t\t\t\t\t101-251 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Indentation test | \n\t\t\t\t\t\t216±10 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Silicon-nitride mechanical properties data (Sharpe, 2001).
Methods | \n\t\t\t\t\t\tYoung’fs Modulus [GPa] | \n\t\t\t\t\t\tFracture Strength [GPa] | \n\t\t\t\t\t
Indentation test | \n\t\t\t\t\t\t64 | \n\t\t\t\t\t\t"/0.6 | \n\t\t\t\t\t
Bending test | \n\t\t\t\t\t\t83 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Tensi le test | \n\t\t\t\t\t\t- | \n\t\t\t\t\t\t0.6-1.9 | \n\t\t\t\t\t
Silicon-oxide mechanical properties data (Sharpe, 2001).
\n\t\t\t\t\t\t | E bulk [GPa] | \n\t\t\t\t\t\tYoung’fs Modulus [GPa] | \n\t\t\t\t\t\tYield Strength [GPa] | \n\t\t\t\t\t\tUltimate Strength [GPa] | \n\t\t\t\t\t
Gold | \n\t\t\t\t\t\t74 | \n\t\t\t\t\t\t98±4 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Gold | \n\t\t\t\t\t\t74 | \n\t\t\t\t\t\t82 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t\t0.33-0.36 | \n\t\t\t\t\t
Copper | \n\t\t\t\t\t\t117 | \n\t\t\t\t\t\t86-137 | \n\t\t\t\t\t\t0.12-0.24 | \n\t\t\t\t\t\t0.33-0.38 | \n\t\t\t\t\t
Aluminum | \n\t\t\t\t\t\t69 | \n\t\t\t\t\t\t8-38 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t\t0.04-0.31 | \n\t\t\t\t\t
Aluminum | \n\t\t\t\t\t\t69 | \n\t\t\t\t\t\t40 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t\t0.15 | \n\t\t\t\t\t
Titanium | \n\t\t\t\t\t\t110 | \n\t\t\t\t\t\t96±12 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t\t0.95±0.15 | \n\t\t\t\t\t
Metal films mechanical properties data (tensile test) (Sharpe, 2001; Tabata, 2006).
\n\t\t\t\t\t\t | Young’fs Modulus [GPa] | \n\t\t\t\t\t\tYield Strength [GPa] | \n\t\t\t\t\t\tUltimate Strength [GPa] | \n\t\t\t\t\t
Ni | \n\t\t\t\t\t\t202 | \n\t\t\t\t\t\t0.4 | \n\t\t\t\t\t\t0.78 | \n\t\t\t\t\t
Ni | \n\t\t\t\t\t\t176±30 | \n\t\t\t\t\t\t0.32±0.03 | \n\t\t\t\t\t\t0.55 | \n\t\t\t\t\t
Ni | \n\t\t\t\t\t\t131-160 | \n\t\t\t\t\t\t0.28-0.44 | \n\t\t\t\t\t\t0.46-0.76 | \n\t\t\t\t\t
Ni | \n\t\t\t\t\t\t231±12 | \n\t\t\t\t\t\t1.55±0. 0 5 | \n\t\t\t\t\t\t2.47±0.07 | \n\t\t\t\t\t
Ni | \n\t\t\t\t\t\t181±36 | \n\t\t\t\t\t\t0.33±0.03 | \n\t\t\t\t\t\t0.44±0.04 | \n\t\t\t\t\t
Ni | \n\t\t\t\t\t\t158±22 | \n\t\t\t\t\t\t0.32±0.02 | \n\t\t\t\t\t\t0.52±0.02 | \n\t\t\t\t\t
Ni | \n\t\t\t\t\t\t182±22 | \n\t\t\t\t\t\t0.42±0.02 | \n\t\t\t\t\t\t0.60±0.01 | \n\t\t\t\t\t
Ni | \n\t\t\t\t\t\t156±9 | \n\t\t\t\t\t\t0.44±0.03 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Ni | \n\t\t\t\t\t\t160±1 | \n\t\t\t\t\t\t0.28 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Ni | \n\t\t\t\t\t\t194 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Ni-Fe | \n\t\t\t\t\t\t119 | \n\t\t\t\t\t\t0.73 | \n\t\t\t\t\t\t1.62 | \n\t\t\t\t\t
Ni-Fe | \n\t\t\t\t\t\t155 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t\t2.26 | \n\t\t\t\t\t
Ni-Fe | \n\t\t\t\t\t\t- | \n\t\t\t\t\t\t1.83-2.20 | \n\t\t\t\t\t\t2.26-2.49 | \n\t\t\t\t\t
Electroplated nickel and nickel-iron mechanical properties data (tensile test) (Sharpe, 2001; Tabata, 2006).
Methods | \n\t\t\t\t\t\tYoung’fs Modulus [GPa] | \n\t\t\t\t\t\tFracture Strength [GPa] | \n\t\t\t\t\t
Bending test | \n\t\t\t\t\t\t600-1100 | \n\t\t\t\t\t\t0.8-1.8 | \n\t\t\t\t\t
Buckling test | \n\t\t\t\t\t\t94-128 | \n\t\t\t\t\t\t- | \n\t\t\t\t\t
Tensi le test | \n\t\t\t\t\t\t- | \n\t\t\t\t\t\t8.5±1.4 | \n\t\t\t\t\t
Diamond-like carbon mechanical properties data (Sharpe, 2001).
The measurement of MEMS materials mechanical properties is crucial for the design and evaluation of MEMS devices. Even though a lot of research has been carried out to evaluate the repeatability, accuracy and data reliability of various measurement methods for mechanical properties of MEMS materials, the manufacturing and testing technology for materials used in MEMS is not fully developed. In this chapter an overview of basic test methods and mechanical properties of MEMS materials is given along with definitions of mechanical properties of interest. Also, a summary of the mechanical properties of various MEMS materials is given. Variation of obtained results for common materials may be attributed to the lack of international standards on MEMS materials and their properties measurement methods. It must be pointed out that although MEMS is an area of technology of rapidly increasing economic importance with anticipated significant growth, the ability to develop viable MEMS is to a large degree constrained by the lack of international standards on MEMS materials and their properties measurement methods that would establish fundamentals of reliability evaluation, especially on MEMS material properties.
\n\t\tAuthors are grateful for the partial support of the Ministry of Science and Technological Development of Republic of Serbia (contract ТР- 11014).
\n\t\tEpilepsy is defined by recurrent, spontaneous seizures arising from hyperexcitable neurons in the brain. Yet despite a wide array of anti-epileptic drugs and the option of surgery, approximately one-third of children and adults with epilepsy continue to experience drug-resistant seizures [1]. Many of these patients may be candidates for a ketogenic diet, a well-established, non-pharmacologic therapeutic option proven to improve seizure control in epilepsy [2, 3].
The origins of ketogenic diets derive from the ancient practice of fasting [4], widely acknowledged as effective in treating epilepsy since the 5th century BC; indeed, until the 19th century, epilepsy was believed to be a disease of “eating too much” [5]. Depending on a person’s body fat stores, fasting can be maintained for a considerable length of time (the record for a single continuous fast is 382 days) [6]. However, since everyone must eventually eat, fasting is not a feasible long-term solution for seizure control in epilepsy.
In 1921, Wilder addressed this problem by developing a high-fat, low-carbohydrate diet designed to mimic the metabolic profile of fasting [4]. The high-fat, low-carbohydrate nature of the diet elevated blood ketones and lowered blood glucose levels, producing a metabolic profile similar to that of a multi-day fast. Unlike fasting, Wilder’s diet provided adequate long-term nutrient intake, thus preventing malnutrition and promoting healthy long-term growth and development. Since the diet increased hepatic ketogenesis, it became known as a “ketogenic diet.”
In essence, a ketogenic diet is any high-fat, adequate-protein, low-carbohydrate diet that forces the body to burn fats—not carbohydrates—as the primary energy source [7, 8]. During this process, the liver converts fats into ketone bodies, or “ketones” (organic molecules that readily serve as energy substrates for non-hepatic organs, particularly brain, heart, and skeletal muscle) [9]. The three endogenous ketones are acetone, acetoacetate, and beta-hydroxybutyrate (BHB) [7]; BHB is the primary blood ketone. During a sustained ketogenic diet, the blood BHB level is elevated, and lies within the range of 0.5–8 mmol/L, constituting a state of “physiological ketosis” (in contrast to pathological ketoacidosis, which is associated with a blood BHB level of 15–20 mmol/L or higher, and a concomitant lowering of blood pH) [10].
Ketogenic diets appear to improve seizure control through a variety of mechanisms that collectively stabilize neuron synaptic function (Table 1) [7, 8]. It is not known whether the key mediators of improved seizure control are the ketones themselves, or additional metabolic changes induced by the diets [11].
General mechanism | Specific mechanism |
---|---|
Enhanced neuron energetics | Enhanced neuron ATP production |
Stimulated mitochondrial biogenesis | |
Reduced neuron excitability | Hyperpolarized potassium channels |
Altered glutamate to GABA ratio | |
Increased extracellular adenosine | |
Direct antiseizure effects | Ketone-mediated antiseizure effects |
Raised medium-chain fatty acids | |
Reduced glucose metabolism | |
Other mechanisms | Reduced oxidative stress |
Reduced inflammation |
Mechanisms through which ketogenic diets may stabilize synaptic function.
ATP = adenosine triphosphate; GABA = γ-aminobutyric acid.
The most conspicuous metabolic change induced by a ketogenic diet is elevated blood ketone levels [7]. While it is well-documented that ketones enhance neuron energetics, accumulating evidence suggests they may also play direct and indirect roles in reducing neuron excitability, exerting direct antiseizure effects, and decreasing generation of reactive oxygen species and inflammatory mediators [7, 8, 11]. Thus, there are multiple avenues by which ketones may contribute to improved seizure control; they are not just “energy molecules” [11].
Ketones enhance intracellular adenosine triphosphate (ATP) levels and bioenergetic capacity by increasing mitochondrial oxidative phosphorylation [12]. The oxidation of acetoacetate and BHB feeds acetyl-CoA directly into the Krebs cycle through anaplerosis (the replenishing of depleted metabolic cycle intermediates) [7], which increases the turnover of the Krebs cycle, generating additional protons and electrons that are channeled to the electron transport chain where they may be used to enhance ATP production [12].
Ketones may also inhibit neuronal excitability. ATP-dependent potassium channels, which hyperpolarize the cell membrane, are activated by ketones, decreasing spontaneous cell firing rates [13]. Moreover, acetoacetate concentrations well within the range produced by a ketogenic diet inhibit vesicle loading of the excitatory neurotransmitter glutamate, resulting in reduced glutamate release into the synapse and enhanced synthesis of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) [14]. It is thought that the ensuing altered glutamate to GABA ratio reduces neuron excitability.
Studies dating back to the 1930s also support the direct antiseizure effects of ketones [15, 16]. In mice, acetone and acetoacetate raise seizure thresholds, resulting in fewer seizures [15, 16]. Although BHB did not appear to contribute to antiseizure effects in these earlier studies, more recent studies indicate that BHB probably does play a direct antiseizure role, and that its effects may have been previously missed for methodological reasons [11].
Lastly, ketones may influence seizure control by lowering cell oxidative stress and inflammation [11]. BHB inhibits histone deacetylases (enzymes that remove acetyl groups from lysine residues on histones, allowing DNA to wrap tightly and preventing gene expression), resulting in upregulated anti-oxidant genes and reduced oxidative stress in kidney cells [17]. Moreover, BHB inhibits the assembly of the immune sensor nucleotide oligomerization domain (NOD)-like receptor protein 3, a multi-protein complex that controls the release of various inflammatory mediators [18].
Emerging evidence suggests that a number of additional metabolic changes induced by ketogenic diets may also contribute to enhanced neuron energetics, reduced neuron excitability, and direct antiseizure effects, improving seizure control [7, 8].
Ketogenic diets can improve seizure control in patients with mitochondrial disorders [19]. This observation may be partly explained by the action of the medium-chain fatty acid, decanoic acid, on peroxisomal proliferator-activated receptor γ, which stimulates neuronal mitochondrial biogenesis [19]. The increased mitochondrial biomass enhances neuron ATP production capacity and cell energy reserves.
Ketogenic diets may also alter brain levels of the neurotransmitter adenosine. The disruption of adenosine signaling induces seizures; this effect is reversible by a ketogenic diet [20]. This observation suggests that the diet increases extracellular adenosine levels, activating inhibitory adenosine A1 receptors and reducing neuron hyperexcitability [7].
Lastly, ketogenic diets may exert direct antiseizure effects by raising medium-chain fatty acid levels and decreasing glucose metabolism [7, 8]. The medium-chain fatty acid, decanoic acid, blocks seizure-like activity in animals [21]. Moreover, since the antiseizure effects of ketogenic diets can be rapidly reversed by glucose infusions, decreased glucose metabolism is thought to contribute to seizure control. The mechanism for this effect could be partially explained by the observation that ketogenic diets induce a reduction in glycolysis, subsequently repressing the expression of brain-derived neurotrophic factor, a known pro-convulsant [7].
To date, four major, “conventional” ketogenic diets are supported by published evidence in the treatment of children and adults with epilepsy (Table 2) [2, 3]. The primary difference between each diet lies in the ratio of fat to protein plus carbohydrate, described by weight or by calorie intake.
Ketogenic diet | Macronutrient ratio (by weight) | Macronutrient ratio (by calorie intake) |
---|---|---|
CKD | Fat 80% | Fat 90% |
Protein 12% | Protein 6% | |
Carbohydrate 8% | Carbohydrate 4% | |
MCT diet | Fat 60% | Fat 75% |
Protein 16% | Protein 10% | |
Carbohydrate 24% | Carbohydrate 15% | |
MAD | Fat 50% | Fat 65–70% |
Protein 35% | Protein 25–30% | |
Carbohydrate 15% | Carbohydrate 5% | |
LGIT diet | Fat 40% | Fat 60% |
Protein 45% | Protein 30% | |
Carbohydrate 15% | Carbohydrate 10% |
Conventional ketogenic diets supported by published evidence in treating epilepsy.
CKD = classic ketogenic diet; MCT = medium-chain triglyceride; MAD = modified Atkins diet; LGIT = low glycemic index treatment.
Created by Wilder in the 1920s [1], the CKD is the oldest of all ketogenic diet therapies and in its purest form consists of 80% fat by weight (roughly equivalent to 90% fat by caloric intake), translating to a 4:1 ratio of fat to protein plus carbohydrate, although a 3:1 ratio or lower can often be used [2]. In the CKD, the fat source consists predominantly of long-chain fatty acids, obtained from standard foods.
In an effort to make the ketogenic diet more palatable, the MCT diet was introduced in the 1970s [22]. In its original form, the MCT diet is 60% fat by weight (roughly 75% fat by caloric intake), with fat sourced from MCT oils. Since medium-chain fatty acids yield more ketones per kilocalorie compared to long-chain fatty acids, the MCT diet allows for a lower overall fat intake, and a greater intake of protein and carbohydrate, compared to the CKD. A number of patients are prone to gastrointestinal side-effects on this diet, so a modified MCT diet was created in the 1980s, consisting of 30% medium-chain fatty acids plus 30% long-chain fatty acids by weight [23].
In the early 2000s, the MAD was shown to be effective in treating epilepsy [24]. The MAD is approximately 50% fat by weight (65–70% fat by caloric intake), translating to a 1:1 ratio of fat to protein plus carbohydrate, although no set ratio is mandated; it may even approach a 4:1 ratio [2]. The MAD eases up on the protein and carbohydrate restrictions imposed by the CKD and MCT diet, and does not require food weighing.
The LGIT, roughly 40% fat by weight (60% fat by caloric intake), was introduced in the early 2000s as a treatment for epilepsy [25]. The design of the LGIT was based on the hypothesis that stable glucose levels contribute to the seizure control conferred by ketogenic diets. The LGIT allows for relatively liberal levels of protein and carbohydrate intake, emphasizing carbohydrates with glycemic indices less than 50.
Unfortunately, many children throughout the world still lack access to a pediatric epilepsy center containing a specialized ketogenic service with both inpatient and outpatient management options [2]. Such a service should consist of a pediatric neurologist, nurse, dietitian, and ideally case managers, psychologists, social workers, and pharmacists [2, 26].
Ketogenic diets in children are strongly indicated in drug-resistant epilepsy, two disorders of brain metabolism, and several other seizure disorders (Table 3) [2]. There is virtually no age restriction as to when the diet may be commenced; in fact, infants younger than 2 years may be an ideal age group [27].
General disorder | Specific disorder |
---|---|
Drug-resistant epilepsy | 2010 ILAE definition |
Disorders of brain metabolism | GLUT1 DS |
PDHD | |
Specific seizure disorders | Angelman syndrome |
Complex I mitochondrial disorders | |
Doose syndrome | |
Dravet syndrome | |
FIRES | |
Formula-fed | |
Infantile spasms | |
Ohtahara syndrome | |
Super-refractory status epilepticus | |
Tuberous sclerosis complex |
Epilepsy disorders in children for which a ketogenic diet may be strongly indicated.
ILAE = International League Against Epilepsy; GLUT1 DS = glucose transporter type 1 deficiency syndrome; PDHD = pyruvate dehydrogenase complex deficiency; FIRES = febrile infection-related epilepsy syndrome.
In 2010, the International League Against Epilepsy (ILAE) defined drug-resistant epilepsy as the failure of adequate trials of two appropriately chosen, tolerated, and used anti-epileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom [28]. The drugs must have been appropriate for the seizure type, tolerated at therapeutic doses, and given a reasonable period of time to work (at least 6 months) [29] before declaring drug resistance.
When drug-resistant epilepsy is declared, further anti-epileptic drug trials or epilepsy surgery may be helpful [30]. However, even after carefully excluding confounding factors and optimizing the drug approach, subsequent trials have only a slight (about 5%) chance of inducing seizure remission [31]. Surgery should always be considered in children with drug-resistant epilepsy, especially when a lesion concordant to the epilepsy is detected on imaging [30], but many children are not surgical candidates due to a generalized or multifocal epilepsy syndrome, or nonresectable location of ictal onset.
When drug trials and surgery are no longer feasible, a ketogenic diet is indicated [2]. Numerous studies have demonstrated the efficacy and safety of using ketogenic diets to treat drug-resistant epilepsy in children, but until the previous decade there were no randomized controlled trials. Since 2008, four published randomized controlled trials have compared the efficacy of a ketogenic diet with continued medications or a placebo arm in children with drug-resistant epilepsy [32, 33, 34, 35].
The first randomized controlled trial compared the efficacy of a CKD versus no diet intervention in 145 children with drug-resistant epilepsy [32]. After 3 months, 28 children (38%) in the CKD group had a greater than 50% seizure reduction compared to four children (6%) in the control group. One weakness of the study was its unblinded design, with both patients and assessors aware of the group allocations.
The following year, a randomized controlled trial was published in 20 children with drug-resistant Lennox-Gastaut syndrome [33]. All patients were fasted 36 hours and then randomized to receive either a CKD plus a daily solution containing 60 g glucose per day or a solution containing saccharin (an artificial sweetener); the aim of the design was to ensure that both patients and assessors remained blinded to treatment. To the surprise of the investigators, both groups had positive blood BHB levels after 6 days, indicating that the glucose solution did not suppress physiological ketosis. Perhaps as a result of this, the study demonstrated only a borderline, non-statistically significant reduction in seizures in the saccharin arm.
The next randomized controlled trial compared the efficacy of a MAD versus no diet intervention in 102 children with drug-resistant epilepsy [34]. Surgical candidates were not excluded. After 3 months, 52% of children in the MAD group had a greater than 50% seizure reduction compared to 11.5% of those in the control group. A weakness of the study was its unblinded design, with both patients and assessors aware of the group allocations.
The most recent randomized controlled trial compared the efficacy of a ketogenic diet (CKD or MCT diet) versus no diet intervention in 57 children and adolescents with drug-resistant epilepsy [35]. None of the patients were eligible for surgery. After 4 months, 13 children (50%) in the ketogenic diet group had a greater than 50% seizure reduction compared to 4 children (18.2%) in the control group.
Pooling the results from these randomized controlled trials suggests that 40–50% of children experience a greater than 50% seizure reduction after 3–4 months on a ketogenic diet, compared to 10–15% of children receiving no dietary intervention. Given these encouraging results, many epilepsy specialists advocate that ketogenic diets be used earlier in the management of children with drug-resistant epilepsy [2].
Since ketogenic diets induce a shift away from glycolytic energy production towards mitochondrial oxidative phosphorylation, they are the treatment of choice in two childhood disorders of impaired brain glucose metabolism: glucose transporter type 1 deficiency syndrome (GLUT1 DS) and pyruvate dehydrogenase complex deficiency (PDHD) [2]. In both cases, the ketones produced by the diet bypass the metabolic defects, serving as an alternative energy source for the brain.
GLUT1 DS results from impaired glucose transport across the blood-brain barrier due to mutations in the SLC2A1 gene, which encodes the glucose transporter, GLUT1 [36]. Clinically, GLUT1 DS is characterized by cognitive impairment, mixed seizure types, and a complex movement disorder. The vast majority of children with GLUT1 DS achieve seizure freedom with a CKD, which should be introduced as early as possible and continued through to adulthood [36]. The CKD may be difficult to tolerate in older children and adolescents, in which case the MAD is also effective [2]. In GLUT1 DS, ketogenic diets may also enhance the child’s alertness, and they frequently improve the movement disorder [36].
In PDHD, pyruvate is unable to be metabolized into acetyl-CoA, resulting in abnormal mitochondrial metabolism and lactic acidosis [37]. Clinically, PDHD is characterized by seizures, severe encephalopathy, and—usually—death during childhood. The CKD is effective and safe in PDHD, and appears to increase longevity and improve mental development [37]. However, severe forms of PDHD may not be appropriate for the diet if quality of life is not improved [2].
Ketogenic diets should be considered early in the management of children with seizure disorders that consistently demonstrate a 60–70% improvement in seizure control, well above the “usual” 40–50% improvement [2]. These disorders include Angelman syndrome, complex I mitochondrial disorders, Doose syndrome, Dravet syndrome, febrile infection-related epilepsy syndrome (FIRES), formula-fed infants or children, infantile spasms, Ohtahara syndrome, super-refractory status epilepticus, and tuberous sclerosis complex [2].
Once the child is selected for a ketogenic diet, a medical and nutritional evaluation is both strongly advised (Table 4) [2, 26]. In addition to the caregiver (usually a parent), anyone else who will be helping institute the diet should attend.
Evaluation | Steps |
---|---|
Medical | Assess baseline epilepsy state and comorbidities |
Identify psycho-socioeconomic, cultural, and religious factors | |
Review anti-epileptic drugs and medications | |
Provide blood glucose and ketone monitor; show how to use | |
Order investigations | |
Nutritional | Assess baseline physical parameters |
Select most appropriate conventional ketogenic diet | |
Provide supplements | |
Educate caregiver |
Preparing a child (and caregiver) for a ketogenic diet.
A medical evaluation should be performed by a pediatric neurologist experienced in managing ketogenic diets in children, and include an assessment of the child’s epilepsy, comorbidities, psychological and socioeconomic factors, medications, and investigations [2].
First, the pediatric neurologist must assess the child’s baseline epilepsy state and any comorbidities that may complicate a ketogenic diet. Seizure symptomatology and frequency should be documented in sufficient detail so as to later gauge diet efficacy on seizure control. Potential complicating comorbidities include gastrointestinal issues (such as gastroesophageal reflux and constipation), hypercholesterolemia, low weight gain, kidney stones, chronic metabolic acidosis, and cardiomyopathy [2]. Once identified, most comorbidities can be preventatively managed.
Second, it is critical to identify psychological, socioeconomic, cultural, and religious factors that may affect the child’s diet [2]. Challenging behavior traits in the child or caregiver should be addressed early. Since many patients with epilepsy are of lower socioeconomic status, an appraisal of the family environment, including finances, is essential before deciding to proceed; even if deemed adequate, the caregiver must be made aware of the impact of a ketogenic diet on time and resources, including separate meal preparation from the rest of the family and increased costs [26]. It is also necessary to consider the family’s cultural and religious background, which may result in some recipes being more suitable than others [2].
Third, the child’s medications should be reviewed. Generally, blood levels of common anti-epileptic drugs are not significantly altered by a ketogenic diet, therefore dose adjustments are not required. However, it may be worth considering dose reductions in the case of valproate, zonisamide, and topiramate; although these drugs are generally safe alongside a ketogenic diet, there have been rare instances of hepatotoxicity and secondary carnitine deficiency with valproate, as well as chronic metabolic acidosis and a slight increase in kidney stones with zonisamide and topiramate [2]. All medications should be reviewed for carbohydrate content, which may necessitate a switch to lower carbohydrate preparations [26].
Fourth, the child and caregiver should be provided with a means of self-monitoring the diet, which critically provides feedback as to how effectively the child is achieving physiological ketosis [2]. Traditionally, this has been done using urine ketone dipstick testing, but it is now possible to prescribe a blood glucose and ketone monitor in many countries. The former is less expensive and avoids finger pricks, but the latter is easier, more specific, and more accurate [38]. Unless there is a compelling reason to measure urinary ketones, a blood glucose and ketone monitor should be prescribed and the caregiver instructed on its use.
Finally, investigations should be ordered before commencing a ketogenic diet in a child, primarily to rule out contraindications (a ketogenic diet is absolutely contraindicated in disorders of fat metabolism, including carnitine deficiency, carnitine palmitoyltransferase I and II deficiency, any of the short, medium, or long-chain acyl dehydrogenase deficiencies, and porphyria) [2]. Basic laboratory investigations include complete blood count, electrolytes, liver and kidney function tests, fasting lipid profile, calcium, vitamin D, serum acylcarnitine profile, and a urinalysis [2]. Baseline anti-epileptic drug levels can be measured, although few concerns for drug-diet interactions exist. A recent EEG and MRI brain should be obtained to identify potential surgical candidates. Further tests, such as ECG and renal ultrasound, may be ordered as clinically indicated.
A nutritional evaluation should be performed by a dietitian experienced in managing ketogenic diets in children, and include an assessment of baseline physical parameters, selection of the most suitable ketogenic diet, and education of the caregiver on what to expect with the diet.
Baseline weight, body-mass index, and height are routinely measured (in infants, head circumference is also measured) [2]. The child’s recommended calorie and fluid intake should be calculated, as well as the desired fat to protein to carbohydrate ratio. Food aversions and allergies must be clearly documented.
When selecting a conventional ketogenic diet for a child, the most important factor to consider is the family environment, rather than perceived diet efficacy [2]. The CKD is highly effective for seizure control, but restrictive and time-consuming; depending on the family environment, it may be more feasible to implement the MCT diet, MAD, or LGIT diet. Regarding diet efficacy, the CKD appears to be superior to the MAD in infants under 2 years of age, whereas both are equally effective in older children [27]. For the transition to adolescence, the MAD and LGIT diet are less restrictive and more appropriate; the LGIT diet may not provide an adequate level of ketosis to treat GLUT1 DS and PDHD, although it is highly effective in Angelman syndrome [2, 39]. For infants and children on enteral feeds, ketogenic diets can be administered in liquid form, which may be more convenient and efficacious [2].
Given the limited fruit, vegetable, and calcium content in conventional ketogenic diets, supplementation with a carbohydrate-free multivitamin containing minerals, as well as supplementation with calcium and vitamin D, is considered mandatory in children [26]. No particular recommendations exist for supplementing a ketogenic diet with magnesium, selenium, carnitine, laxatives, probiotics, or exogenous ketones [2, 26].
Caregiver education is essential; the caregiver needs to understand exactly what is required of them to implement the diet. A classroom-based format, with several different caregivers present, can be advantageous [26]. The dietitian should demonstrate how to identify sources of fat, protein, and carbohydrate, how to count net carbohydrate (total carbohydrate minus fiber) for those on a MAD, how to identify foods with a low glycemic index for those on an LGIT diet, and how to navigate potential pitfalls [26]. Helpful additional resources should be provided [40, 41] and any expectations addressed.
Once the child and caregiver have been prepared, it is time to implement the diet (Table 5) [2]. The pediatric ketogenic service should take on a strong supportive role, aiding the caregiver as much as possible in troubleshooting problems.
Stage | Steps |
---|---|
Initiation | Decide whether to initiate as inpatient or outpatient |
If inpatient, decide on induction fast and diet introduction | |
If outpatient, provide clear instructions to caregiver | |
Maintenance | Caregiver monitors seizure control and ketone levels |
Review at 1, 3, 6, 9, 12 months, and 6-monthly after | |
Monitor for adverse effects | |
Cessation | Identify when diet should be ceased (if ever) |
If to be ceased, consider switching to another ketogenic diet | |
If to be ceased, decide on rate of diet cessation |
Implementing a ketogenic diet in a child with epilepsy.
Currently, it is recommended that the CKD be initiated with the child in hospital [2]. The advantages of an inpatient admission include the ability to closely observe the child, medically intervene if necessary, and provide more time to educate the caregiver on how to maintain the diet upon returning home.
Traditionally, a 12–24 hours fast has been used to commence the diet in an inpatient setting [2]. Fasting may lead to a quicker onset of seizure reduction, which may be useful in refractory status epilepticus [2]. However, induction fasts do not improve ketosis or seizure control at 3 months, and fasted children experience weight loss, hypoglycemia, and acidosis more frequently, which may increase the length of hospital stay [42]. Thus, although an induction fast should be considered, most pediatric ketogenic services no longer routinely fast children, and none recommend fasting infants under 2 years of age [2].
Regardless of whether an induction fast is utilized, several approaches may be used to introduce the CKD in hospital [2]. One approach involves starting the diet at one-third or one-half of the final calorie level, increasing the calories by one-third or one-half over several days until full calorie intake is achieved, keeping the fat to protein to carbohydrate ratio constant. Another approach is to start with full calorie intake, but increase the ratio of fat to protein plus carbohydrate daily, from 1:1 to 2:1 to 3:1 to 4:1, allowing the child to gradually adapt to the increasing fat intake. Yet another approach is to simply commence the CKD at full calories and a 4:1 ratio on the first day, which does not appear to prolong hospital stay, increase adverse effects, or decrease diet efficacy at 3 months.
In older children, the CKD may be initiated as an outpatient, the advantages of which include reduced family stress and fewer hospital-associated costs [2]. Most pediatric ketogenic services also routinely initiate the less-restrictive MAD and LGIT diet in the outpatient setting. If a graded introduction is required at home, clear instructions must be given to the caregiver on how to do so.
Once initiated, ketogenic diets tend to work rapidly and effectively, with 75% of children responding within 14 days [43]. Complete seizure freedom often occurs within several months of initiation, although it may take up to 18 months [44]. The caregiver should monitor the child’s ketone levels (ideally, the blood BHB level) daily for the first several weeks, then two or three times a week once readings consistently show the child to be in physiological ketosis. Most pediatric ketogenic services recommend a blood BHB level of 4–6 mmol/L, although this is not based on clinical evidence [3]. If seizure control or ketone levels are not responding as expected, a 3-day food diary may be useful to discover potential oversights in diet implementation.
The pediatric neurologist and dietitian should be in frequent phone or email contact with the caregiver during the initial weeks of the diet, with additional follow-up visits occurring at 1, 3, 6, 9, and 12 months, and every 6 months thereafter [2]. The pediatric neurologist should document the child’s seizure response, and regardless of any improvement, resist altering their anti-epileptic drugs unless necessary; alterations may make it difficult to gauge diet efficacy on seizure control. Recommended follow-up tests include complete blood count, electrolytes, liver and kidney function tests, fasting lipid profile, calcium, and vitamin D [2]. Since ketogenic diets and anti-epileptic drugs may predispose a child to osteopenia, some pediatric ketogenic services perform a bone density scan after 2 years on the diet [2]. The dietitian should monitor the child’s physical parameters and nutritional intake at every visit. Ketogenic diets have a diuretic effect and fluid content in the food may be lessened, therefore fluid hydration must be monitored, and increased if necessary [26].
Both the caregiver and the pediatric ketogenic service must monitor the child for adverse effects. Gastrointestinal symptoms such as nausea, vomiting, abdominal pain, and constipation appear in up to 50% of children on the CKD, but are easily remedied by increasing fluid, salt, and fiber intake [2]. Hyperlipidemia is common, with raised triglyceride and low-density lipoprotein (LDL) levels seen in up to 60% of children on the CKD, but the increase is usually transient and normalizes within 1 year; if desired, the LDL can be lowered by altering the types of fats ingested (for example, by increasing olive oil and decreasing saturated fats) [2]. Moreover, ketogenic diets may slightly inhibit a child’s growth; adjustments in calorie intake may compensate. Kidney stones may occur in 3–7% of children on the CKD, but can be prevented with oral citrates [2]. Ultimately, such common adverse effects are rarely sufficient reasons to discontinue the CKD, but rarer adverse effects such as cardiomyopathy, prolonged QT interval, and pancreatitis may provide sufficient reason to do so.
Upon ceasing a ketogenic diet, the long-term benefits on seizure control often outlast the diet itself. In children who become seizure-free on a ketogenic diet, 80% will remain so after diet cessation [45], an effect that can persist for many years.
The child’s ketogenic diet should be maintained for at least 3 months before passing judgment on its efficacy in seizure control [2]. The exception to this rule is if the seizures worsen for longer than 1–2 weeks after commencing the diet, or if a serious adverse effect occurs—in either case, it may be wise to discontinue the diet sooner.
If a child experiences the “usual” greater than 50% seizure reduction, the ketogenic diet is usually discontinued after 2 years [2]. In new-onset infantile spasms, the diet can be ceased at 6 months [46]. In drug-resistant epilepsy in which seizure control is virtually complete (over 90% seizure reduction) and GLUT1 DS, the diet can be carried into adulthood [2]. Older children may start to see their diet as overly restrictive; if it effectively controls the seizures, it may be switched over to another type of ketogenic diet (for example, from a CKD or MCT diet to a MAD or LGIT diet).
A child’s ketogenic diet should be ceased gradually (over several months) [2]. In the case of the CKD, the ratio can be reduced by decreasing the ratio of fat to protein plus carbohydrate monthly, from 4:1 to 3:1 to 2:1 to 1:1, allowing the child to gradually adapt to the decreasing fat intake, followed by the reintroduction of regular foods. However, it is usually still possible to cease the diet more rapidly (over several weeks) without negative consequences, although some children may experience a higher risk of increased seizures during the tapering-down period. If medically necessary, ketogenic diets can be stopped abruptly; this is best done in hospital.
Few epilepsy centers in the world offer a dedicated adult ketogenic service [3]. Such a service should consist of a neurologist, nurse, dietitian, and ideally a psychologist and social worker [3, 47].
Ketogenic diets in adults are indicated in drug-resistant epilepsy and certain seizure disorders (Table 6); they may be used in adults of all ages [47].
General disorder | Specific disorder |
---|---|
Drug-resistant epilepsy | 2010 ILAE definition |
Disorders of brain metabolism | GLUT1 DS |
PDHD | |
Specific seizure disorders | JME |
Lennox-Gastaut syndrome | |
Rett syndrome |
Epilepsy disorders in adults for which a ketogenic diet may be indicated; this list is not comprehensive.
ILAE = International League Against Epilepsy; GLUT1 DS = GLUT1 deficiency syndrome; PDHD = pyruvate dehydrogenase complex deficiency; JME = juvenile myoclonic epilepsy.
In 2010, the ILAE defined drug-resistant epilepsy as the failure of adequate trials of two appropriately chosen, tolerated, and used anti-epileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom [28]. Since adults may suffer from drug-resistant epilepsy for decades, many adult patients have already failed multiple trials of anti-epileptic drugs over their lifetime.
Further anti-epileptic drug trials and epilepsy surgery may be feasible options in adults with drug-resistant epilepsy [30]. However, subsequent drug trials confer only a slight (about 5%) chance of inducing seizure remission [31]. Surgery should always be considered, but some eligible adults may not be ready to pursue surgery [48], and many others will not be eligible due to a generalized or multifocal epilepsy syndrome, or nonresectable lesion of ictal onset.
When drug trials and surgery are not feasible, a ketogenic diet may be indicated [48]. Many single-arm studies have demonstrated the efficacy and safety of ketogenic diets in treating drug-resistant epilepsy in adults, but to date there are no randomized controlled trials of a ketogenic diet in adults with drug-resistant epilepsy.
Surprisingly, a 1930 study remains the largest retrospective case series to examine a ketogenic diet in adults with epilepsy [49]. In this study, 100 adolescents and adults with epilepsy were treated with a CKD. After 1–46 months, 56% of patients had a greater than 50% seizure reduction.
In 2014, a review of all subsequently published ketogenic diet studies in adults with drug-resistant epilepsy was published [50]. Five studies examined the use of a CKD to treat a combined total of 47 adults with drug-resistant epilepsy. After 3–26 months, 15 patients (32%) had a greater than 50% seizure reduction, with 24 patients (51%) stopping the diet before study completion. Another five studies examined the use of a MAD to treat a combined total of 85 adults with drug-resistant epilepsy. After 3–12 months, 24 patients (28%) had a greater than 50% seizure reduction, with 36 patients (42%) stopping the diet before completion. For both diets, most patients withdrew due to culinary and social restrictions.
In 2016, the largest observational study of a ketogenic diet in adults with drug-resistant epilepsy was published, in which 106 patients were treated with a MAD [48]. After 3 months, 38 patients (36%) had a greater than 50% seizure reduction, with 47 patients (44%) not completing the study, largely due to diet restrictiveness.
Pooling the results from these single-arm studies suggests that 30–40% of adults with drug-resistant epilepsy experience a greater than 50% seizure reduction after 3 or more months on a ketogenic diet. While these results are encouraging, they emanate from single-arm studies; moreover, 40–50% of adults stopped their diet before study completion. Clearly, randomized controlled trials involving less restrictive ketogenic diets are needed in adults with drug-resistant epilepsy.
Ketogenic diets remain standard treatments for disorders of impaired brain glucose metabolism in adults [47]. In GLUT1 DS, ketogenic diets have been shown to confer seizure freedom in up to 90% of patients, including adults [47]. The prognosis in more severe forms of PDHD may be poor, but less severely affected individuals may benefit from a ketogenic diet as they transition to adulthood.
In addition to GLUT1 DS and PDHD, ketogenic diet therapy may be warranted in several seizure disorders often seen in adults, including juvenile myoclonic epilepsy (JME), Lennox-Gastaut syndrome, and Rett syndrome [48]. JME is particularly common, representing 5–10% of all epilepsy cases, and typically manifests in adolescence or early adulthood with a combination of myoclonic jerks or seizures, absence seizures, and generalized tonic-clonic seizures. In two separate case series, 60–70% of adolescents and adults with JME experienced a 50% seizure reduction after 3 months of MAD therapy [51, 52].
Once the adult has been selected for the diet, a medical and nutritional evaluation is advised (Table 7) [3, 47]. If possible, a cohabiting partner (spouse or family member) should accompany the adult to the evaluations, and ideally participate in the diet alongside them.
Evaluation | Steps |
---|---|
Medical | Assess baseline epilepsy state and comorbidities |
Identify psycho-socioeconomic, cultural, and religious factors | |
Elucidate level of commitment | |
Review anti-epileptic drugs and medications | |
Provide blood glucose and ketone monitor; show how to use | |
Order investigations | |
Nutritional | Assess baseline physical parameters |
Select most appropriate conventional ketogenic diet | |
If none appropriate, offer a non-conventional ketogenic diet | |
Provide list of foods for social settings | |
Provide supplements | |
Educate patient |
Preparing an adult (and partner) for a ketogenic diet.
A brief medical evaluation should be performed by a neurologist with experience managing ketogenic diets in adults, and should include a history of the epilepsy, comorbidities, psychological and socioeconomic factors, level of commitment to the diet, medications, and investigations [47].
First, the neurologist must ascertain the adult’s baseline epilepsy state and any comorbidities that may complicate their ketogenic diet. The symptomatology and frequency of the various types of seizures should be documented in sufficient detail so as to later gauge diet efficacy on seizure control. Potentially complicating comorbidities include hypercholesterolemia, underweight body-mass index, kidney stones, osteopenia or osteoporosis, gastrointestinal issues (such as gastroesophageal reflux and constipation), cardiomyopathy, and diabetes [3]. Adults with type 1 diabetes can safely pursue a ketogenic diet, but must be closely monitored as their insulin requirements often decline, putting them at risk of hypoglycemia if they do not adjust their insulin doses accordingly [53]. Adults with type 2 diabetes may also start a ketogenic diet [3]; in fact, such adults may be ideal candidates.
Second, it is critical to identify psychological, socioeconomic, cultural, and religious factors with the potential to disrupt the adult’s ketogenic diet [3]. Diet adherence in adults may be endangered by any number of factors, including personality traits, alcohol habits, income, cultural influences, and religious preferences; each must be realistically appraised before the adult and ketogenic service commit to the diet.
Third, the adult’s level of commitment to ketogenic diet therapy must be elucidated. Diet modification often involves a major change in lifestyle, therefore anything less than a full commitment is likely to fail. If the adult holds any reservations about commencing the diet, these should be explored; if unsolvable, the adult may not yet be ready for the diet. The neurologist should counsel the adult on how to deal with inevitable “mixed messages” regarding the purported negative aspects of high-fat diets from friends, family, and even other medical professionals. Lastly, it can be helpful to emphasize the additional positive aspects of a ketogenic diet, such as beneficial effects on cognition, energy, and mood [47].
Fourth, the adult’s medications should be reviewed. In general, anti-epileptic drug blood levels are not altered by a ketogenic diet, therefore dose adjustments are not usually required. However, for the same reasons as in children, exceptions might be made in the case of valproate, zonisamide, or topiramate [2]. All medications should be reviewed for carbohydrate content, which may necessitate a switch to lower carbohydrate preparations [47].
Fifth, the adult should be provided with a means of self-monitoring their diet, which critically provides feedback as to how effectively they are achieving physiological ketosis. In adults, it is best to prescribe a blood glucose and ketone monitor given that this method is easier, more specific, and more accurate than urine dipstick testing [38]. The adult should be shown how to use the monitor.
Finally, investigations should be ordered to rule out contraindications to a ketogenic diet (as a rule, it is not necessary to screen for disorders of fat metabolism in adults, unless the history suggests otherwise) [47]. Laboratory investigations include complete blood count, electrolytes, liver and kidney function tests, fasting lipid profile, calcium, vitamin D, and a urinalysis [3]. Given that the effects of a ketogenic diet on pregnancy are not known [3], pregnancy testing may be indicated in women of childbearing age. Baseline anti-epileptic drug levels can be measured, although few concerns for drug-diet interactions exist. A recent EEG and MRI brain should be obtained to identify potential surgical candidates. Given that ketogenic diets and anti-epileptic drugs may predispose adults to osteopenia, a baseline bone density scan may be wise. Further tests, such as ECG and renal ultrasound, are ordered as clinically indicated.
A nutritional evaluation should be performed by a dietitian experienced in managing ketogenic diets in adults, and ought to include an assessment of baseline physical status, a decision as to which is the most appropriate ketogenic diet option for that adult, and education about their chosen ketogenic diet.
Baseline weight and body-mass index should be measured and recommended calorie and fluid intake calculated, including the desired ratio of fat to protein to carbohydrate [48]. Food aversions and allergies must be clearly documented.
When selecting which conventional ketogenic diet to use, the most important factors to consider in adults are culinary and social restrictions [48, 50]. Since the CKD is the most restrictive of the four, it is rarely a viable long-term option in adults (unless given as a formula). The MCT diet is slightly less restrictive, but still not viable in most adults due to the copious quantities of MCT oil and resulting gastrointestinal side-effects. The MAD and LGIT are less restrictive conventional options in adults, but both are still associated with considerable dropout rates [54]. Thus, although conventional ketogenic diets should be offered, the adult may not be motivated to pursue any of them; this will negatively impact diet implementation.
If conventional ketogenic diets do not appeal to the adult, a fifth option, that of a non-conventional ketogenic diet, can be considered. Such a diet might consist of dietitian-verified recipes obtained from trusted ketogenic diet books and websites, a major advantage of which is that it can be specifically tailored towards the adult’s food preferences, reducing the perception that their diet is restrictive. It is now possible to prepare a variety of ketogenic diets, including vegetarian and culturally-tailored ketogenic diets (theoretically, as long as a ketogenic diet sustains physiological ketosis, it is “ketogenic”). Given that each conventional ketogenic diet is decades old (nearly a century old in the case of the CKD), a newer, less restrictive, patient-tailored ketogenic diet is appealing to many adults, although it must be emphasized that evidence for such a diet in epilepsy may be lacking.
Since many adults with epilepsy are of lower socioeconomic status, the dietitian must strive to minimize any socioeconomic impediments that may disrupt their ketogenic diet. Social activities are to be encouraged, but they can also jeopardize the diet; it is extremely helpful if the dietitian provides a list of appropriate food options relevant to most restaurants and social gatherings that will inform the adult as to what they can and cannot eat, so as not to disrupt the diet. For meals made at home, the dietitian should recommend foods that are both within the adult’s budget range as well as readily available at their local food markets.
Given the limited fruit, vegetable, and calcium content in many ketogenic diets, adults should be commenced on a carbohydrate-free multivitamin [3, 47]. Some ketogenic services also supplement adults with calcium, vitamin D, and magnesium [3, 47].
Lastly, education is essential; the adult needs to understand exactly what is required of them to implement their diet. A classroom-based format, with multiple adult patients present, can be advantageous [26]. The dietitian should demonstrate how to identify sources of fat, protein, and carbohydrate, how to count net carbohydrate (total carbohydrate minus fiber) for those on a MAD or non-conventional ketogenic diet, how to identify foods with a low glycemic index for those on an LGIT diet, and how to navigate potential pitfalls [26]. Helpful additional resources should be provided [55] and any expectations addressed.
Once the adult has been prepared, their chosen diet can be implemented (Table 8) [47]. The ketogenic service should provide as much support as the adult needs, but also encourage them to develop a sense of “ownership” over their diet, thus conferring a feeling of empowerment over their epilepsy.
Stage | Steps |
---|---|
Initiation | Decide whether to initiate as inpatient or outpatient |
If inpatient, decide on induction fast and diet introduction | |
If outpatient, provide clear instructions to caregiver | |
Maintenance | Adult self-monitors seizure control and ketone levels |
Review at 3 and 6 months, and 6-monthly after | |
Monitor for adverse effects | |
Document beneficial effects | |
Cessation | Identify when diet should be ceased (if ever) |
If to be ceased, consider switching to another ketogenic diet | |
If to be ceased, decide on rate of diet cessation | |
If relevant, consider diet cessation and driving |
Implementing a ketogenic diet in an adult with epilepsy.
In younger and disabled adults, it may be more appropriate to initiate a ketogenic diet as an inpatient [48]. The advantages of an admission include the ability to observe the patient and medically intervene if needed, and provide more time to educate the caregiver on how to maintain the diet upon returning home. In general, fasting is not employed in adults, although an induction fast might be useful if a quicker response is required (for example, if the adult is having multiple daily seizures, an induction fast might lessen the interference of the epilepsy on the initiation of the diet) [48]. The same graded approach used to introduce the diet in children may also be used in adults [48].
In most cases, adults with epilepsy can initiate their ketogenic diet as an outpatient, especially if they have selected the MAD, LGIT diet, or a non-conventional ketogenic diet. In most adults, it is not necessary to employ a graded approach when initiating a ketogenic diet at home, but if required then clear instructions should be provided on how to do so.
Ketogenic diets often work rapidly, within days [43]. The adult should regularly monitor their blood BHB level daily for the first several weeks, then two or three times a week once readings indicate that constant physiological ketosis has been achieved. There are no firm recommendations regarding optimal blood BHB levels in adults [3], although aiming for at least 2 mmol/L at all times seems reasonable. If seizure control or ketone levels are not responding as expected, a 3-day food diary may be useful to discover potential oversights in diet implementation.
The neurologist or dietitian should be in regular phone or email contact during the initial weeks of the diet, with multidisciplinary follow-up visits at 3 and 6 months, and every 6 months thereafter [3]. The neurologist should document the adult’s seizure response to the diet; regardless of any improvement, anti-epileptic drugs should not be altered unless necessary, as alterations may make it difficult to gauge diet efficacy on seizure control. Recommended follow-up tests include complete blood count, electrolytes, liver and kidney function tests, fasting lipid profile, calcium, and vitamin D [47]. If osteopenia is a concern, a bone density scan may be warranted every 5 years or less [47], and bone protection therapy prescribed as needed. The dietitian should monitor weight, nutritional intake, and fluid hydration at every visit, and alter each as required.
Adverse effects may occur in adults on a ketogenic diet, but are generally transient, and rarely serious enough to necessitate stopping the diet [47]. The two most common adverse effects in adults are hyperlipidemia and weight loss [48]. Raised LDL levels are seen in least one-quarter of adults with epilepsy [48]. However, triglyceride levels often decline, and HDL levels usually increase [47]. Moreover, among healthy adults following a low-carbohydrate diet, the LDL increase is due to increased LDL particle size rather than particle number, which may be associated with a lower risk of atherosclerosis [56]. Furthermore, LDL and total cholesterol levels typically normalize within a year of commencing the diet [57], and return to baseline within 3 months of stopping it [50]. Weight loss is also common on a ketogenic diet, seen in at least one-fifth of adult with epilepsy [48], but since many such adults are overweight or obese, this adverse effect is often desired and beneficial [47]. Other adverse effects, such as kidney stones and osteopenia or osteoporosis, are rare in adults [47].
Benefits other than seizure control may also occur with a ketogenic diet, including improved arousal, alertness, concentration, energy, and mood [3, 47]. Moreover, adults on a ketogenic diet often report increased quality of life scores [58]. Given that many adults with epilepsy suffer from impaired quality of life, these additional benefits may be significant and should be documented.
Unlike children, the long-term benefits on seizure control in adults with epilepsy may not outlast dietary therapy [59]. Further studies are needed to determine if this is the case for all adults.
It is customary to maintain a ketogenic diet for at least 3 months before passing judgment on its efficacy in seizure control [3]. The exception to this rule is if the seizures worsen for longer than 1–2 weeks after commencing the diet, or if a serious adverse effect occurs—in either case, it may be wise to discontinue the diet sooner.
If the adult experiences a greater than 50% seizure reduction and no serious adverse effects, their ketogenic diet can be maintained indefinitely [3]. If the adult starts to perceive their diet as overly restrictive, yet it remains effective at controlling seizures, it can be switched over to another type of ketogenic diet.
Most ketogenic diets in adults are ceased slowly, over weeks or months on an individual basis [3], although many can be ceased abruptly without negative consequences. The sole exception may be the CKD, which can be ceased gradually by decreasing the ratio of fat to protein plus carbohydrate weekly or monthly, from 4:1 to 3:1 to 2:1 to 1:1, followed by the reintroduction of regular foods.
An important consideration during diet cessation is the effect on driving restrictions. If a ketogenic diet has conferred complete seizure freedom for a long enough period of time such that the adult has returned to driving, stopping the diet applies the same driving restrictions as when anti-epileptic drugs are altered or modified [3].
Historically, ketogenic diets have been utilized as “end of the line” therapeutic options in children and adults with epilepsy. However, given recent advances in the possible mechanisms through which these diets improve seizure control and the growing evidence base supporting their use in epilepsy, this is changing. Significant challenges to the more widespread use of ketogenic diets in children and adults with epilepsy remain, most conspicuously a lack of access to ketogenic services in many regions of the world. Moreover, the culinary and social restrictions associated with conventional ketogenic diets are barriers to their use in adults. If these issues can be addressed, there may come a day when ketogenic diet therapies are utilized more widely, as first-line options alongside drugs and surgery, in the management of children and adults with epilepsy.
The author is grateful for the support of Waikato Hospital, Hamilton, New Zealand.
The author declares no conflict of interest.
Edited by Jan Oxholm Gordeladze, ISBN 978-953-51-3020-8, Print ISBN 978-953-51-3019-2, 336 pages,
\nPublisher: IntechOpen
\nChapters published March 22, 2017 under CC BY 3.0 license
\nDOI: 10.5772/61430
\nEdited Volume
This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\\n\\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\\n\\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\\n\\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\\n\\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\\n\\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\\n\\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\\n\\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\\n\\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\\n\\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\\n\\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\\n\\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
\\n"}]'},components:[{type:"htmlEditorComponent",content:'This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\n\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\n\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\n\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\n\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\n\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\n\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\n\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\n\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\n\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\n\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\n\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
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Marquis, Éric Guillaume and Carine Chivas-Joly",authors:[{id:"44307",title:"Dr",name:"Damien",middleName:"Michel",surname:"Marquis",slug:"damien-marquis",fullName:"Damien Marquis"},{id:"44317",title:"Prof.",name:"Carine",middleName:null,surname:"Chivas-Joly",slug:"carine-chivas-joly",fullName:"Carine Chivas-Joly"}]},{id:"52860",doi:"10.5772/65937",title:"Cerium Oxide Nanostructures and their Applications",slug:"cerium-oxide-nanostructures-and-their-applications",totalDownloads:5365,totalCrossrefCites:23,totalDimensionsCites:55,abstract:"Due to excellent physical and chemical properties, cerium oxide (ceria, CeO2) has attracted much attention in recent years. This chapter aimed at providing some basic and fundamental properties of ceria, the importance of oxygen vacancies in this material, nano‐size effects and various synthesis strategies to form diverse structural morphologies. Finally, some key applications of ceria‐based nanostructures are reviewed. We conclude this chapter by expressing personal perspective on the probable challenges and developments of the controllable synthesis of CeO2 nanomaterials for various applications.",book:{id:"5510",slug:"functionalized-nanomaterials",title:"Functionalized Nanomaterials",fullTitle:"Functionalized Nanomaterials"},signatures:"Adnan Younis, Dewei Chu and Sean Li",authors:[{id:"191574",title:"Dr.",name:"Adnan",middleName:null,surname:"Younis",slug:"adnan-younis",fullName:"Adnan Younis"}]}],mostDownloadedChaptersLast30Days:[{id:"38951",title:"Carbon Nanotube Transparent Electrode",slug:"carbon-nanotube-transparent-electrode",totalDownloads:3985,totalCrossrefCites:3,totalDimensionsCites:5,abstract:null,book:{id:"3077",slug:"syntheses-and-applications-of-carbon-nanotubes-and-their-composites",title:"Syntheses and Applications of Carbon Nanotubes and Their Composites",fullTitle:"Syntheses and Applications of Carbon Nanotubes and Their Composites"},signatures:"Jing Sun and Ranran Wang",authors:[{id:"153508",title:"Prof.",name:"Jing",middleName:null,surname:"Sun",slug:"jing-sun",fullName:"Jing Sun"},{id:"153596",title:"Ms.",name:"Ranran",middleName:null,surname:"Wang",slug:"ranran-wang",fullName:"Ranran Wang"}]},{id:"49413",title:"Electrodeposition of Nanostructure Materials",slug:"electrodeposition-of-nanostructure-materials",totalDownloads:3733,totalCrossrefCites:1,totalDimensionsCites:7,abstract:"We are conducting a multi-disciplinary research work that involves development of nanostructured thin films of semiconductors for different applications. Nanotechnology is widely considered to constitute the basis of the next technological revolution, following on from the first Industrial Revolution, which began around 1750 with the introduction of the steam engine and steelmaking. Nanotechnology is defined as the design, characterization, production, and application of materials, devices and systems by controlling shape and size of the nanoscale. The nanoscale itself is at present considered to cover the range from 1 to 100 nm. All samples prepared in thin film forms and the characterization revealed their nanostructure. The major exploitation of thin films has been in microelectronics, there are numerous and growing applications in communications, optical electronics, coatings of all kinds, and in energy generation. A great many sophisticated analytical instruments and techniques, largely developed to characterize thin films, have already become indispensable in virtually every scientific endeavor irrespective of discipline. Among all these techniques, electrodeposition is the most suitable technique for nanostructured thin films from aqueous solution served as samples under investigation. The electrodeposition of metallic layers from aqueous solution is based on the discharge of metal ions present in the electrolyte at a cathodic surface (the substrate or component.) The metal ions accept an electron from the electrically conducting material at the solid- electrolyte interface and then deposit as metal atoms onto the surface. The electrons necessary for this to occur are either supplied from an externally applied potential source or are surrendered by a reducing agent present in solution (electroless reduction). The metal ions themselves derive either from metal salts added to solution, or by the anodic dissolution of the so-called sacrificial anodes, made of the same metal that is to be deposited at the cathode.",book:{id:"4718",slug:"electroplating-of-nanostructures",title:"Electroplating of Nanostructures",fullTitle:"Electroplating of Nanostructures"},signatures:"Souad A. M. Al-Bat’hi",authors:[{id:"174793",title:"Dr.",name:"Mohamad",middleName:null,surname:"Souad",slug:"mohamad-souad",fullName:"Mohamad Souad"}]},{id:"54226",title:"Localized Surface Plasmon Resonance for Optical Fiber-Sensing Applications",slug:"localized-surface-plasmon-resonance-for-optical-fiber-sensing-applications",totalDownloads:2265,totalCrossrefCites:2,totalDimensionsCites:5,abstract:"It is well known that optical fiber sensors have attracted the attention of scientific community due to its intrinsic advantages, such as lightweight, small size, portability, remote sensing, immunity to electromagnetic interferences and the possibility of multiplexing several signals. This field has shown a dramatic growth thanks to the creation of sensitive thin films onto diverse optical fiber configurations. In this sense, a wide range of optical fiber devices have been successfully fabricated for monitoring biological, chemical, medical or physical parameters. In addition, the use of nanoparticles into the sensitive thin films has resulted in an enhancement in the response time, robustness or sensitivity in the optical devices, which is associated to the inherent properties of nanoparticles (high surface area ratio or porosity). Among all of them, the metallic nanoparticles are of great interest for sensing applications due to the presence of strong absorption bands in the visible and near-infrared regions, due to their localized surface plasmon resonances (LSPR). These optical resonances are due to the coupling of certain modes of the incident light to the collective oscillation of the conduction electrons of the metallic nanoparticles. The LSPR extinction bands are very useful for sensing applications as far as they can be affected by refractive index variations of the surrounding medium of the nanoparticles, and therefore, it is possible to create optical sensors with outstanding properties such as high sensitivity and optical self-reference. In this chapter, the attractive optical properties of metal nanostructures and their implementation into different optical fiber configuration for sensing or biosensing applications will be studied.",book:{id:"5721",slug:"nanoplasmonics-fundamentals-and-applications",title:"Nanoplasmonics",fullTitle:"Nanoplasmonics - Fundamentals and Applications"},signatures:"Pedro J. Rivero, Javier Goicoechea and Francisco J. Arregui",authors:[{id:"69816",title:"Dr.",name:"Javier",middleName:null,surname:"Goicoechea",slug:"javier-goicoechea",fullName:"Javier Goicoechea"},{id:"188796",title:"Dr.",name:"Pedro J.",middleName:null,surname:"Rivero",slug:"pedro-j.-rivero",fullName:"Pedro J. Rivero"},{id:"197277",title:"Dr.",name:"Francisco",middleName:null,surname:"Arregui",slug:"francisco-arregui",fullName:"Francisco Arregui"}]},{id:"25297",title:"Nanofabrication of Metal Oxide Patterns Using Self-Assembled Monolayers",slug:"nanofabrication-of-metal-oxide-patterns-using-self-assembled-monolayers",totalDownloads:3443,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"860",slug:"nanofabrication",title:"Nanofabrication",fullTitle:"Nanofabrication"},signatures:"Yoshitake Masuda",authors:[{id:"12385",title:"Dr.",name:"Yoshitake",middleName:null,surname:"Masuda",slug:"yoshitake-masuda",fullName:"Yoshitake Masuda"}]},{id:"77225",title:"Piezoelectricity and Its Applications",slug:"piezoelectricity-and-its-applications",totalDownloads:510,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The piezoelectric effect is extensively encountered in nature and many synthetic materials. Piezoelectric materials are capable of transforming mechanical strain and vibration energy into electrical energy. This property allows opportunities for implementing renewable and sustainable energy through power harvesting and self-sustained smart sensing in buildings. As the most common construction material, plain cement paste lacks satisfactory piezoelectricity and is not efficient at harvesting the electrical energy from the ambient vibrations of a building system. In recent years, many techniques have been proposed and applied to improve the piezoelectric capacity of cement-based composite, namely admixture incorporation and physical. The successful application of piezoelectric materials for sustainable building development not only relies on understanding the mechanism of the piezoelectric properties of various building components, but also the latest developments and implementations in the building industry. Therefore, this review systematically illustrates research efforts to develop new construction materials with high piezoelectricity and energy storage capacity. In addition, this article discusses the latest techniques for utilizing the piezoelectric materials in energy harvesters, sensors and actuators for various building systems. With advanced methods for improving the cementations piezoelectricity and applying the material piezoelectricity for different building functions, more renewable and sustainable building systems are anticipated.",book:{id:"10511",slug:"multifunctional-ferroelectric-materials",title:"Multifunctional Ferroelectric Materials",fullTitle:"Multifunctional Ferroelectric Materials"},signatures:"B. Chandra Sekhar, B. Dhanalakshmi, B. Srinivasa Rao, S. Ramesh, K. Venkata Prasad, P.S.V. Subba Rao and B. Parvatheeswara Rao",authors:[{id:"335022",title:"Dr.",name:"B. Chandra",middleName:null,surname:"Sekhar",slug:"b.-chandra-sekhar",fullName:"B. Chandra Sekhar"},{id:"422021",title:"Dr.",name:"B.",middleName:null,surname:"Dhanalakshmi",slug:"b.-dhanalakshmi",fullName:"B. Dhanalakshmi"},{id:"422022",title:"Dr.",name:"B.Srinivasa",middleName:null,surname:"Rao",slug:"b.srinivasa-rao",fullName:"B.Srinivasa Rao"},{id:"422023",title:"Dr.",name:"S.",middleName:null,surname:"Ramesh",slug:"s.-ramesh",fullName:"S. Ramesh"},{id:"422024",title:"Dr.",name:"K.Venkata",middleName:null,surname:"Prasad",slug:"k.venkata-prasad",fullName:"K.Venkata Prasad"},{id:"422025",title:"Dr.",name:"P.S.V",middleName:null,surname:"Subba Rao",slug:"p.s.v-subba-rao",fullName:"P.S.V Subba Rao"},{id:"422026",title:"Dr.",name:"B.Parvatheeswara",middleName:null,surname:"Rao",slug:"b.parvatheeswara-rao",fullName:"B.Parvatheeswara Rao"}]}],onlineFirstChaptersFilter:{topicId:"1169",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81438",title:"Research Progress of Ionic Thermoelectric Materials for Energy Harvesting",slug:"research-progress-of-ionic-thermoelectric-materials-for-energy-harvesting",totalDownloads:24,totalDimensionsCites:0,doi:"10.5772/intechopen.101771",abstract:"Thermoelectric material is a kind of functional material that can mutually convert heat energy and electric energy. It can convert low-grade heat energy (less than 130°C) into electric energy. Compared with traditional electronic thermoelectric materials, ionic thermoelectric materials have higher performance. The Seebeck coefficient can generate 2–3 orders of magnitude higher ionic thermoelectric potential than electronic thermoelectric materials, so it has good application prospects in small thermoelectric generators and solar power generation. According to the thermoelectric conversion mechanism, ionic thermoelectric materials can be divided into ionic thermoelectric materials based on the Soret effect and thermocouple effect. They are widely used in pyrogen batteries and ionic thermoelectric capacitors. The latest two types of ionic thermoelectric materials are in this article. The research progress is explained, and the problems and challenges of ionic thermoelectric materials and the future development direction are also put forward.",book:{id:"10037",title:"Thermoelectricity - Recent Advances, New Perspectives and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10037.jpg"},signatures:"Jianwei Zhang, Ying Xiao, Bowei Lei, Gengyuan Liang and Wenshu Zhao"},{id:"77670",title:"Thermoelectric Elements with Negative Temperature Factor of Resistance",slug:"thermoelectric-elements-with-negative-temperature-factor-of-resistance",totalDownloads:72,totalDimensionsCites:0,doi:"10.5772/intechopen.98860",abstract:"The method of manufacturing of ceramic materials on the basis of ferrites of nickel and cobalt by synthesis and sintering in controllable regenerative atmosphere is presented. As the generator of regenerative atmosphere the method of conversion of carbonic gas is offered. Calculation of regenerative atmosphere for simultaneous sintering of ceramic ferrites of nickel and cobalt is carried out. It is offered, methods of the dilated nonequilibrium thermodynamics to view process of distribution of a charge and heat along a thermoelement branch. The model of a thermoelement taking into account various relaxation times of a charge and warmth is constructed.",book:{id:"10037",title:"Thermoelectricity - Recent Advances, New Perspectives and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10037.jpg"},signatures:"Yuri Bokhan"},{id:"79236",title:"Processing Techniques with Heating Conditions for Multiferroic Systems of BiFeO3, BaTiO3, PbTiO3, CaTiO3 Thin Films",slug:"processing-techniques-with-heating-conditions-for-multiferroic-systems-of-bifeo3-batio3-pbtio3-catio",totalDownloads:96,totalDimensionsCites:0,doi:"10.5772/intechopen.101122",abstract:"In this chapter, we have report a list of synthesis methods (including both synthesis steps & heating conditions) used for thin film fabrication of perovskite ABO3 (BiFeO3, BaTiO3, PbTiO3 and CaTiO3) based multiferroics (in both single-phase and composite materials). The processing of high quality multiferroic thin film have some features like epitaxial strain, physical phenomenon at atomic-level, interfacial coupling parameters to enhance device performance. Since these multiferroic thin films have ME properties such as electrical (dielectric, magnetoelectric coefficient & MC) and magnetic (ferromagnetic, magnetic susceptibility etc.) are heat sensitive, i.e. ME response at low as well as higher temperature might to enhance the device performance respect with long range ordering. The magnetoelectric coupling between ferromagnetism and ferroelectricity in multiferroic becomes suitable in the application of spintronics, memory and logic devices, and microelectronic memory or piezoelectric devices. In comparison with bulk multiferroic, the fabrication of multiferroic thin film with different structural geometries on substrate has reducible clamping effect. A brief procedure for multiferroic thin film fabrication in terms of their thermal conditions (temperature for film processing and annealing for crystallization) are described. Each synthesis methods have its own characteristic phenomenon in terms of film thickness, defects formation, crack free film, density, chip size, easier steps and availability etc. been described. A brief study towards phase structure and ME coupling for each multiferroic system of BiFeO3, BaTiO3, PbTiO3 and CaTiO3 is shown.",book:{id:"10037",title:"Thermoelectricity - Recent Advances, New Perspectives and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10037.jpg"},signatures:"Kuldeep Chand Verma and Manpreet Singh"},{id:"78034",title:"Quantum Physical Interpretation of Thermoelectric Properties of Ruthenate Pyrochlores",slug:"quantum-physical-interpretation-of-thermoelectric-properties-of-ruthenate-pyrochlores",totalDownloads:78,totalDimensionsCites:0,doi:"10.5772/intechopen.99260",abstract:"Lead- and lead-yttrium ruthenate pyrochlores were synthesized and investigated for Seebeck coefficients, electrical- and thermal conductivity. Compounds A2B2O6.5+z with 0 ≤ z < 0.5 were defect pyrochlores and p-type conductors. The thermoelectric data were analyzed using quantum physical models to identify scattering mechanisms underlying electrical (σ) and thermal conductivity (κ) and to understand the temperature dependence of the Seebeck effect (S). In the metal-like lead ruthenates with different Pb:Ru ratios, σ (T) and the electronic thermal conductivity κe (T) were governed by ‘electron impurity scattering’, the lattice thermal conductivity κL (T) by the 3-phonon resistive process (Umklapp scattering). In the lead-yttrium ruthenate solid solutions (Pb(2-x)YxRu2O(6.5±z)), a metal–insulator transition occurred at 0.2 moles of yttrium. On the metallic side (<0.2 moles Y) ‘electron impurity scattering’ prevailed. On the semiconductor/insulator side between x = 0.2 and x = 1.0 several mechanisms were equally likely. At x > 1.5 the Mott Variable Range Hopping mechanism was active. S (T) was discussed for Pb-Y-Ru pyrochlores in terms of the effect of minority carrier excitation at lower- and a broadening of the Fermi distribution at higher temperatures. The figures of merit of all of these pyrochlores were still small (≤7.3 × 10−3).",book:{id:"10037",title:"Thermoelectricity - Recent Advances, New Perspectives and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10037.jpg"},signatures:"Sepideh Akhbarifar"},{id:"77635",title:"Optimization of Thermoelectric Properties Based on Rashba Spin Splitting",slug:"optimization-of-thermoelectric-properties-based-on-rashba-spin-splitting",totalDownloads:124,totalDimensionsCites:0,doi:"10.5772/intechopen.98788",abstract:"In recent years, the application of thermoelectricity has become more and more widespread. Thermoelectric materials provide a simple and environmentally friendly solution for the direct conversion of heat to electricity. The development of higher performance thermoelectric materials and their performance optimization have become more important. Generally, to improve the ZT value, electrical conductivity, Seebeck coefficient and thermal conductivity must be globally optimized as a whole object. However, due to the strong coupling among ZT parameters in many cases, it is very challenging to break the bottleneck of ZT optimization currently. Beyond the traditional optimization methods (such as inducing defects, varying temperature), the Rashba effect is expected to effectively increase the S2σ and decrease the κ, thus enhancing thermoelectric performance, which provides a new strategy to develop new-generation thermoelectric materials. Although the Rashba effect has great potential in enhancing thermoelectric performance, the underlying mechanism of Rashba-type thermoelectric materials needs further research. In addition, how to introduce Rashba spin splitting into current thermoelectric materials is also of great significance to the optimization of thermoelectricity.",book:{id:"10037",title:"Thermoelectricity - Recent Advances, New Perspectives and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10037.jpg"},signatures:"Zhenzhen Qin"},{id:"75364",title:"Challenges in Improving Performance of Oxide Thermoelectrics Using Defect Engineering",slug:"challenges-in-improving-performance-of-oxide-thermoelectrics-using-defect-engineering",totalDownloads:214,totalDimensionsCites:0,doi:"10.5772/intechopen.96278",abstract:"Oxide thermoelectric materials are considered promising for high-temperature thermoelectric applications in terms of low cost, temperature stability, reversible reaction, and so on. Oxide materials have been intensively studied to suppress the defects and electronic charge carriers for many electronic device applications, but the studies with a high concentration of defects are limited. It desires to improve thermoelectric performance by enhancing its charge transport and lowering its lattice thermal conductivity. For this purpose, here, we modified the stoichiometry of cation and anion vacancies in two different systems to regulate the carrier concentration and explored their thermoelectric properties. Both cation and anion vacancies act as a donor of charge carriers and act as phonon scattering centers, decoupling the electrical conductivity and thermal conductivity.",book:{id:"10037",title:"Thermoelectricity - Recent Advances, New Perspectives and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10037.jpg"},signatures:"Jamil Ur Rahman, Gul Rahman and Soonil Lee"}],onlineFirstChaptersTotal:6},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"May 18th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:27,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:9,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",slug:"ana-isabel-flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",slug:"christian-palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. 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He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. 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He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",slug:"arli-aditya-parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",slug:"cesar-lopez-camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",slug:"shymaa-enany",fullName:"Shymaa Enany",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRqB9QAK/Profile_Picture_1626163237970",institutionString:null,institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]},overviewPageOFChapters:{paginationCount:17,paginationItems:[{id:"81791",title:"Self-Supervised Contrastive Representation Learning in Computer Vision",doi:"10.5772/intechopen.104785",signatures:"Yalin Bastanlar and Semih Orhan",slug:"self-supervised-contrastive-representation-learning-in-computer-vision",totalDownloads:9,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Pattern Recognition - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11442.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"79345",title:"Application of Jump Diffusion Models in Insurance Claim Estimation",doi:"10.5772/intechopen.99853",signatures:"Leonard Mushunje, Chiedza Elvina Mashiri, Edina Chandiwana and Maxwell Mashasha",slug:"application-of-jump-diffusion-models-in-insurance-claim-estimation-1",totalDownloads:2,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Data Clustering",coverURL:"https://cdn.intechopen.com/books/images_new/10820.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"81557",title:"Object Tracking Using Adapted Optical Flow",doi:"10.5772/intechopen.102863",signatures:"Ronaldo Ferreira, Joaquim José de Castro Ferreira and António José Ribeiro Neves",slug:"object-tracking-using-adapted-optical-flow",totalDownloads:10,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Information Extraction and Object Tracking in Digital Video",coverURL:"https://cdn.intechopen.com/books/images_new/10652.jpg",subseries:{id:"24",title:"Computer Vision"}}},{id:"81558",title:"Thresholding Image Techniques for Plant Segmentation",doi:"10.5772/intechopen.104587",signatures:"Miguel Ángel Castillo-Martínez, Francisco Javier Gallegos-Funes, Blanca E. 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He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. 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He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. 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Chatterjee Memorial Research Prize-2019” and he is also the recipient of 'Dr.Raja Ramanna State Scientist Award 2015” by Government of Karnataka. He is a Fellow of the Royal Society of Biology (FRSB), London and Honorary Fellow of Karnataka Science and Technology Academy, Department of Science and Technology, Government of Karnataka.",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"243660",title:"Dr.",name:"Mallanagouda Shivanagouda",middleName:null,surname:"Biradar",slug:"mallanagouda-shivanagouda-biradar",fullName:"Mallanagouda Shivanagouda Biradar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243660/images/system/243660.jpeg",biography:"M. S. Biradar is Vice Chancellor and Professor of Medicine of\nBLDE (Deemed to be University), Vijayapura, Karnataka, India.\nHe obtained his MD with a gold medal in General Medicine and\nhas devoted himself to medical teaching, research, and administrations. He has also immensely contributed to medical research\non vascular medicine, which is reflected by his numerous publications including books and book chapters. Professor Biradar was\nalso Visiting Professor at Tulane University School of Medicine, New Orleans, USA.",institutionString:"BLDE (Deemed to be University)",institution:{name:"BLDE University",country:{name:"India"}}},{id:"289796",title:"Dr.",name:"Swastika",middleName:null,surname:"Das",slug:"swastika-das",fullName:"Swastika Das",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/289796/images/system/289796.jpeg",biography:"Swastika N. Das is Professor of Chemistry at the V. P. Dr. P. G.\nHalakatti College of Engineering and Technology, BLDE (Deemed\nto be University), Vijayapura, Karnataka, India. She obtained an\nMSc, MPhil, and PhD in Chemistry from Sambalpur University,\nOdisha, India. Her areas of research interest are medicinal chemistry, chemical kinetics, and free radical chemistry. She is a member\nof the investigators who invented a new modified method of estimation of serum vitamin E. She has authored numerous publications including book\nchapters and is a mentor of doctoral curriculum at her university.",institutionString:"BLDEA’s V.P.Dr.P.G.Halakatti College of Engineering & Technology",institution:{name:"BLDE University",country:{name:"India"}}},{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248459/images/system/248459.png",biography:"Akikazu Takada was born in Japan, 1935. After graduation from\nKeio University School of Medicine and finishing his post-graduate studies, he worked at Roswell Park Memorial Institute NY,\nUSA. He then took a professorship at Hamamatsu University\nSchool of Medicine. In thrombosis studies, he found the SK\npotentiator that enhances plasminogen activation by streptokinase. He is very much interested in simultaneous measurements\nof fatty acids, amino acids, and tryptophan degradation products. By using fatty\nacid analyses, he indicated that plasma levels of trans-fatty acids of old men were\nfar higher in the US than Japanese men. . He also showed that eicosapentaenoic acid\n(EPA) and docosahexaenoic acid (DHA) levels are higher, and arachidonic acid\nlevels are lower in Japanese than US people. By using simultaneous LC/MS analyses\nof plasma levels of tryptophan metabolites, he recently found that plasma levels of\nserotonin, kynurenine, or 5-HIAA were higher in patients of mono- and bipolar\ndepression, which are significantly different from observations reported before. In\nview of recent reports that plasma tryptophan metabolites are mainly produced by\nmicrobiota. He is now working on the relationships between microbiota and depression or autism.",institutionString:"Hamamatsu University School of Medicine",institution:{name:"Hamamatsu University School of Medicine",country:{name:"Japan"}}},{id:"137240",title:"Prof.",name:"Mohammed",middleName:null,surname:"Khalid",slug:"mohammed-khalid",fullName:"Mohammed Khalid",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/137240/images/system/137240.png",biography:"Mohammed Khalid received his B.S. degree in chemistry in 2000 and Ph.D. degree in physical chemistry in 2007 from the University of Khartoum, Sudan. He moved to School of Chemistry, Faculty of Science, University of Sydney, Australia in 2009 and joined Dr. Ron Clarke as a postdoctoral fellow where he worked on the interaction of ATP with the phosphoenzyme of the Na+/K+-ATPase and dual mechanisms of allosteric acceleration of the Na+/K+-ATPase by ATP; then he went back to Department of Chemistry, University of Khartoum as an assistant professor, and in 2014 he was promoted as an associate professor. In 2011, he joined the staff of Department of Chemistry at Taif University, Saudi Arabia, where he is currently an assistant professor. His research interests include the following: P-Type ATPase enzyme kinetics and mechanisms, kinetics and mechanisms of redox reactions, autocatalytic reactions, computational enzyme kinetics, allosteric acceleration of P-type ATPases by ATP, exploring of allosteric sites of ATPases, and interaction of ATP with ATPases located in cell membranes.",institutionString:"Taif University",institution:{name:"Taif University",country:{name:"Saudi Arabia"}}},{id:"63810",title:"Prof.",name:"Jorge",middleName:null,surname:"Morales-Montor",slug:"jorge-morales-montor",fullName:"Jorge Morales-Montor",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/63810/images/system/63810.png",biography:"Dr. Jorge Morales-Montor was recognized with the Lola and Igo Flisser PUIS Award for best graduate thesis at the national level in the field of parasitology. He received a fellowship from the Fogarty Foundation to perform postdoctoral research stay at the University of Georgia. He has 153 journal articles to his credit. He has also edited several books and published more than fifty-five book chapters. He is a member of the Mexican Academy of Sciences, Latin American Academy of Sciences, and the National Academy of Medicine. He has received more than thirty-five awards and has supervised numerous bachelor’s, master’s, and Ph.D. students. Dr. Morales-Montor is the past president of the Mexican Society of Parasitology.",institutionString:"National Autonomous University of Mexico",institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"217215",title:"Dr.",name:"Palash",middleName:null,surname:"Mandal",slug:"palash-mandal",fullName:"Palash Mandal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217215/images/system/217215.jpeg",biography:null,institutionString:"Charusat University",institution:null},{id:"49739",title:"Dr.",name:"Leszek",middleName:null,surname:"Szablewski",slug:"leszek-szablewski",fullName:"Leszek Szablewski",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49739/images/system/49739.jpg",biography:"Leszek Szablewski is a professor of medical sciences. He received his M.S. in the Faculty of Biology from the University of Warsaw and his PhD degree from the Institute of Experimental Biology Polish Academy of Sciences. He habilitated in the Medical University of Warsaw, and he obtained his degree of Professor from the President of Poland. Professor Szablewski is the Head of Chair and Department of General Biology and Parasitology, Medical University of Warsaw. Professor Szablewski has published over 80 peer-reviewed papers in journals such as Journal of Alzheimer’s Disease, Biochim. Biophys. Acta Reviews of Cancer, Biol. Chem., J. Biomed. Sci., and Diabetes/Metabol. Res. Rev, Endocrine. He is the author of two books and four book chapters. He has edited four books, written 15 scripts for students, is the ad hoc reviewer of over 30 peer-reviewed journals, and editorial member of peer-reviewed journals. Prof. Szablewski’s research focuses on cell physiology, genetics, and pathophysiology. He works on the damage caused by lack of glucose homeostasis and changes in the expression and/or function of glucose transporters due to various diseases. He has given lectures, seminars, and exercises for students at the Medical University.",institutionString:"Medical University of Warsaw",institution:{name:"Medical University of Warsaw",country:{name:"Poland"}}},{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"195136",title:"Dr.",name:"Aya",middleName:null,surname:"Adel",slug:"aya-adel",fullName:"Aya Adel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/195136/images/system/195136.jpg",biography:"Dr. Adel works as an Assistant Lecturer in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. Dr. Adel is especially interested in joint attention and its impairment in autism spectrum disorder",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"94911",title:"Dr.",name:"Boulenouar",middleName:null,surname:"Mesraoua",slug:"boulenouar-mesraoua",fullName:"Boulenouar Mesraoua",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94911/images/system/94911.png",biography:"Dr Boulenouar Mesraoua is the Associate Professor of Clinical Neurology at Weill Cornell Medical College-Qatar and a Consultant Neurologist at Hamad Medical Corporation at the Neuroscience Department; He graduated as a Medical Doctor from the University of Oran, Algeria; he then moved to Belgium, the City of Liege, for a Residency in Internal Medicine and Neurology at Liege University; after getting the Belgian Board of Neurology (with high marks), he went to the National Hospital for Nervous Diseases, Queen Square, London, United Kingdom for a fellowship in Clinical Neurophysiology, under Pr Willison ; Dr Mesraoua had also further training in Epilepsy and Continuous EEG Monitoring for two years (from 2001-2003) in the Neurophysiology department of Zurich University, Switzerland, under late Pr Hans Gregor Wieser ,an internationally known epileptologist expert. \n\nDr B. Mesraoua is the Director of the Neurology Fellowship Program at the Neurology Section and an active member of the newly created Comprehensive Epilepsy Program at Hamad General Hospital, Doha, Qatar; he is also Assistant Director of the Residency Program at the Qatar Medical School. \nDr B. Mesraoua's main interests are Epilepsy, Multiple Sclerosis, and Clinical Neurology; He is the Chairman and the Organizer of the well known Qatar Epilepsy Symposium, he is running yearly for the past 14 years and which is considered a landmark in the Gulf region; He has also started last year , together with other epileptologists from Qatar, the region and elsewhere, a yearly International Epilepsy School Course, which was attended by many neurologists from the Area.\n\nInternationally, Dr Mesraoua is an active and elected member of the Commission on Eastern Mediterranean Region (EMR ) , a regional branch of the International League Against Epilepsy (ILAE), where he represents the Middle East and North Africa(MENA ) and where he holds the position of chief of the Epilepsy Epidemiology Section; Dr Mesraoua is a member of the American Academy of Neurology, the Europeen Academy of Neurology and the American Epilepsy Society.\n\nDr Mesraoua's main objectives are to encourage frequent gathering of the epileptologists/neurologists from the MENA region and the rest of the world, promote Epilepsy Teaching in the MENA Region, and encourage multicenter studies involving neurologists and epileptologists in the MENA region, particularly epilepsy epidemiological studies. \n\nDr. Mesraoua is the recipient of two research Grants, as the Lead Principal Investigator (750.000 USD and 250.000 USD) from the Qatar National Research Fund (QNRF) and the Hamad Hospital Internal Research Grant (IRGC), on the following topics : “Continuous EEG Monitoring in the ICU “ and on “Alpha-lactoalbumin , proof of concept in the treatment of epilepsy” .Dr Mesraoua is a reviewer for the journal \"seizures\" (Europeen Epilepsy Journal ) as well as dove journals ; Dr Mesraoua is the author and co-author of many peer reviewed publications and four book chapters in the field of Epilepsy and Clinical Neurology",institutionString:"Weill Cornell Medical College in Qatar",institution:{name:"Weill Cornell Medical College in Qatar",country:{name:"Qatar"}}},{id:"282429",title:"Prof.",name:"Covanis",middleName:null,surname:"Athanasios",slug:"covanis-athanasios",fullName:"Covanis Athanasios",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/282429/images/system/282429.jpg",biography:null,institutionString:"Neurology-Neurophysiology Department of the Children Hospital Agia Sophia",institution:null},{id:"190980",title:"Prof.",name:"Marwa",middleName:null,surname:"Mahmoud Saleh",slug:"marwa-mahmoud-saleh",fullName:"Marwa Mahmoud Saleh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190980/images/system/190980.jpg",biography:"Professor Marwa Mahmoud Saleh is a doctor of medicine and currently works in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. She got her doctoral degree in 1991 and her doctoral thesis was accomplished in the University of Iowa, United States. Her publications covered a multitude of topics as videokymography, cochlear implants, stuttering, and dysphagia. She has lectured Egyptian phonology for many years. Her recent research interest is joint attention in autism.",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259190/images/system/259190.png",biography:"Dr. Naqvi is a radioanalytical chemist and is working as an associate professor of analytical chemistry in the Department of Chemistry, Government College University, Faisalabad, Pakistan. Advance separation techniques, nuclear analytical techniques and radiopharmaceutical analysis are the main courses that he is teaching to graduate and post-graduate students. In the research area, he is focusing on the development of organic- and biomolecule-based radiopharmaceuticals for diagnosis and therapy of infectious and cancerous diseases. Under the supervision of Dr. Naqvi, three students have completed their Ph.D. degrees and 41 students have completed their MS degrees. He has completed three research projects and is currently working on 2 projects entitled “Radiolabeling of fluoroquinolone derivatives for the diagnosis of deep-seated bacterial infections” and “Radiolabeled minigastrin peptides for diagnosis and therapy of NETs”. He has published about 100 research articles in international reputed journals and 7 book chapters. Pakistan Institute of Nuclear Science & Technology (PINSTECH) Islamabad, Punjab Institute of Nuclear Medicine (PINM), Faisalabad and Institute of Nuclear Medicine and Radiology (INOR) Abbottabad are the main collaborating institutes.",institutionString:"Government College University",institution:{name:"Government College University, Faisalabad",country:{name:"Pakistan"}}},{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",country:{name:"Hungary"}}},{id:"277367",title:"M.Sc.",name:"Daniel",middleName:"Martin",surname:"Márquez López",slug:"daniel-marquez-lopez",fullName:"Daniel Márquez López",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/277367/images/7909_n.jpg",biography:"Msc Daniel Martin Márquez López has a bachelor degree in Industrial Chemical Engineering, a Master of science degree in the same área and he is a PhD candidate for the Instituto Politécnico Nacional. His Works are realted to the Green chemistry field, biolubricants, biodiesel, transesterification reactions for biodiesel production and the manipulation of oils for therapeutic purposes.",institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. He is the co-editor of The Open Biology Journal and associate editor for Oxidative Medicine and Cellular Longevity.",institutionString:"Universidad Nacional de La Plata",institution:{name:"National University of La Plata",country:{name:"Argentina"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",biography:"Francisco Javier Martín-Romero (Javier) is a Professor of Biochemistry and Molecular Biology at the University of Extremadura, Spain. He is also a group leader at the Biomarkers Institute of Molecular Pathology. Javier received his Ph.D. in 1998 in Biochemistry and Biophysics. At the National Cancer Institute (National Institute of Health, Bethesda, MD) he worked as a research associate on the molecular biology of selenium and its role in health and disease. After postdoctoral collaborations with Carlos Gutierrez-Merino (University of Extremadura, Spain) and Dario Alessi (University of Dundee, UK), he established his own laboratory in 2008. The interest of Javier's lab is the study of cell signaling with a special focus on Ca2+ signaling, and how Ca2+ transport modulates the cytoskeleton, migration, differentiation, cell death, etc. He is especially interested in the study of Ca2+ channels, and the role of STIM1 in the initiation of pathological events.",institutionString:null,institution:{name:"University of Extremadura",country:{name:"Spain"}}},{id:"217323",title:"Prof.",name:"Guang-Jer",middleName:null,surname:"Wu",slug:"guang-jer-wu",fullName:"Guang-Jer Wu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217323/images/8027_n.jpg",biography:null,institutionString:null,institution:null},{id:"148546",title:"Dr.",name:"Norma Francenia",middleName:null,surname:"Santos-Sánchez",slug:"norma-francenia-santos-sanchez",fullName:"Norma Francenia Santos-Sánchez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/148546/images/4640_n.jpg",biography:null,institutionString:null,institution:null},{id:"272889",title:"Dr.",name:"Narendra",middleName:null,surname:"Maddu",slug:"narendra-maddu",fullName:"Narendra Maddu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272889/images/10758_n.jpg",biography:null,institutionString:null,institution:null},{id:"242491",title:"Prof.",name:"Angelica",middleName:null,surname:"Rueda",slug:"angelica-rueda",fullName:"Angelica Rueda",position:"Investigador Cinvestav 3B",profilePictureURL:"https://mts.intechopen.com/storage/users/242491/images/6765_n.jpg",biography:null,institutionString:null,institution:null},{id:"88631",title:"Dr.",name:"Ivan",middleName:null,surname:"Petyaev",slug:"ivan-petyaev",fullName:"Ivan Petyaev",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Lycotec (United Kingdom)",country:{name:"United Kingdom"}}},{id:"423869",title:"Ms.",name:"Smita",middleName:null,surname:"Rai",slug:"smita-rai",fullName:"Smita Rai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424024",title:"Prof.",name:"Swati",middleName:null,surname:"Sharma",slug:"swati-sharma",fullName:"Swati Sharma",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"439112",title:"MSc.",name:"Touseef",middleName:null,surname:"Fatima",slug:"touseef-fatima",fullName:"Touseef Fatima",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424836",title:"Dr.",name:"Orsolya",middleName:null,surname:"Borsai",slug:"orsolya-borsai",fullName:"Orsolya Borsai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca",country:{name:"Romania"}}},{id:"422262",title:"Ph.D.",name:"Paola Andrea",middleName:null,surname:"Palmeros-Suárez",slug:"paola-andrea-palmeros-suarez",fullName:"Paola Andrea Palmeros-Suárez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Guadalajara",country:{name:"Mexico"}}}]}},subseries:{item:{id:"27",type:"subseries",title:"Multi-Agent Systems",keywords:"Collaborative Intelligence, Learning, Distributed Control System, Swarm Robotics, Decision Science, Software Engineering",scope:"Multi-agent systems are recognised as a state of the art field in Artificial Intelligence studies, which is popular due to the usefulness in facilitation capabilities to handle real-world problem-solving in a distributed fashion. The area covers many techniques that offer solutions to emerging problems in robotics and enterprise-level software systems. Collaborative intelligence is highly and effectively achieved with multi-agent systems. Areas of application include swarms of robots, flocks of UAVs, collaborative software management. Given the level of technological enhancements, the popularity of machine learning in use has opened a new chapter in multi-agent studies alongside the practical challenges and long-lasting collaboration issues in the field. It has increased the urgency and the need for further studies in this field. We welcome chapters presenting research on the many applications of multi-agent studies including, but not limited to, the following key areas: machine learning for multi-agent systems; modeling swarms robots and flocks of UAVs with multi-agent systems; decision science and multi-agent systems; software engineering for and with multi-agent systems; tools and technologies of multi-agent systems.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/27.jpg",hasOnlineFirst:!1,hasPublishedBooks:!1,annualVolume:11423,editor:{id:"148497",title:"Dr.",name:"Mehmet",middleName:"Emin",surname:"Aydin",slug:"mehmet-aydin",fullName:"Mehmet Aydin",profilePictureURL:"https://mts.intechopen.com/storage/users/148497/images/system/148497.jpg",biography:"Dr. Mehmet Emin Aydin is a Senior Lecturer with the Department of Computer Science and Creative Technology, the University of the West of England, Bristol, UK. His research interests include swarm intelligence, parallel and distributed metaheuristics, machine learning, intelligent agents and multi-agent systems, resource planning, scheduling and optimization, combinatorial optimization. Dr. Aydin is currently a Fellow of Higher Education Academy, UK, a member of EPSRC College, a senior member of IEEE and a senior member of ACM. In addition to being a member of advisory committees of many international conferences, he is an Editorial Board Member of various peer-reviewed international journals. He has served as guest editor for a number of special issues of peer-reviewed international journals.",institutionString:null,institution:{name:"University of the West of England",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null,series:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403"},editorialBoard:[{id:"275140",title:"Dr.",name:"Dinh Hoa",middleName:null,surname:"Nguyen",slug:"dinh-hoa-nguyen",fullName:"Dinh Hoa Nguyen",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRbnKQAS/Profile_Picture_1622204093453",institutionString:null,institution:{name:"Kyushu University",institutionURL:null,country:{name:"Japan"}}},{id:"20259",title:"Dr.",name:"Hongbin",middleName:null,surname:"Ma",slug:"hongbin-ma",fullName:"Hongbin Ma",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRhDJQA0/Profile_Picture_2022-05-02T08:25:21.jpg",institutionString:null,institution:{name:"Beijing Institute of Technology",institutionURL:null,country:{name:"China"}}},{id:"28640",title:"Prof.",name:"Yasushi",middleName:null,surname:"Kambayashi",slug:"yasushi-kambayashi",fullName:"Yasushi Kambayashi",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYOQxQAO/Profile_Picture_1625660525470",institutionString:null,institution:{name:"Nippon Institute of Technology",institutionURL:null,country:{name:"Japan"}}}]},onlineFirstChapters:{paginationCount:17,paginationItems:[{id:"81647",title:"Diabetes and Epigenetics",doi:"10.5772/intechopen.104653",signatures:"Rasha A. 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