Panel data analysis of the impact of economic level (GDP, health expenditure, unemployment, and poverty) on SCI.
\r\n\tThis book chapter’s main theme will be focused on transmission dynamics, pathogenesis, mechanisms of host interaction and response, epigenetics and markers, molecular diagnosis, RNA interacting proteins, RNA binding proteins, advanced development of tools for diagnosis, possible development of concepts for vaccines and anti drugs for RNA viruses, immunological mechanisms, treatment, prevention and control.
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In recent years, with the developments of the laser technology, femtosecond laser technology is becoming more and more consummate as a novel technology. Femtosecond laser pulse is also becoming into a powerful tool for microfabrication and micro-machining of various multi-functional structures in dielectric materials through multi-photon absorption because of its high-quality and damage-free processing. Up to now, many high-quality material processing techniques have been achieved by using femtosecond laser pulses with the methods of directly writing [1-10] and holographic fabrication [11-22], such as waveguide [1], special diffractive optical elements (DOE) [4-10], micro-gratings [11-15], and photonic crystals [16-20]. Because multiphoton nonlinear effects play a major role in this process, the resulting change in refractive index or cavity formation can be highly localized only in the focal volume where the fluence is above a certain material dependent threshold, which makes it possible to micro-fabricate devices inside the bulk of transparent materials. These structures were usually fabricated with a focused beam and written dot by dot by translation of the sample with respect to the focal point.
Compared to directly writing technology by femtosecond laser pulses, holographic lithography has been considered as a more effective method for fabricating periodic structures because it can be controlled easily by the number of the beam, angles between every two beams, energies of the laser beams, and most importantly, only one pulse needed for holographic fabrication. Especially, holographic lithography is considered to be the most effective method for the fabrication of the photonic crystals. And Cai
There are also many groups who have attempted to fabricate the periodic structures in photosensitive transparent materials or on the surface of the silica glass and the metal film by interfered multiple femtosecond laser pulses. Especially, it is very easy to fabricate the periodic structures inside of the photosensitive transparent materials with the aid of diffractive beam-splitter (DBS) [18-20]. However it is limited by the angles between two beams and the energy of the pulses. It is therefore difficult to fabricate microstructure with smaller period, especially in the materials with big band gap, such as silica glass. So there are also some researching groups [13, 16-17] focusing on the realization of periodic structures on the surface of the silica glass by a single shot of two or three femtosecond laser pulses originating from one pulse by the beam splitters.
Computer simulations of four Bravais lattices formed by interference of four noncoplanar beams: (a) face-centered cubic lattice, (b) body-centered cubic lattice, (c) hexagonal lattice (
In this chapter, we have reviewed the progress of fabrication of the periodic structures on the surface or inside of the transparent silica glass by a single shot of several (two, three, four) femtosecond laser pulses. When a single shot of two pulses interfered with each other, there will be one dimensional grating structures being formed inside of the photosensitive transparent materials or on the surface of the materials. When a single shot of three coplanar pulses interfered with each other, the one-dimensional M-shape grating can be formed on the surface of the silica glass. However, when a single shot of noncoplanar three or four pulses interfered with each other, two-dimensional periodic microstructure can be obtained, which distributed as a hexagonal lattice or tetragonal lattice.
The experimental setup for the holographic fabrication of microgratings by a single shot of two interfered femtosecond laser pulses is depicted in Fig. 2 (a). A regeneratively amplified Ti:sapphire laser (Coherent. Co.) with a central wavelength of 800 nm, pulse duration of 120 fs, and pulse repetition of 1–1000 Hz was used. A single femtosecond laser pulse with a beam diameter of 6 mm could be selected and split into two pulses that were then redirected at controllable incident angles on the surface of the fused silica glass (K9 glass) which is transparent for the laser with a wavelength of 800 nm. These split pulses generating from the single pulse were focused on the glass surface by two lenses with focal lengths of 20 cm to give a spot size of ~50 μm at the focal plane. Attenuators could be used to obtain a proper energy of the pulses for controlling the results of the holographic fabrication. The two pulses could be adjusted both spatially and temporarily by the optical delay device perfectly. The angle between two pulse and the pulse energies could be controlled easily.
When we set the angle between the split beams as 40o and the pulse energy as 45 μJ, the fabricated grating is shown in the Fig. 2 (b-e) by optical microscopy and atomic force microscopy (AFM) respectively. From the Fig. 2 (d), we can obtain the period of the fabricated grating is about 1.06 μm which agree well with the calculated result according to the formula d=λ/[2sin(θ/2)] in which θ is colliding angle (θ=40o in this experiment) between two incident beams and λ is the incident laser wavelength of 800
However, when we set the angle θ as 20o and the pulse energy as 65 μJ, the fabricated grating is shown in the Fig. 3. Not only did we get the ordinary grating whose periods accorded with the theoretic equation d=λ/[2sin(θ/2)], but also obtained the extraordinary grating [15, 23] whose period is a half of the ordinary grating. The extraordinary grating formed at the middle of each bulge of the ordinary grating as shown in Fig. 3 (a-b), so the period of the extraordinary grating is a half of the ordinary grating’s observed easily from Fig. 3(c) which also shows that the depth of the extraordinary grating is a half of the ordinary grating’s nearly.
In the experiments, with the decrease of the incident energy in the same angle between two beams, the modulation depths of the extraordinary grating are decreasing gradually. With the increase of the angle between two beams with the same energy, the modulation depths of the extraordinary grating are also decreasing gradually. At last the modulation will be vanishing from the central part to the edge of the ordinary grating gradually.
The experimental setup for the holographic fabrication of microgratings, (b) the fabricated grating observed by optical microscopy, (c) top-viewing AFM image of the fabricated grating, (d) cross-section view in the direction of black line shown in (c), (e) three dimentional view of the fabricated structure.
The formation of the modulation grating could be attributed to the higher-order modulation arising from second-harmonic generation (SHG) when the femtosecond laser pulse was incident to the surface of silica glass. As a rule, because of the inversion symmetry of the silica glass, there should be no second order nonlinearity in the silicon glass. However, a layer of plasma could be formed on the surface of the glass when the pulse incident to the sample because of the ultra high electrical field of the femtosecond laser in a time given by the duration of the laser pulse[24,25]. Therefore, when the femtosecond laser pulse with high intensity is incident on this thin plasma layer, there will be the higher harmonic generation because of the electrons quivering nonlinearly, and the SHG can reach to 2% of the fundamental laser [26]. The second-harmonic radiation is emitted in the direction of the reflected fundamental laser direction as depicted in Fig. 2 (d) [24]. So the period of the modulation grating is a half of the common grating because of the same of the angle between the two beams but a half of the wavelength. Although the intensity of the SHG is much smaller than the fundamental laser, the modulated depth of the silica glass can reach to a correspondingly large depth because it is much easier for the silica glass to be ionized by a mechanism of single or two photons absorption than multiphoton absorption.
AFM photos of the resulted micrograting encoded with an energy of ~65 μJ for each interfered beam and a colliding angle of ~20°. (a) Image of the central portion of the grating, (b) an enlarged version for the chosen part in (a), and
Li
The multiple gratings were written inside of the soda–lime glass one after another by focusing the beam 1 and beam 2 into special position inside of the glass sample with the recording plane. Without loss of generality, three layers of micrograting could be recorded at depths of 200, 400, and 600 μm, respectively. The grating at depth of 600μm should be encoded firstly. Then the sample was translated along the
Because the micrograting was formed inside of the samples around the focal point without damage to the surface or other parts of the sample, multiple layers of grating can be recorded successfully. And the images of the fabricated multiple layers of microgratings could be read out by beam 2 and taken over three different recording planes as depicted in Fig. 4 (b) and (c). The schematics on the right illustrate the relative positions of the sample, three layers of grating, the recording plane, and the objective. The experimental results demonstrated that the readout image of the first layer (not shown here) and the second layer (as depicted in Fig. 4 (b)) of the recorded grating consisted of well-defined straight bright lines alternating with black lines. However, for the readout of the third layer of the micrograting, some of the straight lines became curved as shown in Fig. 4 (c). This aberration may be caused by the wave-front distortion of the incident beams due to the accumulation of nonlinear effects when the focused high peak-power pulse propagated through the sample. The longer the optical path inside the sample was, the more severe the wave-front distortion and the more obvious the resulting grating aberration.
(a) Top view of the experimental setup for the formation of multiple gratings inside glass. The recording plane is in the
Noble metal nanoparticle-contained glasses exhibit large third-order nonlinear susceptibility and ultrafast nonlinear response due to the local field effect near surface Plasmon resonance and quantum size effect [27, 28]. In recent years, many studies have been carried out on the fabrication of nanoparticle-doped glasses [29-31]. Shiliang Qu
A typical silicate glass is composed of 70SiO2.20Na2O.10CaO doped with 0.1Au2O (mol%). Reagent grade SiO2, CaCO3, Na2CO3, and AuCl3.HCl.4H2O were used as starting materials. An approximately 40g batch was mixed and placed into a platinum crucible. Melting was carried out in an electric furnace at 1550 °C for 1 h. The glass sample was obtained by quenching the melt to room temperature. The sample thus obtained was transparent and colorless. The annealed sample was cut and polished, and then subjected to successive experiments for femtosecond laser.
Optical microscopic photos of Au nanoparticles precipitation in periodic arrays in silicate glass (microgratings), taken by a 100X transilluminated optical microscope. (a) Energy is 30 μJ per pulse. (b) Magnified view of (a). (c) Energy is 38μJ per pulse. (d) Part of a group of formed microgratings array inside of the sample. (e) Absorption spectra of the glass samples after holographic irradiation by femtosecond laser pulses with (line a) and without (line b) heat treatment.
The used laser system and the experimental setup are the same as the used setup as shown in Fig. 2 (a). The two incident beams were first focused onto the front surface of Au2O-doped glass to optimize the incident pulse energy. In the case of sufficiently high energy, the two coherent beams can induce periodic ablation, forming a grating in the glass. Herein, we reduced the incident pulses’ energy to a certain lower level at which the two coherent beams cannot directly induce periodic ablation on the surface of the glass. Then the sample was moved 50μm to the lens in the direction of angular bisector of two incident light paths and made the laser pulses be focused inside the glass. After irradiation by a single shot of two interfered pulses, the micrograting can be recorded inside the glass, which can not be observed immediately because there is no obvious changes in the focusing place, however, after heat treating the sample at 550 °C for 1 h, the formed micrograting can be observed because of the Au nanoparticle precipitation. Such grating was constituted by the laser-heating induced Au nanoparticle precipitation in the Au2O-doped glass.
In Qu’s experiments, this lower pulse energy was selected to be 30 and 38 μJ for comparison, and the colliding angle θ between the two incident beams was fixed at 45°. The fabricated micrograting is shown in Fig.5 (a-d). The period d of the obtained gratings was about ~1μm which was agreeing well with the value calculated from the colliding angle θ and the laser wavelength λ according to the formula d=λ/[2sin(θ/2)].
The absorption spectrum of the grating was measured by a spectrophotometer (JASCOV-570) as shown in Fig. 5 (e) (line a). Apparently, a weak peak occurs around 508 nm, which is induced by the surface plasmon resonance of Au nanoparticles in the glass. The Au nanoparticles with 3 nm average size in the glass were observed in the grid of the fabricated micrograting from a transmitted electronic microscopy (TEM). However, if the glass sample was irradiated only by the interfered pulses but not heat treated, neither could absorption peak in the range of 500–600 nm be observed in the absorption spectrum as shown in Fig. 5 (e) (line b), nor could Au nanoparticles be observed by the TEM. This indicates that the Au nanoparticles can be precipitated in the periodic one-dimensional arrays in the glass through the irradiation of two coherent beams with the aid of heat treatment.
The interference of two laser beams can create microstructures with one-dimensional periodic patterns in certain materials due to the periodic modulation of the laser intensity with a period scale of the order of the laser wavelength. As stated as above, there has been many groups focusing the fabrication of microgratings in glasses [11, 12], thin films [32], polymers[33], and inorganic–organic hybrid materials [34] by use of two interfered femtosecond laser pulses in a single shot. However, there is a disadvantage for micrograting fabrication with this method: Only a single micrograting can be formed for one pulse. Shiliang Qu
In the experimental setup as shown in Fig. 6 (a) which is similar with the Fig. 2 (a) and\n\t\t\t\t\tFig. 4 (a), a regeneratively amplified Ti:sapphire laser (Spectra-Physics) with a wavelength of 800 nm, pulse duration of 120 fs, and pulse repetition of 1–1000 Hz was used. A single laser pulse with a beam diameter of 8 mm was selected and split into two beams that were then redirected at approximately equal incident angles on a silicate glass surface. The two beams were focused on the glass surface by two lenses with focal lengths of 10 cm (L1) and 20 cm (L2) to yield spot sizes of 40μm and 80μm, respectively.
The colliding angle θ between the two beams was fixed at 40o. After the optical paths were adjusted to realize perfect overlap of the two beams both spatially and temporally, the surface of the glass was adjusted to be approximately normal to the perpendicular bisector of the two incident beams, so that the glass surface became the laser interfering plane. A mask used for laser beam modulation was placed in the optical path in which lens L1 is located. The mask consists of three equilaterally and triangularly arrayed apertures, whose diameters are 2.5 mm and the spaces between them are 3.5 mm as shown in Fig. 6(b).
Experimental setup for the one-off writing of multi-microgratings by a single shot of two femtosecond laser pulses. M’s, mirrors; BS, beam splitter. (b) Data mask for multimicrograting formation. (c) Optical microscopic observation of a multi-micrograting formed on silicate glass with a period of 1.1μm (
After irradiation by one single shot of two interfered pulses, the multi-micrograting comprises three microgratings as shown in Fig. 6(c), which has a high fidelity to the configuration of the mask used. The multi-micrograting was formed through periodic ablation resulting from the interference of the reference laser beam with the three beams caused by the mask. And the period of the formed microgratings is also agree well with the theoretical expectation of the common grating d=λ/[2sin(θ/2)]. This means that a multi-micrograting comprising even more microgratings and configurations can also be one-off written by changing only the mask structure. However, multi-micrograting formation can be realized only when the two interfered beams are overlapped at an appropriate position out of their focus on the front surface of the glass.
As stated above, two interfered femtosecond pulses’ interference can induce one and two-dimensional periodic structures by single and double-exposure techniques, respectively [11−15, 40]. However, usually the second pulse could not overlap completely with the microstructure formed by the first pulse in the double-exposure technique due to the rather small size of the focal spot. Here, we will show that the fabrication of M-shape gratings with controllable modulation depth could be realized by adding the third beam into a two-beam interference system. The experimental results show that the depth ratio between neighbor grooves can be conveniently controlled by changing the pulse energy of the third beam. Morphology characterizations of as-fabricated periodic M-shape gratings with a period of 2
Experimental setup of three-beam interference optical system (AT and AP stand for attenuator and aperture, respectively).
The schematic experimental setup for fabricating M-shape grating is shown in Fig.7. The used ultrafast pulses (with a pulse width of 120 fs, central wavelength of 800 nm, and repetition rate of 1–1000 Hz) are produced by a Ti: sapphire regenerative amplified laser system (Coherent Inc). A laser pulse with a diameter of
The optical microscope images of the gratings formed on the silica glass at different pulse energies of L2 (
Optical microscope images of as-formed gratings by coplanar three-beam interference with different pulse energies of L2, i.e. (a) 50 μJ and (b) 100 μJ. AFM images of the M-shape grating formed on silica glass by three coplanar interfering beams, each with equal energy of 50 μJ, the collision angles of three beams are 18
It is obviously shown that the structure is formed by periodically arranging the M-shape units with a size of about 2.6 μm. The modulation depths of the deeper grooves and shallower grooves of the M-shape grating are ~500 nm and ~240 nm, respectively. The deeper grooves and the shallower grooves of the M-shape grating each have a period of
Intensity distributions simulated by using three interfering coplanar beams with different pulse energies of L2 ( (a), (b), and (c)) and L3 ((d), (e), and (f)), where k = 2π/λ, λ = 800 nm, θ = 18◦ and different values of I01, I02 and I03, i.e. (a) I01 = 2.12, I02 = 0.85, and I03 = 2.12, (b) I01 = 2.12, I02 = 2.12, and I03 = 2.12, (c) I01 = 2.12, I02 = 4.24, and I03 = 2.12, (d) I01 = 2.12, I02 = 2.12, and I03 = 2.12, (e) I01 = 2.12, I02 = 2.12, and I03 = 1.06, and (f) I01 = 2.12, I02 = 2.12, and I03 = 0.53, which are all in units of 1013 W/cm2.
The simulated intensity distributions in the interfering region formed by three coplanar interfering beams are shown in Figs. 9 (a), (b) and (c), which correspond to the middle beam (L2) pulse energies of 20 μJ, 50 μJ and 100 μJ, respectively. In Figs. 9 (a), (b) and (c), the upper images show the three-dimensional patterns and the nether curves display the two-dimensional cross-section patterns. From the cross-section images of Figs. 9 (a-c), we can see clearly that the periodic intensity patterns are formed by the periodic arrangement of inversely M-shape structures, which is attributed to stronger intensity peaks and weaker ones arrayed with the same period of about 2.6 μm alternately and periodically. These results are consistent with the AFM results as shown in Fig. 8. We notice that with the energy of the middle pulses increasing, the stronger intensity peaks in the interfering region increase, while the weaker intensity peaks decrease. It indicates that the intensity ratio of the stronger peak and the weaker one increases. If laser pulses with such a periodic inversely M-shape intensity distribution irradiate the materials, the stronger intensity peaks will lead to the formation of deeper grooves, and the weaker intensity peaks will induce the formation of shallower ones. As a result, the M-shape surface structures will be resultantly formed. This fabricating technology for the formation of M-shape gratings provides a fabricating method for special gratings with special use in industrial applications, such as the calibration for 3D reconstruction in computer vision application. And the fabricated M-shape grating can also be used in microfluidic chip devices as transport channels with different flowing speeds.
When a single shot of three coplanar pulses interfered with each other, the M-shaped gratings could be fabricated as above. However, when a single shot of three non-coplanar pulses interfered with each other as depicted in Fig. 10 (a) by adjusting two time-delay for obtaining perfect overlap of the three pulses both spatially and temporarily, the two-dimensional periodic microstructure have been obtained, which distributed as a hexagonal lattice as shown in Fig. 10 (b) and agreed well with the simulated results [see Fig. 10 (c)] [16, 17]. In experiments, the geometric angles were kept as θ=300 and ϕ=350 respectively as shown in Fig. 10 (a). When we set the pulse energy as 75 μJ, we can obtain two-dimensional periodic hexagonal lattice of microholes [see Fig. 10 (d-f)], however, when we set the pulse energy as 30 μJ, the two dimensional periodic microstructures present doughnut orbicular platform [see Fig. 10 (g-i)]. The period in the direction of line “
The different microstructures in our experiments were attributed to the formation of plasma and molten liquid at different pulse energy levels. Generally it is hard to form plasma and molten liquid on the surface of silica glass by a laser with a wavelength of 800 nm because of the bigger band gap. However, the intensity at the focal point of the femtosecond laser beam where three beams interfere together could reach to 100 TW/cm2 nearly. Such a high-energy influence within the focal volume ionized the silica glass quickly through the combined action of the avalanche and multiphoton processes [17, 35]. A layer of plasma formed on the surface of the silica glass at the time of the laser pulse duration. While the intensity decreased to be lower than a certain value, which can be called the ionized threshold as shown in Fig. 11 (a), the plasma vanished and the molten liquid of the material appeared. With the decrease of the intensity to be lower than a certain value, which could be called the molten threshold [see Fig. 11 (a)], the molten liquid of the material disappeared, so there would be a doughnut molten liquid formed in every enhanced spot of the interfered field [see Fig. 11 (b)]
When the pulse energy was set as 75 μJ, a layer of modulated plasma was formed by the interfered field with hexagonal lattice depicted in Fig. 10 (c) after the anterior part of the pulse was incident to the surface of the silica glass. Higher intensity induced a relatively larger plasma area in every enhanced spot of the interfered field. The subsequent posterior part of the pulse removed the plasma very swiftly because of the high light pressure originating from the reflection. Therefore, the microholes formed on the surface of the silica glass, as depicted in Fig. 10 (d-f). When the pulse energy decreased to 30 μJ, there was just a layer of the plasma with smaller areas than that of 75 μJ in the center of every enhanced spot in the interfered field after the anterior part of the pulse was incident to the surface. The
(a) Geometric sketch of the three non-coplanar interfered beams, and the sample is laid in the
subsequent posterior part of the pulse also removed the central plasma very swiftly by means of light pressure, so there is a tiny hole formed in the center of the enhanced spot. However, in the region of the molten liquid, there were two distinct interaction components because of Marangoni effect, thermocapillary and chemicapillary, which resulted from the thermal potential of a temperature gradient and the chemical potential of a compositional gradient, respectively [17, 36-37]. The thermocapillary force moved the molten material outward from the center, while the chemicapillary force moved the molten material toward the center [38-39] as depicted in Fig. 10 (b). When the chemicapillary force dominated, a platform formed in the center of the spot. The combined action of the light pressure to the plasma and the chemicapillary force to the molten liquid induced a periodic orbicular platform on the surface of the silica glass as depicted in Fig. 10 (g-i).
(a) The intensity distribution of the enhanced spot in the interfered field by three non-coplanar beams, II and IM represent the densities of the ionized and molten thresholds respectively, (b) schematic diagram explanation for the mechanism of formed different structures owing to the formation of the plasma and Marangoni effect.
(a) AFM photo of the periodic structure induced by a single shot of three pulses with pulse energies of 50 μJ. Three-dimensional analyzed photos of the three selected parts I, II, and III in (a) are shown in (b)–(d) respectively.
In order to verify our explanation on the different induced microstructures, we set the pulses energy as 50 μJ, and the resulted microstructure is shown in Fig. 12 (a). Because of the Gaussian type intensity distribution of the pulse, three regions are selected from the central part (I), outer part (II) and the edge part (III) of the microstructure as depicted in Fig. 12 (a). The corresponding three dimensional images of the selected areas are shown in Fig. 12 [(b)-(d)], respectively. For the region I, the intensity is high enough to make the light pressure dominate, therefore the periodic microholes formed [see Fig. 12 (b)]. In contrast, in the region II, where the intensity is comparatively low, the chemicapillary force and the light pressure dominate, so that the microstructure present a orbicular platform [see Fig. 12 (c)]. However, in the selected area III, the intensity is very low and there is no plasma layer but just a layer of liquid formed on the surface of the silica glass. In this case, if the chemicapillary force dominates, the microcones can be observed. As shown in Fig. 12 (d), just several microcones (indicated by arrows) formed in the edge of the interfered districts.
The interference of two beams creates a one-dimensional (1D) periodic pattern. By increasing the number of beams [16-20] or the double-exposure techniques [40], in principle, two-dimensional (2D) and three-dimensional (3D) periodic patterns can be designed. Although, as stated above, the interference of the three beams [13, 16-17] can create a 1D [13] or 2D [16, 17] periodic pattern on the surface of the materials of inside the transparent materials, the complicated optical setup is required for the interference of multiple laser beams, and its precise adjustment is difficult. Kondo
(a) Optical setup. DBS: diffractive beam splitter, L1 and L2: lenses,AA: aperture array. The inset shows the absorption spectrum of 4-mm-thick SU-8 film spin-coated on a coverglass. (b) Calculated intensity distribution by the interference of four beams which have same phase, (c) phase of one beam is shifted by π.
The optical setup used for the present experiments is shown in Fig. 13(a). Briefly, a DBS (G1023A or G1025A; MEMS Optical Inc.) divides the input laser beam into several beams, and the beams are collected on the sample by two lenses. Temporal overlap of the divided pulses is achieved without adjusting the optical path lengths. Each beam was made to be parallel or slightly focused by the adjustment of the distance between the two lenses. Slight focusing increased laser power density and helped to make the MPA efficient. The beams meant to form interference were selected by an aperture array, which is placed between the two lenses. Negative photoresist SU-8 (Microlithography Chemical Corp.) was used as an initial material for the fabrication. The absorption spectrum of SU-8 indicates that one-photon absorption is negligible at an 800-nm wavelength. Consequently, it is expected that photopolymerization, if occurring, is due to a multiphoton reaction. The layer of SU-8 was spin-coated on a coverglass plate having a thickness of about 4 μm, and prebaked before exposure to fs pulses. The interference angles θair (the angle between the main optical axis and the other beams in air) applied in the experiments were measured to be 33.6°, 21.9°, and 10.8°.
(a)(b) Top view and oblique view SEM images of the structure fabricated by the four-beam interference of fs pulses, (c) Close-up view of rods in the structure fabricated by four-beam interference of fs pulses with an interference angle of 21.9°.
Femtosecond pulses from a Ti:sapphire regenerative amplifier (wavelength of 800 nm, pulse duration of 150 fs, repetition rate of 1 kHz) were used for experiments. By using this method, periodic structures were fabricated. Periodic structures fabricated with an interference angle of 33.6° are presented in Fig. 14. In this figure, (a) and (b) show SEM images of the same sample from different perspectives. The oblique view shown in (b) clearly demonstrates that the periodic structure consists of high-aspect-ratio rods. The height and diameter of the rods are about 4 μm and 0.6 μm, respectively; thus, an aspect ratio of about 7 was achieved. It should be noted that the height of the obtained structure is not limited by the coherent length of the pulse. A higher structure could be obtained if the stiffness of the material allowed the rods to withstand capillary forces during the development procedure.
Figure 14 (c) provides a close-up view of the rods fabricated with an interference angle at 21.9°. To obtain this image, the coverglass containing the fabricated structures was deliberately broken and a small fragment was observed. As seen, the rods are slightly bellows-shaped. Distinct ring-like features repeat periodically along each rod with a period about 0.3μm. This could be attributed as the result of interference between the incident and reflected beams at the resist–coverglass interface.
In conclusion, we have reviewed the fabrications of the one-dimensional and two-dimensional periodic microstructures on the surface or inside of materials by multiphoton absorption using a single shot of two or multiple interfered femtosecond laser pulses.
Firstly, we have introduced the fabrication of the microgratings by a single shot of two interfered femtosecond laser pulses. When two interfered pulses overlapped on the surface of the silica glass, not only did we get the ordinary grating whose periods accorded with the theoretic equation d=λ/[2sin(θ/2)], but also obtained the extraordinary grating whose period is a half of the ordinary grating. The formation of the modulation grating could be attributed to the higher-order modulation arising from second-harmonic generation (SHG) when the femtosecond laser pulse was incident to the surface of silica glass. The multiple layers of the microgratings have been fabricated in the different depths of the silica glass sample by a single shot of two interfered femtosecond laser pulses, and the results show that the fabricated gratings can be read out by one of the recorded beams very easily. The noble metal nanoparticles consisted microgratings have also been realized in silicate glasses by two interfered femtosecond laser pulses with the aid of heat treatment because the noble metal nanoparticles in silica glass can be precipitated after the irradiation of the femtosecond laser and the successive heat treatment. At the same time, the multiple gratings can also be realized on the surface of the silica glass samples by a single shot of two interfered femtosecond laser pulses with the aid of a mask, which is very significative for enhancing the processing efficiency of the fabricated microgratings.
Secondly, we have also introduced the fabrication of the 1-D or 2-D periodic microstructures by a single shot of multiple interfered femtosecond laser pulses. When a single shot of three coplanar interfered femtosecond laser pulses interfered with each other on the surface of the silica glass, M-shaped gratings can be formed and the morphologies of the M-shaped gratings can also be modulated by tuning the incident pulse energy. However, when a single shot of noncoplanar three or four pulses interfered with each other, two-dimensional periodic microstructure can be obtained, which distributed as a hexagonal lattice. Different morphologies of the induced structures such as microvoid, orbicular platform and nanotip, could be formed with the changes of the incident pulse energy. The fabrication of the 2D tetragonal lattice have also been fabricated in Negative photoresist SU-8 by four noncoplanar interfered pulses originating from the single pulse with the aid of the special DBS (diffractive beam splitter). Although the special DBS provided an easy way for realizing multiple beams interference, it also had some shortages, such as difficulty for fabricating microstructure with a smaller period, especially in the materials with big bandgap, such as silica glass.
This work was supported by the National Science Foundation of China (NSFC: 10904027; 61108018), the China Postdoctoral Science Foundation (AUGA41001348) and the Heilongjiang Province Postdoctoral Science Foundation (AUGA1100074), and development program for outstanding young teachers in Harbin Institute of Technology, HITQNJS. 2009. 033.
Answers regarding the value of a medical system can vary depending on various considerations and degrees of interest. Even when considering the universal values of human life and health, their implications are presumed to depend both on the sense of individual values and a country’s history, culture, national character, and surrounding socioeconomics [1, 2]. Meanwhile, if we discuss human dignity’s ethical and moral aspects, the fundamental values of health and life typically exhibit a consensus within the minimum necessary basic range. In other words, the value of the medical system can be considered a mechanism for stable supply (cultivation of a sense of security) that guarantees basic human rights. Given the socio-economic background, the significance of discussing the medical insurance systems of countries from this perspective has recently been increasing. Under these circumstances, the World Health Organization (WHO) has promoted universal health coverage (UHC).
UHC refers to universal access to all people for necessary healthcare services—irrespective of time, place, and their financial condition. UHC, a goal that the healthcare system must strive to achieve, includes basic health services: promotion, prevention, treatment, rehabilitation, and palliative care. This goal takes the civic perspective. Given this background, the understanding and contribution of all members of society (citizens) is essential to the realization of UHC. Its promotion requires a balance between the benefits and burdens at the citizen level. The aforementioned value trends were involved in discussing this balance. In other words, the choices and decisions of individuals and groups are influenced by values. However, issues related to equity and efficiency exist in allocating resources for public goods. The significance of applying value theory and market principles, although limited, has been discussed for a long time [3].
Therefore, the political dimension is also important when considering UHC progress. To promote UHC, some issues regarding evaluating the medical insurance system must be resolved. The increasing importance of socio-economic measures in medical insurance systems has attracted considerable attention. In general, the following three issues have been addressed: (1) The perspective through which the medical insurance system’s outcomes (goals and significance) must be discussed and evaluated. (2) The measurement and analysis of the impact of socio-economic factors on health insurance system outcomes. (3) Determining the operation of the medical insurance system (e.g., benefits and burdens, allocation of resources) based on the aforementioned issues. Each issue has a broad and complex context; thus, consistent effort is required.
The development of public medical resources, especially the financial investment system (national burden and insured burden), is indispensable for the sustainable operation of the medical system. Therefore, an analysis of the characteristics of each country’s political systems is required. As rational policy decision-making is imperative for discussing the financial burden, analytical tools such as those presented in this chapter are necessary. For example, in future studies, a cost-effectiveness analysis (CEA) could be conducted. Additionally, adopting a longitudinal research design (panel data analysis) would make it possible to account for the effects of fluctuations in external factors—such as the real economy—with high accuracy. For example, a report suggests that it is important to optimize resource allocation from the perspective of public interest rather than simply increasing the medical expenses per capita to develop the medical insurance system [4].
Based on the above, harmonizing the public and private sectors is a theme in healthcare insurance systems. This coincides with harmonizing the benefits and burdens of healthcare policy between individuals and society. This requires a macroeconomic analysis of the relationship between health sector outcomes and socio-economic factors. Therefore, this approach also involves financial aspect and discusses the relationship between the real economy and public interest activities. Regarding healthcare services, there is a lot of discussion about payment formulas and price levels in the relationship between stakeholders (economic payers, providers, and service recipients) [5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16]. In other words, there are themes related to the proper allocation of social security funds and the improvement of inefficiencies in the public market. Therefore, a microanalysis is essential in the discussion of healthcare insurance systems. From this perspective, utility theory and welfare economics are applied to elucidate the mechanisms of price formation and treatment selection behavior.
In particular, these themes are becoming more important in the quasi-public medical market, such as Japan’s universal health insurance system, medical resources consisting of social premiums, general taxes (including subsidies), and patient out-of-pocket expenses. For example, rising drug prices and procedure fees have a structure that rebounds from social and individual burdens. Therefore, the significance of comprehensively discussing phenomena and issues that straddle both macro- and micro-aspects has been emphasized (Figure 1). For example, high expectations for cost-effectiveness evidence can be applied to macro- and micro-issues to ensure the sustainability of the system and the appropriateness of resource allocation. From the above, three closely-related perspectives will be discussed: an examination of UHC considering socio-economic factors, examination of the significance of citizens’ value in resource allocation, and examination of price formation considering patients’ economic burden.
Three closely related perspectives are examined: An examination of UHC considering socio-economic factors, the significance of citizens’ value in resource allocation, and price formation considering the economic burden of patients. Note: UHC, universal health coverage.
This chapter explains the concept of the approach required to address the aforementioned issues and introduces examples of related research reports as a guidepost for discussions in the areas concerned. In the first section, the socio-economic factors that affect UHC are examined, and examples of quantitatively evaluating these relationships and their analysis results are provided. Subsequently, the concepts of medical value and methodology, which are indispensable to the ideal development of the medical insurance system, are summarized. Research cases related to the significance of lifesaving and drug discovery are introduced, considering the possibility of allocating public resources. In the final section, the concept of price (fee, charge) formation, which also considers medical value, is organized based on the characteristics of economics and medicine. For example, a report that analyzes the mechanism of price levels, focusing on Japanese private practice (out-of-pocket), is introduced.
Sustainable Development Goal (SDG) 3 comprises 13 targets related to “health and welfare for all.” The other 16 goals were either related—or indirectly contributed—to health. The SDGs aim to “leave no one behind” and are international objectives applicable to developing and advanced countries. UHC is a concept that includes 1) protection from financial risks for all, 2) access to quality primary health services, and 3) access to essential medicines and effective, high-quality, and inexpensive vaccines. Target 3.8 SDG 3, which involves achieving UHC and health improvement worldwide, is considered the most crucial task of the WHO [17].
The measurement approaches and definitions of the UHC index evolved between 2015 and 2019, and the index is now used in every global monitoring report [18]. UHC progress between regions and countries can be compared. Additionally, the UHC service coverage index (SCI) has been calculated as a single number (i.e., score) since the late 2010s, thereby improving comparability between nations. Although the performance of different countries can now be compared, global monitoring alone is insufficient to guide policymaking [19]. Therefore, each country should be encouraged to develop a country-specific global framework. The relationship between the environmental factors surrounding medical care and progress toward UHC should be analyzed to achieve this.
Healthcare systems generally help improve clinical outcomes by increasing public financial investment [20, 21]. Meanwhile, declining birth rates, aging populations, and the maturation of medical systems generally tend to reduce the baseline performance of medical systems. Some reports mention that unemployment and poverty, which are distant causes of catastrophic health costs, are factors that reduce service coverage index levels [22]. Therefore, there is room for countermeasures, including population policies and economic measures. For example, future economic growth strategies could include the promotion of healthcare and life sciences industries. Improvements in health care programs include disease prevention and medical insurance policies.
Problems regarding medical financial systems constitute a significant challenge to achieving UHC. According to the WHO, a healthcare financial system that eliminates the financial constraints of access to health services is crucial [23, 24]. Several previous studies have suggested that UHC is more likely to be achieved when patients’ out-of-pocket medical costs are low [25]. As rational policy decision-making is imperative for discussing the financial burden, analytical aspects, such as UHC and socio-economic factor relationships, are necessary. For example, CEA, a performance analysis of medical functions, is the most common approach for assessing the health benefits for each spent or the cost for each additional health unit. CEA is a tool used to enhance the sustainability of medical systems.
This section introduces an example of the relationship between SCI and major socio-economic indicators to establish UHC levels and economic factors [25]. This study used SCI as a proxy for progress toward UHC in 11 Asian countries. A fixed-effects regression model was employed to analyze panel data from 2015 to 2017, and to explain the interrelationship between the SCI and major socio-economic indicators (health expenditure, unemployment, etc.) Performance analysis (to determine the ratio of the achieved SCI level to gross domestic product or health expenditure displacement) was also conducted. This analysis examines the balance between the degree of achievement related to UHC and a country’s economic level.
The gross domestic product (GDP) and SCI had a significant positive correlation (Spearman’s rank correlation coefficient [Rs] = 0.716, p < 0.01). Health expenditure and SCI were significantly and positively correlated (Rs = 0.743, p < 0.01). When both GDP and SCI indicators were transformed using logarithms, the abovementioned trend did not change significantly (Rs = 0.731, p < 0.01; Figure 2). The results of the panel data analysis showed that GDP per capita significantly contributed to SCI (standardized partial regression coefficient, 1.6129; partial regression coefficient, 0.0049; 95% Confidence interval [CI], 0.0025–0.0074; Table 1). The total population, governmental health expenditure, unemployment, and poverty rates were statistically significant, whereas health expenditure was not significant. The unemployment and poverty rates show a negative trend, and the entire model is statistically significant (R2 = 0.991, F-test: p < 0.001). The ROC curve for health expenditure per GDP for SCI showed a cutoff of 3.7% (p < 0.01) for the Youden index and 4.9% (p < 0.01) for the shortest distance (AUC = 0.8125, 95% CI: 0.6350–0.9899, p < 0.05; Figure 3).
Relationship between economic level (GDP) and SCI (logarithmic transformation, 2017). Note: UHC, universal health coverage; SCI, service coverage index [
UHC index of service coverage (SCI) | Partial regression coefficient | Standardized partial regression coefficient | SE | p-value | 95% CI |
---|---|---|---|---|---|
Population (total: million people) | 0.0049 | 0.1921 | 0.0012 | 0.0001 | 0.0025–0.0074 |
GDP per capita (current USD) | 0.0017 | 1.6129 | 0.0002 | < 0.001 | 0.0013–0.0021 |
Health expenditure (% of GDP) | 2.3481 | 0.4116 | 1.5748 | 0.136 | −0.7386–5.4347 |
Government health expenditures (% of general government expenditures) | 1.4511 | 0.6575 | 0.2804 | < 0.001 | 0.9015–2.0006 |
Unemployment rate (%: ratio of unemployed persons) | −1.4764 | −0.2253 | 0.7105 | 0.0377 | −2.8689–0.0838 |
Poverty rate (%: poverty gap) | −1.6736 | −0.2303 | 0.4674 | 0.0003 | −2.5897–0.7575 |
Model: R2 = 0.991, F test: p < 0.001 |
Panel data analysis of the impact of economic level (GDP, health expenditure, unemployment, and poverty) on SCI.
Note: GDP, gross domestic product; UHC, universal health coverage; SCI, service coverage index; SE, standard error; CI, confidence interval [21].
ROC curve of health expenditure (per GDP: %) for SCI (criterion: Score 70) [
From the results of the performance analysis after the logarithmic transformation of each index, South Korea (high-income country: HIC) scored the lowest (GDP: 0.12 SCI score/USD per capita, health expenditure: 0.07 SCI score/USD per capita; Figure 4), followed by Vietnam (lower-middle-income country: LMIC) and India (LMIC). Japan’s (HIC) performance was moderate, while Indonesia (UMIC), Thailand (UMIC), and Cambodia (LMIC) had relatively high performance. The Philippines (LMIC) had the highest performance (GDP: 1.84 SCI score/USD per capita, health expenditure: 1.04 SCI score/USD per capita). Myanmar (LMIC) was marked as the “dominant quadrant.” The more effective but less expensive quadrant exhibited the best performance in the cost-effectiveness analysis. When the relationship between the proportion of the population aged 65 and above was organized without logarithmic conversion, the SCI score increased with age (Rs = 0.779, p < 0.01), and the performance value decreased (Rs = − 0.830, p < 0.01; Figure 5).
Performance status by country (broad cost-effectiveness analysis based on displacement from 2015 to 2017). Note: SCI, service coverage index. *1: Dominant is positioned in a more cost-effective dimension with increasing outcomes (SCI) even if the economy (GDP) declines. *2: Performance was a cost-effectiveness analysis (difference in outcome “SCI” ÷ difference in the economy “GDP”; displacement from 2015 to 2017). Both indices were logarithmically transformed to consider the elasticity [
Trends in SCI and performance (economic level: GDP) with respect to the aging rate (percentage of the population aged 65 years and above). Note: UHC, universal health coverage; SCI, service coverage index. (†) Myanmar has a different quadrant (dimension) because it is “dominant” [
Each of the four SCI components had a different level of achievement (Figure 6). LMICs were most countries with SCI levels of 60 or below (i.e., Bangladesh, India, Indonesia, and Cambodia), where “infectious diseases” and “service capacity and access” were more widely dispersed. This was compared to the group of countries with SCIs of more than 80 (i.e., South Korea, Japan, Thailand, and China), HIC, and UMIC. Multiple regression analysis used SCI’s annual rate of change as the objective variable and SCI components as the explanatory variable. The results indicate that “service capacity and access” significantly contributed to the SCI level (standardized partial regression coefficient, 0.9209; partial regression coefficient, 0.3581; 95% CI, 0.3142–0.4019). Furthermore, when the GDP per capita and “service capacity and access” values of each country were relatively arranged, with Japan as the standard, a positive correlation was observed between the two indicators (i.e., single correlation: Rs = 0.901, p < 0.01) (Figure A1).
Distribution composition of SCI components according to SCI level (≥ 60 and ≥ 80). Note: SCI, service coverage index [
The present study used SCI as a proxy for the progress of UHC. Currently available service coverage metrics focused on infectious diseases and reproductive, neonatal, maternal, and child health [26]. In this study, the indicators for SCI-related data (Figure A2) were “reproductive, maternal, newborn and child health,” “infectious diseases,” “noncommunicable diseases,” and “service capacity and access.” In addition, the country-by-country socio-economic indicators included “total population,” “population aged 65 and above,” “gross domestic product (GDP) per capita,” “health expenditure per GDP/per capita,” “government health expenditures,” “unemployment rate,” and “poverty rate.” All data were converted into a panel from 2015 to 2017; SCI-related and socio-economic data were also compiled [27, 28, 29].
According to the analysis results derived by applying these data, UHC progress tends to increase as the share of the healthcare domain in government spending increases. Future studies on UHC development measures are important to discuss the appropriate form of resource allocation (public finance) according to sustainability-based productivity and efficiency or value evaluation (national consensus). Based on the statistical analysis results, some cases exist wherein SCI achievement levels differ even among countries at the same economic level. Furthermore, SCI improvement is small, even in countries with high economic investment levels. Exploring these factors and considering improvement measures are assumed to promote UHC progress. This study examined the influences of the maturity of the medical system as an additional country-specific factor (rather than the social system, national character, and culture).
The results showed that when aging and health expenditure exceed a certain level, UHC performance decreases as a country’s need to raise its goal increases. Additionally, the weight of “service capacity and access” to SCI was considerable. This secondary index, which embodies the environment of the healthcare system, can be considered a surrogate index that predicts the maturity of social and medical care. The considerable impact of these factors on UHC implies that stable development cannot be expected simply by expanding the expenditure scale due to the mechanisms related to economic conditions. As a result, policymakers must implement countermeasures based on indicators that can estimate the economic status of the UHC approach, such as its cost-effectiveness.
CEA is often applied to medical-economic evaluations, such as high-priced medicines and health programs, but can also be applied to macro issues, such as medical systems [30]. Cost-effectiveness is an instrument widely used in Western health systems. The instrument provides the information needed to reach a consensus among stakeholders in allocating medical resources and setting medical prices. As UHC progress requires country-specific efforts, as discussed in the introduction, estimating the coefficients that define each country’s UHC progress and socio-economic status is also necessary. Hence, a country-specific performance analysis (CEA: country-specific coefficient calculations) was conducted. In the present study, CEA was performed using economic level as a cost index and SCI level as an effective index.
This approach suggests that regardless of the maturity of the system or the size of the economy, the status of UHC activities in each country can be evaluated based on the displacement of economic and SCI levels achieved.
This section summarizes the conditions and mechanisms of the link between value and price discussion in a medical system.
In a private economy, where the market principle works, goods (and services) are demanded and supplied in the market based on people’s decision-making (free choice and action) depending on changes in price levels. If the market works well, supply and demand will be balanced, and various goods will be properly distributed. The relationship between benefits and burdens in this market is easy to explain. Meanwhile, in a public economy, where the government is the main operator, the market principle works in a limited way. Taxes that enforce the burden are a receiver of supply costs for the demand of goods.
Therefore, public needs and expenditures (including reallocation) are generally determined by the government’s judgment. However, price levels in the public economy are often formed by costs (e.g., size of spending budget), which are both inefficient and inconsistent with market utility (i.e., consumer satisfaction). Additionally, the allocation of public resources may deviate from the balance between supply and demand, and inequity among participants within a group may be promoted. Thus, issues related to Use-value, Marginal utility, and Pareto optimization become apparent in the public economy [31, 32].
Subsequently, the concept of verifying the economic appropriateness of the market function and product price (among others) arises by balancing the number of resources consumed and the results obtained (e.g., cost-effectiveness and performance) [2]. As an example of its widespread use, considering large-scale public investments (e.g., the construction of dams and bridges), the desirability of the project’s implementation is evaluated based on its cost-effectiveness. Additionally, in the private economy, where technological innovation is active, and consumers have numerous choices, the concept of cost-effectiveness is used more actively to incorporate activities and stimulate product appeal. Consequently, the basic and broad concept of cost-effectiveness has developed in social policy decision-making and resource management fields. Its know-how has been cultivated in contract society and management activities and used in social consensus-building and decision-making.
Meanwhile, the provision of medical services is characterized by information asymmetry and restrictions on opportunity costs (options) against the background of health and life. Therefore, healthcare markets differ from common markets that exhibit typical demand and supply; this market has three parties (citizens, insurance, and providers) and faces asymmetric information that creates several market problems (i.e., common equilibrium market laws do not apply), including problems in defining prices. Although this is inherently unfair (bias) in the health sector from the perspective of citizens’ financial burden, the system is based on medical needs such that the needs of the patient, regardless of the outcomes, receive the same medical care. Since such a tendency threatens the system’s sustainability, there have been attempts to improve it as much as possible by utilizing cost-effectiveness and utility theory.
By their very nature, public goods are non-competitive; therefore, the role of price tends to be smaller. Medical care has restrictions on individual choice. However, CEA (including cost-utility analysis [CUA]) is widely used to evaluate medical technology in high-income countries, and prices are determined according to this evaluation. Recently, pricing has become more common with evidence-based or value-based approaches. In this method, a consumer’s natural internal decision-making regarding consumption behavior is externally substituted by other stakeholders under certain conditions (typically advocating the maximization of group benefits) for a certain group or system based on the law of equal marginal utility and expected utility theory. These methods will be considered along with the uncertainty of outcomes and limited rationality of human beings.
The medical systems of many countries have historically operated as part of the social security system, as they gather high public interest from the necessity for all people. Further, against the background of stable supply, the pricing of medical services has often been based on costs. As described in the previous section, numerous developed countries face structural issues, such as declining birth rates, aging populations, and rising costs of medical services; thus, verification of price levels has become an urgent concern [25]. Therefore, the need to build a social consensus on the economic burden of the value of medical services has been increasing, and the verification of price levels while considering cost-effectiveness has further expanded [33]. Against this background, discussions on value evaluation and price levels in the medical field are being conducted using various approaches to consider cost-effectiveness.
Utility refers to the degree of subjective satisfaction or demand fulfillment that each consumer obtains when consuming a certain good or service and is considered a fundamental concept in economics [34]. When interpreted broadly, human economic activities and all human behaviors (including the selection of medical services) aim to maximize the utility to be acquired as the background. Thus, this concept can explain the background of stakeholder behavior changes (e.g., decisions and choices) in the field of health care [35]. Furthermore, a method supported by varied theories related to utility was assumed as an approach to value evaluation.
In summary, “value” is regarded as the meaning of the existence (usefulness or significance in a narrow sense) of an object regardless of whether it is “tangible or intangible.” For example, in the public sector, meaning is often organized using exchange value and use-value. A value is diverse and difficult to quantify in general; however, it should be explained to the parties concerned (Figure 7) [36] when discussing it as part of a social system. This perspective is even more important for the effective utilization (fair distribution) of public properties. Aspects related to life and health should first be discussed from the perspective of “use-value” in developing society. Furthermore, medical care is expected to be provided to everyone at a fairly low cost (public aspect).
The conception of value assessment in the quasi-public healthcare system: The balance of the valuation of technical innovations and the guarantee that all patients have access. The public medical marketplace requires a system that considers both use and exchange values [
Therefore, several countries worldwide have more or less developed the medical field as a public system, following the lead of the 1978 Alma Ata Declaration. Specifically, Japan’s universal health insurance system is assumed to have experienced this trend (see Figure 8). However, highly specialized professionals and therapeutic materials require large investments in developing medical resources, and their supply is restricted. Therefore, to operate and develop medical care as a social system—considering the “exchange value” content that accompanies scarcity and building a system that incorporates certain market principles (economic aspect)—are crucial [2]. This perspective is also important in discussing consistency within the real economy.
Significance and key characteristics of value measurement in the public economy (decision-making and resource allocation) [
Thus, in a quasi-public healthcare market such as Japan, it is desirable to provide mature and widespread medical care at low-cost while guaranteeing a high economic level for innovative (or effective) medical care and specialized resources. Moreover, a system that balances the use and exchange of values is necessary. As previously mentioned, assessing value in the medical field involves various restrictions. Value evaluation can be performed in several ways, which are inadequate for consistency with the real economy or developed as a theory of price setting. The approach to value evaluation that contributes to the discussion of economic activities and official prices in the healthcare system is as follows:
Generally, in microeconomics, prices converge based on supply and demand equilibrium with the background of utility theory, and efficiency is thus maximized. Incorporating herein the perspective of equity (well-being), public interest value is discussed based on the balance between patient utility value (preference, willingness to pay) and medical finance (income reallocation, finance balance) (Figure 9). The balance between increasing utility and cost per health program unit while weaving individuals and society is thus considered. As a result, if utility is maximized in a certain budget range, the higher performance increases the utility in a total of the entire population, and the stakeholders’ “value” increases. Compared to the conceptual discussion of value, it is relatively possible to discuss consistency with a real economy or a general value; hence, it is considered suitable for examining the medical price of the public sector.
Concept of value evaluation of health care based on utility theory and cost-effectiveness considering welfare economics.
The value of medical services can be indirectly evaluated in the public sector by applying the marginal utility theory and scales based on preferences while considering different conditions and objectives from those in the private sector [37]. Incidentally, in the medical field, a method for measuring and analyzing patient utility values as a type of health-related quality of life has been developed. The application of this concept to CEA is CUA, which is a type of CEA. Based on the above, the medical value is calculated as “health recovery (patient outcomes such as utility)/resource consumption (direct medical cost) ⇒ medical performance = medical, economic value” [38] (Figure 10). A related concrete methodology is cost-effectiveness analysis, which considers health programs’ medical and economic position.
Concept of economic performance: One of the methods used to discuss the economic value of healthcare. “Value” in social activities is determined by the balance between capital investment and its returns. If a certain amount of money is paid to use a certain service (function), its value is determined by performance, equal to the amount of service (function) divided by the cost. For the consumption of one budget item, the greater the result, the higher is the value. The amount in terms of “restoration of health” is used as an index of “function” in the medical field [
This explains the socio-economic significance of the medical services provided by balancing public costs and earned utility in the medical market. It is believed that the higher the performance, the greater the utility (clinical outcomes for patients) as part of the value of the budget range.
This section introduces reports that discuss the socio-economic significance of the spread of lifesaving medical devices and the research and development (R&D) of expensive pharmaceuticals (at the time of 2010).
First, a case of microeconomic valorization of end-stage renal failure is discussed [39]. With the progression of renal impairment in patients with chronic kidney disease, the dysregulation of electrolyte and water metabolism and retention of uremic toxins can significantly impact health status and even threaten life [40]. Treatment with hemodialysis (HD) should target maintaining the amount and composition of body fluids within the normal range. The study subjects were aged >20 years and had received HD for at least 6 months. HD patients were prospectively observed for 36 months, and patient utility was assessed based on the EQ-5D, from which quality-adjusted life years (QALYs) were estimated. Medical costs were calculated based on the medical service fees. Cost-effectiveness, defined as the incremental cost-utility ratio (ICUR), was analyzed socially. A total of 29 patients (mean age; 59.9 ± 13.1 years) undergoing 437 dialysis sessions were analyzed.
Utility-based EQ-5D score was 0.75 ± 0.21, and the estimated total medical cost for 1 year of maintenance HD (MHD) treatment was 45,200 ± 8800 USD. On average, the ICUR was 68,800 ± 44,700 USD/QALY (Figure 11). When comparing the ICUR based on the causes of kidney failure, the value for diabetic nephropathy was higher than that for glomerulonephritis (81,700 ± 62,800 vs. 68,200 ± 40,700). The ICUR after 36 months of observation increased mainly in patients below 65 years of age (all P < 0.05; <65, P < 0.01; ≥ 65, not significant) (Figure 12). MHD could improve the socio-economic status of older-adult patients with end-stage kidney disease; however, the ICUR for diabetic nephropathy was higher than that for glomerulonephritis (Table 2). However, the ICUR does not deteriorate in older-adult patients. Therefore, measures to prevent malnutrition and establish the optimum time per session and frequency of dialysis (i.e., optimal dialysis volume) are necessary to further improve MHD’s cost-effectiveness.
Utility values (EQ-5D score) during the first 4 weeks of observation and the 36th week. Four-week interval after the classification of primary diseases for end-stage kidney disease (glomerulonephritis, diabetes mellitus, and the whole) [
Change in cost-effectiveness (ICUR) between the first 4 weeks of observation and the 36th four-week interval. *p < 0.05, **p < 0.01 [
Parameter | All Subjects | Glomerulonephritis | Diabetic nephropathy | Others | ||
---|---|---|---|---|---|---|
Utility(QALYs) | ||||||
Mean ± SD | 0.75 ± 0.21 | 0.73 ± 0.17 | 0.68 ± 0.23 | 0.83 ± 0.22 | ||
Median | 0.73 | 0.71 | 0.60 | 1.00 | ||
* | ** | ** | ||||
Mean ± SD | 45,200 ± 8800 | 45,300 ± 8800 | 51,100 ± 10,700 | 41,100 ± 4100 | ||
Median | 43,300 | 44,100 | 43,500 | 41,900 | ||
** | ** | ** | ||||
Mean ± SD | 68,800 ± 44,700 | 68,200 ± 40,700 | 81,700 ± 52,800 | 54,600 ± 27,400 | ||
Median | 58,700 | 60,900 | 81,100 | 44,400 | ||
** | ** | ** | ||||
Dialysis time (hour per intervention) | ||||||
Mean ± SD | 4.35 ± 0.50 | 4.19 ± 0.39 | 4.08 ± 0.43 | |||
95%CI(two-sample population mean) | 0.16(0.01.0.28) | 0.11(-0.01.0.23) 0.27(0.16, 0.37) | ||||
Cr(mg/dL) | ||||||
Mean ± SD | 9.93 ± 2.11 | 9.47 ± 2.39 | 10.97 ± 3.24 | |||
95%CI(two-sample population mean) | 0.45(-0.78, 1.70) | 1.50(-0.09, 3.09) 1.04(-0.29, 2.38) | ||||
BUN(mg/dL) | ||||||
Mean ± SD | 67.09 ± 15.62 | 69.43 ± 16.92 | 72.43 ± 12.38 | |||
95%CI(two-sample population mean) | 2.34(-4.87, 9.56) | 2.99(-4.20, 10.20) 5.34(0.02, 10.65) | ||||
Age(years) | ||||||
Mean ± SD | 63.59 ± 12.30 | 63.78 ± 4.27 | 51.78 ± 14.08 | |||
95%CI(two-sample population mean) | 0.18(-1.88, 2.26) | 12.00(9.19, 14.81) 11.81(8.63, 14.99) |
Cost-effectiveness by utility and cost in patients on maintenance hemodialysis (MHD).
*p<0.05. **p<0.01. The data source for this analysis was the mean value over 4 weeks in 2011. BUN. blood urea nitrogen: CI. Confidence interval: Cr. creatinine: SD. Standard deviation: QALYs. Quality-adjusted life years. These values were analyzed by distinguishing between the primary disease of end-stage kidney disease (ESKD), glomerulonephritis, diabetic nephropathy, and others during the first 4 weeks of observation [39].
The present findings may contribute to the reexamination of the socio-economic value of MHD therapy, which is a lifesaving medical treatment.
Subsequently, a case of socio-economic valuation of a (then) new drug for the refractory nephrotic syndrome was discussed [41]. Nephrotic syndrome is the generic name for the pathological conditions associated with proteinuria (≥3.5 g/day), hypoproteinemia, and generalized edema. The disorder is further classified as a primary nephrotic syndrome (caused by primary glomerular disease) or secondary nephrotic syndrome (caused by systemic disorders). The syndrome rapidly improves with steroid (e.g., prednisolone) and immunosuppressant (e.g., cyclosporine) treatment. Refractory cases (frequent relapse type, steroid dependence, or steroid resistance) may also occur, requiring steroid therapy for prolonged periods, for which side effects become a major issue. Therefore, there is a need for novel medical strategies to suppress relapse while reducing reliance on steroids. The regimen has not been clinically verified regarding the use of rituximab in patients with steroid-dependent nephrotic syndrome and frequently relapsing nephrotic syndrome. Still, there is a lack of evidence in health economics [42].
Therefore, we conducted a prospective clinical study of 30 patients before (with steroids and immunosuppressants) and after introducing rituximab therapy (Figure A3). Relapse rates and total medical expenses were selected as the primary endpoints for treatment effectiveness and treatment costs, respectively. As a secondary endpoint, cost-effectiveness was compared before and after rituximab administration in relation to previous pharmacotherapy. The observation period was 24 months before and after rituximab initiation. The authors demonstrated a statistically significant improvement in the relapse rate, from a mean of 4.30 events before administration to a mean of 0.27 events after administration. Furthermore, a significantly better prognosis emerged in the cumulative avoidance of relapse rate by Kaplan–Meier analysis (p < 0.01) (Figure 13). Finally, the total medical costs decreased from 2923 USD to 1280 USD per month, and pre-post cost-effectiveness was confirmed to be dominant (Figure 14). Thus, treatment with rituximab may be superior to previous pharmacological treatments from a health economics perspective (Table 3). Although this study did not directly observe patient utility, the excellent results in recurrence rates suggest an improvement in HRQOL.
Kaplan–Meier curves of the cumulative avoidance rate of the first relapse [
Mutual relationship between urinary protein levels and total medical cost (before and after rituximab therapy) [
Items | Pre-administration | Post-administration | Difference (after-before) |
Medical cost difference (points/24 months) | 725,403 | 317,707 | -407,696 |
(USD/24 months) | (70,155) | (30,726) | (-39,429) |
Relapse difference (times/24 months) | 4.30 | 0.27 | -4.03 |
Pre-post CEA (points/24 months/times) | 101,082 | ||
(USD/24 months/times) | (9776) | ||
Reference: pre-post CEA with a case in which the analysis was restricted to 17 months (points/17 months/times) | 50,982 | ||
(USD/17 months/times) | (4931) | ||
Items | Pre-administration | Post-administration | Difference (after-before) |
Medical cost difference (points/24 months) | 725,403 | 401,539 | -323,864 |
(USD/24 months) | (70,155) | (38,833) | (-31,321) |
Number of relapses (times/24 months) | 4.30 | 0.27 | -4.03 |
Pre-post CEA (points/24 months/times) | 80,297 | ||
(USD/24 months/times) | (7766) | ||
Reference: pre-post CEA with a case in which the analysis was restricted to 17 months (points/17 months /times) | 29,445 | ||
(USD/17 months/times) | (2848) |
Medical economics analysis (pre-post-CEA) accounting for the medical costs of rituximab.
The analysis has been corrected for the number of months. Pre-post CEA was calculated as [medical cost (post-pre)/medical effectiveness (post-pre)] (suppression amount for medical costs accumulated over 24 months per one-time reduction[avoid] in relapses). Expressed as points per 24 months per time. Analyzing the cost-effectiveness (the ratio of total medical costs and a number of relapses, after correction for the number of months) before and after rituximab therapy revealed that cost-effectiveness improved in medical, economic terms. This was 317,707 points (30,726 USD) per 24 months (0.27 times) after rituximab therapy compared with 725,403 points (70,155 USD) per 24 months (4.30 times) before therapy [41].
As this study indicates the superior cost-effectiveness of rituximab against refractory nephrotic syndrome, health economics is expected to be actively applied to the valuation of technical innovations such as drug discovery.
The discussion of value covers the whole range of activities related to the health and welfare field, such as examinations and diagnoses provided by medical facilities, surgery, and hospitalization, as well as medication, therapeutic materials, and care provided by caregivers. Prices (i.e., official prices in Japan) are attached to several services. Professionals who typically work in clinical or long-term care sites may not be very aware of these prices. However, the financial resources for the operation of medical and long-term care facilities are based on the price of services provided to patients/family members and long-term care recipients, who are the so-called beneficiaries. The medical institution charges to insurer for various services provided to the assured patient, which become the source of salary payments and reinvestment for the parties concerned. Therefore, if the price, value to be generated, and amount of resources consumed are not well balanced, the motivation for the employment of professionals and profitability assumedly decreases, thus making sustainable facility management difficult.
Consequently, the supply of medical and long-term care will decline, which is a significant problem for residents, including patients and their families [43, 44, 45]. Therefore, the price levels at which service recipients and providers are mutually satisfied (or convinced) should be discussed. However, determining the characteristics and effects of the target market is necessary to discuss the appropriateness of the price, considering the theory related to human choice and behavior (outlined in the previous section). In particular, as the field of health and welfare has service characteristics that are different from those in other fields, it is necessary to consider and interpret the mechanism of the market. Against this background, this section explains the basic price and its calculation methods.
The behavior and motivation of market economic agents and the pricing mechanism for goods and services, including resource allocation and income distribution, should be considered for price optimization. Overall, the general economic approach is limited because of various uncertainties related to highly specialized technologies in medical science. Thus, examining price settings in the medical field is generally difficult because of the complex involvement of various factors. A price-setting approach in medical treatment can be divided into two major categories: “market-based” and “input-based” [46]. The “market-based” approach determines the price level by considering the actual market price of medical treatment, while the “input-based” approach is based on the consumption of goods and services. Generally, prices are presumed to have been formed in the public medical market using these approaches in countries with a mature medical system.
Approaches to explain the public price of individual medical technologies (services) have also been discussed. For example, from the standpoint of a medical provider (supply approach), “technical difficulty” and “medical cost” are often selected from the viewpoint of quality evaluation and business management. Furthermore, for the payer (or beneficiary), the methods of “patient outcome,” “economic performance,” and “willingness to pay” are often selected from the perspective of market and value evaluation (Figure 15) [48, 49, 50]. Additionally, cases exist in which certain preconditions are set to use these indicators. For example, in Japan’s universal health insurance system, most prices charged to public insurers by medical institutions are centered on direct medical costs, based on the consumption of medical resources—considering their clinical usefulness and hospital operability. Technical fees (e.g., surgery fees), influenced by doctors’ specialties, are considered technical difficulties. Furthermore, overseas (developed countries) market prices are referred to when determining the public prices for pharmaceutical resources and medical devices.
Theory of the price-setting approach (in general and within the range of this examination) [
As the socio-economic environment surrounding the medical system becomes more severe, even public prices that follow the theory of the public economy are expected to play a role in improving the system’s performance and increasing its sustainability. In other words, verifying the structure of price formation and the appropriateness of its level has become a major concern for medical stakeholders. Based on this, an analysis of factors that affect prices is also expected. However, when developing official price research in the medical field, the following must be noted: There are not enough research reports to study the analytical model required for factor analysis. This condition is especially true in Japan. In addition, the formation of official prices involves various subsidy programs (politics), and thus, the analytical approach becomes too complicated. Therefore, in this chapter, as an initial study on medical prices, we introduce a survey on price differences between Japan and overseas and price factors in the private market.
This study examines the mechanism of market price reference and the influence of the real economy (citizens’ economic burden) on the public price, contributing to the arrangement of public price discussions in the future.
This section presents a method for setting the price level based on the analysis of medical expenses of Japanese medical institutions for foreign visitors (FVs). Furthermore, international comparisons of price levels for Japanese tourists (patients) in foreign countries have been conducted previously [47]. This section elucidates the “market-based” and “input-based” approaches discussed in 4.1, and discusses the “foreign price reference system,” which is part of the setting of public prices in Japan. In recent years, the supply of medical services centered on pharmaceutical products has been based on global R&D, manufacturing, and sales systems. In addition, some patient groups also exhibit cross-border consultation behaviors. In other words, it is inferred that discussions with a view to the globalization of medical care are indispensable for the progress of UHC, even if they are indirect.
The costs were analyzed based on socio-economic ranges in this calculation, considering clinical characteristics and economic activities. The costs related to general medical care and public investment in hospital management and healthcare infrastructure through the insurance system and various taxation systems that support Japan’s medical system are also considered. For example, social insurance burdens (e.g., insurance contributions and subsidies, such as operational grants to medical institutions) and additional expenses for FVs (e.g., interpretation, coordinator, equipment, and risk management costs) were used as calculation items.
Three medical institutions with more than 400 beds were chosen as target facilities, and their locations (urban or rural) were considered. Additional factors (such as the occupancy and profit rate of each facility) were considered in the calculation. Data collection involved medical practice and medical institution management surveys. The medical practice survey used time study (i.e., occupation time of medical staff and institutional equipment) and medical records (i.e., electronic and management ledgers): Some were self-reported alternatives based on their professional experience. The medical institution management survey collected financial statements (profit and loss balance sheets), number of patients and medical treatments, number of staff and equipment, unit purchase price, and the area of each department.
The medical expenses for FVs were broadly divided into “additional expenses of foreign medical treatment” and “increased expenses of regular medical treatment.” The following definitions for additional and increased expenses were applied: additional expenses for new and additional services (e.g., interpretation and transportation) for non-locally insured patients. The increased expenses for medical services were similarly offered to the locally-insured patients. However, for non-locally-insured patients, the unit price and quantity increased (e.g., consultation hours and staff). Profit was included in this calculation as a necessary resource for reinvestment by medical institutions to realize sustainable management while appropriately responding to the medical needs of FVs. However, when determining profit margins, the historical average of each institution was adopted to avoid the distortion of price levels and the expensive economic burden on FVs owing to excessive profits. The profits gained from FVs were essentially the same as those from Japanese patients.
Compared with the medical expenses (point system) of Japanese patients, those for FVs were 1.31 times (1 point 0.12 dollars) higher for pharyngitis, 1.56 times (1 point 0.14 dollars) higher for urticaria with allergies, 2.21 times (1 point 0.20 dollars) higher for hemorrhagic cystitis, 3.66 times (1 point 0.34 dollars) higher for in patients with severe pneumonia, 1.22 times (1 point 0.11 dollars) higher for general appendicitis, and 2.92 times (1 point 0.27 dollars) higher for endoscopic cholangitis treatment (Figure 16). Moreover, the operating expense for trochanteric fractures of the femur was 3.59 times (1 point 0.33 dollars) higher. Figure 17 shows the amount billed when providing medical treatment to Japanese overseas travelers (overseas FVs) in each country. The survey indicated that although the total number of patients was 18 (one in each country, except for the USA, Australia, Italy, and China), the actual medical payment was approximately USD 20.32–158.75/bill (medical expenditures for medical examination and drug cost) in 12 countries. The highest price was in the USA, at USD 158.75/bill (medical fees may be partially unknown), followed by Austria with USD 79.38 (purchasing power parity 86.28)/bill and Belgium with USD 73.93 (purchasing power parity 73.93)/bill. In summary, including additional research, the medical expenses for FV patients were 1.22–3.66 times higher than those for Japanese patients, 1.31–2.21 times higher for outpatients (pharyngitis, urticaria, and cystitis), and 1.22–3.66 times higher for inpatients (e.g., with severe pneumonia, appendicitis, cholangitis, and femoral fractures).
Calculation of price levels for foreign visitors (seven diseases) [
International comparison of medical expenses (pharyngitis and outpatients) [
The concept of factors that form the parturition price operated by the private medical care system (out-of-pocket) and the actual situation of the difference in price level due to regional characteristics [51] is introduced. This approach spans both “market-based” and “input-based” approaches, as discussed in Section 4.1. For the sustainable operation of the medical system, it is important to consider the stability of hospital management and the financial burden on citizens. In other words, it is presumed that discussions that consider the relationship between economic factors and medical treatment behavior are indispensable for the progress of UHC. This study has the advantage of developing purely causal inferences on that subject, considering the bias of other social support (subsidies). It is useful to indirectly re-recognize how the ratio of out-of-pocket expenses to the official price of public medical insurance affects the choice of consultation.
In Japan, parturition (normal childbirth), which differs from injury and illness, is not covered by the medical insurance system. This service is self-financed medical care. However, as financial support for childbirth expenditures, the Health Insurance Act provides a lump-sum childbirth and childcare allowance of JPY 420,000 per child (2021). As this system aims to reduce the financial burden of childbirth, it is also important from the perspective of measures against declining birth rates. However, the average price of childbirth is rising, and the actual cost of childbirth often exceeds JPY 420,000. Therefore, while an increase in the amount of lump-sum childbirth and childcare payments has been requested, the out-of-pocket price structure of childbirth is unclear; that is, actual costs have not been understood. Therefore, the government considers the appropriate amount of lump-sum childbirth and childcare payments to realistically grasp the situation of childbirth expenditures with services and prices.
Against the background of these trends, Japan’s regional levels of parturition prices and the factors that helped inform them were analyzed. First, a hypothesis that market principles would have a greater effect on the level formation was proposed; then, the factors that affect childbirth expenditures were structured. Consequently, price formation was considered to involve delivery costs, outcomes, supply/demand, solvency, and official (public) prices. From the provider’s perspective, “guarantee of provision cost (from a stable management viewpoint),” “overall market level and internal harmony (operation of facility),” “guarantee of quality (characteristics of the medical field),” and “competitiveness of regions (balance between supply and demand)” were selected. From the perspective of pregnant women, the elements of “interest in security (from the outcome perspective),” “interest in added value (from the amenity perspective),” “interest in the brand (from the perspective of other added values),” “restrictions on solvency (from an economic perspective),” and “access conditions (from the various types of burden)” were selected. Generally, childbirth expenditure is affected by various factors, including different factors related to facility type (e.g., general hospital, clinic, and maternity home), delivery method (e.g., natural childbirth, cesarean section, and painless delivery), timing (weekdays/daytime, night/holidays, year-end/new year), region (prefectures, cities/regions), and others (e.g., optional services such as attending a birth with family).
Consequently, the average parturition price by region in Japan was investigated. First, when the actual situation of childbirth expenditure by prefecture was analyzed using national birth-related statistical data (around 2016) [52, 53], the national average was 505,759 ± 41,906 JPY/case. A difference of approximately 1.5 times was confirmed between the highest (Tokyo City: No.1 in Figure 18) and lowest (Tottori Prefecture: No.48 in Figure 18) areas. Subsequently, multivariate analysis (multiple regression analysis) was performed to analyze the factors that differed depending on regional characteristics. Based on the factor structure described above, the objective variable was the parturition price. The explanatory variables were citizen income (solvency), “public medical expense (hospitalization unit price),” “pregnant woman’s age (risk factor),” “birth population (childbirth demand),” and “obstetric facility (supply capacity),” and “specialized equipment (maternal-fetal intensive care unit). The statistical software SPSS (IBM) was used for analysis, and the significance level was set at 5%. The results indicate that prefectural income, age at parturition, number of births, and density of equipment (facilities) affect parturition prices (Table 4). In particular, the citizen income (standard partial regression coefficient: 0.561, p < 0.001) tended to be highly related to parturition prices. The standard partial regression coefficient of birth population was negative (−0.628, p = 0.014), but the simple regression coefficient was positive (0.721, p < 0.01).
Distribution of parturition prices by region (prefecture). Note: The data source was “mean and median of childbirth costs by prefecture” (All-Japan Federation of National Health Insurance Organizations, announced in 2017).
Childbirth expenditures (normal childbirth, yen / case, FY2016) | Standardized partial regression coefficient | F-value | p-value | VIF |
---|---|---|---|---|
Annual income per citizen of the prefecture (yen / year) | 0.561 | 17.588 | 0.000 | 2.68 |
1-day hospitalization unit public price for all beds (overall: yen / day) | 0.281 | 4.106 | 0.054 | 2.88 |
Pregnant woman age (years) | 0.331 | 4.384 | 0.047 | 3.74 |
Total number of births (cases) | −0.628 | 7.011 | 0.014 | 8.42 |
Average number of births per hospital facility (number of deliveries: cases) | 0.312 | 3.272 | 0.083 | 4.46 |
Maternal and fetal intensive care unit per birth population (MFICU: number of beds) | −0.257 | 5.162 | 0.032 | 1.91 |
Decentralized analysis of the model: p < 0.001 | ||||
Socio-economic factors are affecting parturition price levels (multiple regression analysis).
Note: MFICU, maternal-fetal intensive care unit.
This chapter discussed the macroscopic mechanisms of the relationship between UHC progress and socio-economic factors to promote the sustainable development of health insurance systems. Against that background, the clinical economic considerations were presented to discuss the relationship between value and price from a micro perspective (e.g., health technology assessment).
Examining the effects of socio-economic factors of GDP and governmental health expenditures on the development of UHC showed a statistically significant positive correlation between these factors and UHC service coverage index. Furthermore, it was understood that the declining birth rate, aging population, and maturing healthcare system impacted the progress of UHC. Unemployment and poverty, distant causes of catastrophic healthcare costs, reduced the service coverage index level because of the mechanisms related to vital statistics and economic conditions. Thus, policymakers must implement countermeasures based on indicators that can estimate the economic status of the UHC approach, such as its cost-effectiveness. The sufficiency of public healthcare resources was considered important in addressing this issue. Furthermore, it was inferred that sharing healthcare values among stakeholders would be meaningful for this purpose.
Assuming that it contributes to the discussion of the real economy and official prices related to the medical field, the medical value should be evaluated by applying the marginal utility theory and cost-utility analysis. Despite some limitations, the benefits and burdens based on the value of medical care should be discussed when designing a system related to the operation of medical insurance. In this chapter, valuation research cases related to the significance of lifesaving and drug discovery were introduced, considering the possibility of allocating public resources. Furthermore, present chapter presented the price formation mechanism in the clinical field based on medical value. The price level was organized with reference to the case (childbirth) of private medical care in Japan. Factors such as the age at parturition, income level, and facility utilization rate have a price impact.
Promoting harmonization with socio-economic trends and improving explanatory power for those who bear the economic burden are key points for the future development of medical insurance systems. Long-term research using a broader range of socio-economic indicators is needed for a more accurate interpretation and deeper analysis of the obtained findings.
This study was funded by the Government of Japan Health and Labor Sciences Research Grant (grant no. JP19DA1004).
The author declares no conflicts of interest associated with this manuscript.
Trends in the country-specific economic level (GDP) and SCI components (service capacity and access). Note: UHC, universal health coverage; SCI, service coverage index [
The UHC service coverage index (SCI): Summary of tracer indicators and computation [
Overview of the regimen used (images). In this study, rituximab was administered four times every 6 months. For the first 6 months after the first dose of rituximab, the dosage of prednisolone and cyclosporine was reduced each month and stopped [
The authors gratefully acknowledge Ms. Naoko Tsukamoto and Ms. Noriko Yoshida for their contributions to the chart adjustment.
"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges".
\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.
",metaTitle:"About Open Access",metaDescription:"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges.\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.",metaKeywords:null,canonicalURL:"about-open-access",contentRaw:'[{"type":"htmlEditorComponent","content":"The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\\n\\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\\n\\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
\\n\\n“By “open access” to [peer-reviewed research literature], we mean its free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited” (reference: http://www.budapestopenaccessinitiative.org)
\\n\\nOAI-PMH
\\n\\nAs a firm believer in the wider dissemination of knowledge, IntechOpen supports the Open Access Initiative Protocol for Metadata Harvesting (OAI-PMH Version 2.0). Read more
\\n\\nLicense
\\n\\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
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\\n\\nOA Publishing Fees
\\n\\nThe Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
\\n\\nDigital Archiving Policy
\\n\\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\\n\\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
\\n\\nOpen Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
\\n\\nOpen Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
\\n\\nWe aim at improving the quality and availability of scholarly communication by promoting and practicing:
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The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\n\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\n\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
\n\n“By “open access” to [peer-reviewed research literature], we mean its free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited” (reference: http://www.budapestopenaccessinitiative.org)
\n\nOAI-PMH
\n\nAs a firm believer in the wider dissemination of knowledge, IntechOpen supports the Open Access Initiative Protocol for Metadata Harvesting (OAI-PMH Version 2.0). Read more
\n\nLicense
\n\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
\n\nPeer Review Policies
\n\nAll scientific works are Peer Reviewed prior to publishing. Read more
\n\nOA Publishing Fees
\n\nThe Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
\n\nDigital Archiving Policy
\n\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\n\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
\n\nOpen Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
\n\nOpen Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
\n\nWe aim at improving the quality and availability of scholarly communication by promoting and practicing:
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. 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The literature source was Web of Science and SSCI, SCI-EXPANDED, A&HCI, CPCI-S, CPCI-SSH, and ESCI indexes. Fifty-two articles were reviewed; however, 14 of them were not been included in the study. As a result, 38 articles were examined. Level of education, field of education, and material types of AR used in education and reported educational advantages of AR have been investigated. All articles are categorized according to target groups, which are early childhood education, primary education, secondary education, high school education, graduate education, and others. AR technology has been mostly carried out in primary and graduate education. “Science education” is the most explored field of education. Mobile applications and marker-based materials on paper have been mostly preferred. The major advantages indicated in the articles are “Learning/Academic Achievement,” “Motivation,” and “Attitude”.",book:{id:"6543",slug:"state-of-the-art-virtual-reality-and-augmented-reality-knowhow",title:"State of the Art Virtual Reality and Augmented Reality Knowhow",fullTitle:"State of the Art Virtual Reality and Augmented Reality Knowhow"},signatures:"Rabia M. Yilmaz",authors:[{id:"225838",title:"Dr.",name:"Rabia",middleName:null,surname:"Yilmaz",slug:"rabia-yilmaz",fullName:"Rabia Yilmaz"}]},{id:"59468",doi:"10.5772/intechopen.74344",title:"Virtual and Augmented Reality: New Frontiers for Clinical Psychology",slug:"virtual-and-augmented-reality-new-frontiers-for-clinical-psychology",totalDownloads:2337,totalCrossrefCites:13,totalDimensionsCites:21,abstract:"In the last decades, the applied approach for the use of virtual reality (VR) and augmented reality (AR) on clinical and health psychology has grown exponentially. These technologies have been used to treat several mental disorders, for example, phobias, stress-related disorders, depression, eating disorders, and chronic pain. The importance of VR/AR for the mental health field comes from three main concepts: (1) VR/AR as an imaginal technology, people can feel “as if they are” in a reality that does not exist in external world; (2) VR/AR as an embodied technology, the experience to feel user’s body inside the virtual environment; and (3) VR/AR as connectivity technology, the “end of geography’. In this chapter, we explore the opportunities provided by VR/AR as technologies to improve people’s quality of life and to discuss new frontiers for their application in mental health and psychological well-being promotion.",book:{id:"6543",slug:"state-of-the-art-virtual-reality-and-augmented-reality-knowhow",title:"State of the Art Virtual Reality and Augmented Reality Knowhow",fullTitle:"State of the Art Virtual Reality and Augmented Reality Knowhow"},signatures:"Sara Ventura, Rosa M. Baños and Cristina Botella",authors:[{id:"106036",title:"Dr.",name:"Rosa Maria",middleName:null,surname:"Baños",slug:"rosa-maria-banos",fullName:"Rosa Maria Baños"},{id:"227763",title:"Ph.D.",name:"Sara",middleName:null,surname:"Ventura",slug:"sara-ventura",fullName:"Sara Ventura"},{id:"229056",title:"Dr.",name:"Cristina",middleName:null,surname:"Botella",slug:"cristina-botella",fullName:"Cristina Botella"}]},{id:"59408",doi:"10.5772/intechopen.74070",title:"Enhancing BIM Methodology with VR Technology",slug:"enhancing-bim-methodology-with-vr-technology",totalDownloads:3702,totalCrossrefCites:7,totalDimensionsCites:14,abstract:"Building information modeling (BIM) is defined as the process of generating, storing, managing, exchanging, and sharing building information. In the construction industry, the processes and technologies that support BIM are constantly evolving, making the BIM even more attractive. A current topic that requires attention is the integration of BIM with virtual reality (VR) where the user visualizes a virtual world and can interact with it. By adding VR, the BIM solution can address retrieving and presenting information and increasing efficiency on communication and problem solving in an interactive and collaborative project. The objective of this chapter is to report the improvement of BIM uses with the addition of interactive capacities allowed by VR technology. A bibliographic and software research was made to support the study.",book:{id:"6543",slug:"state-of-the-art-virtual-reality-and-augmented-reality-knowhow",title:"State of the Art Virtual Reality and Augmented Reality Knowhow",fullTitle:"State of the Art Virtual Reality and Augmented Reality Knowhow"},signatures:"Alcínia Zita Sampaio",authors:[{id:"13640",title:"Prof.",name:"Alcínia Zita",middleName:"Almeida",surname:"Sampaio",slug:"alcinia-zita-sampaio",fullName:"Alcínia Zita Sampaio"}]},{id:"60066",doi:"10.5772/intechopen.75172",title:"Waveguide-Type Head-Mounted Display System for AR Application",slug:"waveguide-type-head-mounted-display-system-for-ar-application",totalDownloads:2220,totalCrossrefCites:7,totalDimensionsCites:14,abstract:"Currently, a lot of institutes and industries are working on the development of the virtual reality and augmented reality techniques, and these techniques have been recognized as the determination for the direction of the three-dimensional display development in the near future. In this chapter, we mainly discussed the design and application of several wearable head-mounted display (HMD) systems with the waveguide structure using the in- and out-couplers which are fabricated by the diffractive optical elements or holographic volume gratings. Although the structure is simple, the waveguide-type HMDs are very efficient, especially in the practical applications, especially in the augmented reality applications, which make the device light-weighted. In addition, we reviewed the existing major head-mounted display and augmented reality systems.",book:{id:"6543",slug:"state-of-the-art-virtual-reality-and-augmented-reality-knowhow",title:"State of the Art Virtual Reality and Augmented Reality Knowhow",fullTitle:"State of the Art Virtual Reality and Augmented Reality Knowhow"},signatures:"Munkh-Uchral Erdenebat, Young-Tae Lim, Ki-Chul Kwon,\nNyamsuren Darkhanbaatar and Nam Kim",authors:[{id:"36088",title:"Prof.",name:"Nam",middleName:null,surname:"Kim",slug:"nam-kim",fullName:"Nam Kim"},{id:"231071",title:"Dr.",name:"Munkh-Uchral",middleName:null,surname:"Erdenebat",slug:"munkh-uchral-erdenebat",fullName:"Munkh-Uchral Erdenebat"},{id:"231073",title:"Dr.",name:"Young-Tae",middleName:null,surname:"Lim",slug:"young-tae-lim",fullName:"Young-Tae Lim"},{id:"231075",title:"Dr.",name:"Ki-Chul",middleName:null,surname:"Kwon",slug:"ki-chul-kwon",fullName:"Ki-Chul Kwon"},{id:"249440",title:"Ms.",name:"Nyamsuren",middleName:null,surname:"Darkhanbaatar",slug:"nyamsuren-darkhanbaatar",fullName:"Nyamsuren Darkhanbaatar"}]},{id:"61026",doi:"10.5772/intechopen.76476",title:"How to Create Suitable Augmented Reality Application to Teach Social Skills for Children with ASD",slug:"how-to-create-suitable-augmented-reality-application-to-teach-social-skills-for-children-with-asd",totalDownloads:1394,totalCrossrefCites:7,totalDimensionsCites:10,abstract:"Autism spectrum disorders (ASDs) are characterized by a reduced ability to appropriately express social greetings. Studies have indicated that individuals with ASD might not recognize the crucial nonverbal cues that usually aid social interaction. This study applied augmented reality (AR) with tabletop role-playing game (AR-RPG) to focus on the standard nonverbal social cues to teach children with ASD, how to appropriately reciprocate when they socially interact with others. The results showed that intervention system provides an AR combined with physical manipulatives and presents corresponding specific elements in an AR 3D animation with dialogue; thus, it can be used to help them increase their social interaction skills and drive their attention toward the meaning and social value of greeting behavior in specific social situations. We conclude that AR-RPG of social situations helped children with ASD recognize and better understand these situations and moderately effective in teaching the target greeting responses.",book:{id:"6543",slug:"state-of-the-art-virtual-reality-and-augmented-reality-knowhow",title:"State of the Art Virtual Reality and Augmented Reality Knowhow",fullTitle:"State of the Art Virtual Reality and Augmented Reality Knowhow"},signatures:"I-Jui Lee, Ling-Yi Lin, Chien-Hsu Chen and Chi-Hsuan Chung",authors:[{id:"229636",title:"Dr.",name:"I-Jui",middleName:null,surname:"Lee",slug:"i-jui-lee",fullName:"I-Jui Lee"},{id:"250696",title:"Prof.",name:"Chien-Hsu",middleName:null,surname:"Chen",slug:"chien-hsu-chen",fullName:"Chien-Hsu Chen"}]}],mostDownloadedChaptersLast30Days:[{id:"59408",title:"Enhancing BIM Methodology with VR Technology",slug:"enhancing-bim-methodology-with-vr-technology",totalDownloads:3703,totalCrossrefCites:7,totalDimensionsCites:14,abstract:"Building information modeling (BIM) is defined as the process of generating, storing, managing, exchanging, and sharing building information. In the construction industry, the processes and technologies that support BIM are constantly evolving, making the BIM even more attractive. A current topic that requires attention is the integration of BIM with virtual reality (VR) where the user visualizes a virtual world and can interact with it. By adding VR, the BIM solution can address retrieving and presenting information and increasing efficiency on communication and problem solving in an interactive and collaborative project. The objective of this chapter is to report the improvement of BIM uses with the addition of interactive capacities allowed by VR technology. A bibliographic and software research was made to support the study.",book:{id:"6543",slug:"state-of-the-art-virtual-reality-and-augmented-reality-knowhow",title:"State of the Art Virtual Reality and Augmented Reality Knowhow",fullTitle:"State of the Art Virtual Reality and Augmented Reality Knowhow"},signatures:"Alcínia Zita Sampaio",authors:[{id:"13640",title:"Prof.",name:"Alcínia Zita",middleName:"Almeida",surname:"Sampaio",slug:"alcinia-zita-sampaio",fullName:"Alcínia Zita Sampaio"}]},{id:"59705",title:"Augmented Reality Trends in Education between 2016 and 2017 Years",slug:"augmented-reality-trends-in-education-between-2016-and-2017-years",totalDownloads:2465,totalCrossrefCites:19,totalDimensionsCites:27,abstract:"The aim of this chapter is to review literature regarding using augmented reality (AR) in education articles published in between 2016 and 2017 years. The literature source was Web of Science and SSCI, SCI-EXPANDED, A&HCI, CPCI-S, CPCI-SSH, and ESCI indexes. Fifty-two articles were reviewed; however, 14 of them were not been included in the study. As a result, 38 articles were examined. Level of education, field of education, and material types of AR used in education and reported educational advantages of AR have been investigated. All articles are categorized according to target groups, which are early childhood education, primary education, secondary education, high school education, graduate education, and others. AR technology has been mostly carried out in primary and graduate education. “Science education” is the most explored field of education. Mobile applications and marker-based materials on paper have been mostly preferred. The major advantages indicated in the articles are “Learning/Academic Achievement,” “Motivation,” and “Attitude”.",book:{id:"6543",slug:"state-of-the-art-virtual-reality-and-augmented-reality-knowhow",title:"State of the Art Virtual Reality and Augmented Reality Knowhow",fullTitle:"State of the Art Virtual Reality and Augmented Reality Knowhow"},signatures:"Rabia M. Yilmaz",authors:[{id:"225838",title:"Dr.",name:"Rabia",middleName:null,surname:"Yilmaz",slug:"rabia-yilmaz",fullName:"Rabia Yilmaz"}]},{id:"71276",title:"Use of Cloud Gaming in Education",slug:"use-of-cloud-gaming-in-education",totalDownloads:830,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The use of digital games in education has been the subject of research for many years and their usefulness has been confirmed by many studies and research projects. Standardized tests, such as PISA test, show that respondents achieved better reading, math and physics results if they used the computer more for gaming-related activities. It has been proven that the application of video games in education increases student motivation, improves several types of key skills—social and intellectual skills, reflexes and concentration. Nevertheless, there are several challenges associated with the application of video games in schools and they can be categorized as technical (network and end device limitations), competency (teachers’ knowledge in the area), qualitative (lack of educational games of high quality), and financial (high cost of purchasing games and equipment). The novel architecture for delivery of gaming content commonly referred to as “cloud gaming” has the potential to solve most of the present challenges of using games in education. A well-designed cloud gaming platform would enable seamless and simple usage for both students and teachers. While solving most of the present problems, cloud gaming introduces a set of new research challenges which will be discussed in this section.",book:{id:"7601",slug:"game-design-and-intelligent-interaction",title:"Game Design and Intelligent Interaction",fullTitle:"Game Design and Intelligent Interaction"},signatures:"Mirko Sužnjević and Maja Homen",authors:[{id:"303557",title:"Associate Prof.",name:"Mirko",middleName:null,surname:"Sužnjević",slug:"mirko-suznjevic",fullName:"Mirko Sužnjević"},{id:"316947",title:"Dr.",name:"Maja",middleName:null,surname:"Homen",slug:"maja-homen",fullName:"Maja Homen"}]},{id:"70106",title:"Categorizing Game Design Elements into Educational Game Design Fundamentals",slug:"categorizing-game-design-elements-into-educational-game-design-fundamentals",totalDownloads:1252,totalCrossrefCites:6,totalDimensionsCites:8,abstract:"Educational games have become a highly prominent tool in schools to deliver an exciting learning experience. Large amount of literature discusses the importance of how educational games are designed has been highlighted that delivering learning through educational games design and how the game designers require crucial skills to design. Educational game design requires elements which are considered during the designing process. Looking at the projection of “Game designing or the process of game design is a complex task, and it is still being investigated”. Therefore, this chapter intends to discuss recent and prominent proposed game design elements that demonstrate their important characteristics in designing educational games. Consequently, two highly significant game design theorists with established fundamental elements of games are discussed. With critically understanding the elements, this chapter provides categorizing various existing game elements into established fundamental elements. Henceforth, it demonstrates a clearer overview of how game design elements can be categorized and applied. Future recommendations are also discussed.",book:{id:"7601",slug:"game-design-and-intelligent-interaction",title:"Game Design and Intelligent Interaction",fullTitle:"Game Design and Intelligent Interaction"},signatures:"Mifrah Ahmad",authors:[{id:"303651",title:"Ph.D.",name:"Mifrah",middleName:null,surname:"Ahmad",slug:"mifrah-ahmad",fullName:"Mifrah Ahmad"}]},{id:"60066",title:"Waveguide-Type Head-Mounted Display System for AR Application",slug:"waveguide-type-head-mounted-display-system-for-ar-application",totalDownloads:2220,totalCrossrefCites:7,totalDimensionsCites:14,abstract:"Currently, a lot of institutes and industries are working on the development of the virtual reality and augmented reality techniques, and these techniques have been recognized as the determination for the direction of the three-dimensional display development in the near future. In this chapter, we mainly discussed the design and application of several wearable head-mounted display (HMD) systems with the waveguide structure using the in- and out-couplers which are fabricated by the diffractive optical elements or holographic volume gratings. Although the structure is simple, the waveguide-type HMDs are very efficient, especially in the practical applications, especially in the augmented reality applications, which make the device light-weighted. In addition, we reviewed the existing major head-mounted display and augmented reality systems.",book:{id:"6543",slug:"state-of-the-art-virtual-reality-and-augmented-reality-knowhow",title:"State of the Art Virtual Reality and Augmented Reality Knowhow",fullTitle:"State of the Art Virtual Reality and Augmented Reality Knowhow"},signatures:"Munkh-Uchral Erdenebat, Young-Tae Lim, Ki-Chul Kwon,\nNyamsuren Darkhanbaatar and Nam Kim",authors:[{id:"36088",title:"Prof.",name:"Nam",middleName:null,surname:"Kim",slug:"nam-kim",fullName:"Nam Kim"},{id:"231071",title:"Dr.",name:"Munkh-Uchral",middleName:null,surname:"Erdenebat",slug:"munkh-uchral-erdenebat",fullName:"Munkh-Uchral Erdenebat"},{id:"231073",title:"Dr.",name:"Young-Tae",middleName:null,surname:"Lim",slug:"young-tae-lim",fullName:"Young-Tae Lim"},{id:"231075",title:"Dr.",name:"Ki-Chul",middleName:null,surname:"Kwon",slug:"ki-chul-kwon",fullName:"Ki-Chul Kwon"},{id:"249440",title:"Ms.",name:"Nyamsuren",middleName:null,surname:"Darkhanbaatar",slug:"nyamsuren-darkhanbaatar",fullName:"Nyamsuren Darkhanbaatar"}]}],onlineFirstChaptersFilter:{topicId:"1318",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},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:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:317,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,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:19,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{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"}}}},{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"}}}}]},series:{item:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343",scope:"Biomedical Engineering is one of the fastest-growing interdisciplinary branches of science and industry. The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. 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Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. 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His research interests are focused on modern imaging methods used in medicine and pharmacy, including in particular hyperspectral imaging, dynamic thermovision analysis, high-resolution ultrasound, as well as other techniques such as EPR, NMR and hemispheric directional reflectance. Author of over 100 scientific works, patents and industrial designs. Expert of the Polish National Center for Research and Development, Member of the Investment Committee in the Bridge Alfa NCBiR program, expert of the Polish Ministry of Funds and Regional Policy, Polish Medical Research Agency. Editor-in-chief of the journal in the field of aesthetic medicine and dermatology - Aesthetica.",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},{id:"8",title:"Bioinspired Technology and Biomechanics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",isOpenForSubmission:!0,annualVolume:11404,editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",slug:"adriano-andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",biography:"Dr. Adriano de Oliveira Andrade graduated in Electrical Engineering at the Federal University of Goiás (Brazil) in 1997. He received his MSc and PhD in Biomedical Engineering respectively from the Federal University of Uberlândia (UFU, Brazil) in 2000 and from the University of Reading (UK) in 2005. He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). He was the head of the undergraduate program in Biomedical Engineering of the Federal University of Uberlândia (2015 - June/2019) and the head of the Centre for Innovation and Technology Assessment in Health (NIATS/UFU) since 2010. He is the head of the Postgraduate Program in Biomedical Engineering (UFU, July/2019 - to date). He was the secretary of the Parkinson's Disease Association of Uberlândia (2018-2019). Dr. Andrade's primary area of research is focused towards getting information from the neuromuscular system to understand its strategies of organization, adaptation and controlling in the context of motor neuron diseases. His research interests include Biomedical Signal Processing and Modelling, Assistive Technology, Rehabilitation Engineering, Neuroengineering and Parkinson's Disease.",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",isOpenForSubmission:!0,annualVolume:11405,editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",slug:"luis-villarreal-gomez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",biography:"Dr. Luis Villarreal is a research professor from the Facultad de Ciencias de la Ingeniería y Tecnología, Universidad Autónoma de Baja California, Tijuana, Baja California, México. Dr. Villarreal is the editor in chief and founder of the Revista de Ciencias Tecnológicas (RECIT) (https://recit.uabc.mx/) and is a member of several editorial and reviewer boards for numerous international journals. He has published more than thirty international papers and reviewed more than ninety-two manuscripts. 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Natto",slug:"herbs-and-oral-health",totalDownloads:56,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Oral Health Care - An Important Issue of the Modern Society",coverURL:"https://cdn.intechopen.com/books/images_new/10827.jpg",subseries:{id:"1",title:"Oral Health"}}}]},overviewPagePublishedBooks:{paginationCount:8,paginationItems:[{type:"book",id:"6668",title:"Dental Caries",subtitle:"Diagnosis, Prevention and Management",coverURL:"https://cdn.intechopen.com/books/images_new/6668.jpg",slug:"dental-caries-diagnosis-prevention-and-management",publishedDate:"September 19th 2018",editedByType:"Edited by",bookSignature:"Zühre Akarslan",hash:"b0f7667770a391f772726c3013c1b9ba",volumeInSeries:1,fullTitle:"Dental Caries - Diagnosis, Prevention and Management",editors:[{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",institutionURL:null,country:{name:"Turkey"}}}]},{type:"book",id:"7139",title:"Current Approaches in Orthodontics",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7139.jpg",slug:"current-approaches-in-orthodontics",publishedDate:"April 10th 2019",editedByType:"Edited by",bookSignature:"Belma Işık Aslan and Fatma Deniz Uzuner",hash:"2c77384eeb748cf05a898d65b9dcb48a",volumeInSeries:2,fullTitle:"Current Approaches in Orthodontics",editors:[{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. 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Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. 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Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. 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Currently, he is a professor of Orthodontics. He holds a Certificate of Advanced Study type A in Technology of Biomaterials used in Dentistry (1995); Certificate of Advanced Study type B in Dento-Facial Orthopaedics (1997) from the Faculty of Dental Surgery, University Denis Diderot-Paris VII, France; Diploma of Advanced Study (DESA) in Biocompatibility of Biomaterials from the Faculty of Medicine and Pharmacy of Casablanca (2002); Certificate of Clinical Occlusodontics from the Faculty of Dentistry of Casablanca (2004); University Diploma of Biostatistics and Perceptual Health Measurement from the Faculty of Medicine and Pharmacy of Casablanca (2011); and a University Diploma of Pedagogy of Odontological Sciences from the Faculty of Dentistry of Casablanca (2013). 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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}},{id:"441116",title:"Dr.",name:"Jovanka M.",middleName:null,surname:"Voyich",slug:"jovanka-m.-voyich",fullName:"Jovanka M. Voyich",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Montana State University",country:{name:"United States of America"}}},{id:"330412",title:"Dr.",name:"Muhammad",middleName:null,surname:"Farhab",slug:"muhammad-farhab",fullName:"Muhammad Farhab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"349495",title:"Dr.",name:"Muhammad",middleName:null,surname:"Ijaz",slug:"muhammad-ijaz",fullName:"Muhammad Ijaz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}}]}},subseries:{item:{id:"8",type:"subseries",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",hasOnlineFirst:!1,hasPublishedBooks:!0,annualVolume:11404,editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",slug:"adriano-andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",biography:"Dr. Adriano de Oliveira Andrade graduated in Electrical Engineering at the Federal University of Goiás (Brazil) in 1997. He received his MSc and PhD in Biomedical Engineering respectively from the Federal University of Uberlândia (UFU, Brazil) in 2000 and from the University of Reading (UK) in 2005. He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). He was the head of the undergraduate program in Biomedical Engineering of the Federal University of Uberlândia (2015 - June/2019) and the head of the Centre for Innovation and Technology Assessment in Health (NIATS/UFU) since 2010. He is the head of the Postgraduate Program in Biomedical Engineering (UFU, July/2019 - to date). He was the secretary of the Parkinson's Disease Association of Uberlândia (2018-2019). Dr. Andrade's primary area of research is focused towards getting information from the neuromuscular system to understand its strategies of organization, adaptation and controlling in the context of motor neuron diseases. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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