\r\n\tVarious disciplines characterize the constituent components comprising mechatronics, which include physical systems modeling, sensors and actuators, signals and systems, computers and logic systems, and software and data acquisition.
\r\n\tMany new MEMS and Nanotechnology applications will emerge, expanding beyond that which is currently identified or known. Here are a few applications of current interest: new phenomena are addressed nowadays in science and technology.
\r\n\tIn this book, we will deal with physical systems modeling., discuss the physical phenomena involved, the adequate methodology to deal with them, and report a selection of papers recently published for possible applications for MEMS and Nanotechnology.
\r\n\r\n\tIn summary, Nano- and micro-electromechanical systems (NEMS/MEMS) are useful for applications ranging from: The design of MEMS accelerometers, gyroscopes, electrostatic actuators, and microresonators; Interfacial engineering for NEMS/MEMS; Biosensors, magnetic biochips, in vitro diagnostics, cell sorting, magnetic nanoparticles, spin electronic materials and sensors, magnetic inductive heads, and magnetic integrated inductors and transformer’s; Flexible substrates for electronics, sensors, and energy conversion platforms; Nanofabrication and nanopatterning technologies, including self-assembly for device fabrication.
\r\n\t
Gluing is an important and integral part of the majority of timber processing and new wood product designs and developments. Investigations into the effectiveness of the gluing process, formation of the glue line and structural strength of the product relies on an in-depth understanding of glue properties, the interaction between glue and timber species and type of product. This book chapter aims to review existing image analysis and other visualisation methods used to investigate the effectiveness of the gluing process and glue line formation in timber products at the cellular level.
Wood is a non-homogenous medium with a complex cellular structure and a range of chemical compositions that varies with type (hardwood vs. softwood), species, density and surface preparation. High extractives content, sensitivity of extractives to a high temperature environment and the surface characteristics of species affects the adhesion bond formation and strength. Adhesive bonding is currently considered to be mainly a combination of three mechanisms: mechanical interlocking (through wetting of the wood surface, glue penetration and distribution and), physical attraction and covalent chemical bonding [1, 2]. Figure 1 shows a diagram of glue bond development and importance of the mechanisms leading to development of a strong glue line and good glue penetration into wood cellular structure.
Adhesive bonding mechanism including the glue and interaction between glue and timber.
The natural resinous and oily extractive content of some timbers in combination with different drying methods, or added chemicals during processing could affect the adhesive performance due to possible changes in wood surface chemistry. Adhesion is a surface phenomenon and its penetration varies with different wood surfaces, extractive contents and spatial scales of surfaces. The actual measurement and assessment of mechanical interlocking of glue in the wood industry requires more investigation and is still developing [1]. The physical attraction between the wood and adhesive in many adhesive types is considered as the primary bonding process through developing van der Waals forces and hydrogen bonds [1]. The initial surface wetting and absorption into the wood structure are fundamentally important in development of a strong adhesive profile though physical attraction. The covalent bonding between wood fibre and adhesives occur through electron sharing however, in waterproof adhesives where there are sufficient intermolecular physical attractions this electron sharing system may not be necessary [1].
The development of adhesive bonds requires wetting of the surface, flow of the adhesive into the wood structure and penetration into lumens and cell walls of wood (for some adhesive types only). A good wetting process requires formation of a low contact angle with the surface. The flow however refers to spread of adhesive liquid over the wood surface and better coverage of the surface will lead to better bond development. Penetration is the movement of the adhesive into the depth of the wood structure [3]. The overall penetration of adhesive in wood follows Darcy’s law where liquid volume flow (Q in m3.s−1) is defined as function of the specific permeability of wood (K in m2) and area perpendicular to the liquid flow (A in m2), length in flow direction (L in m), dynamic viscosity of the adhesive liquid (
Permeability plays an important role in glue bond development and low permeability of wood types (such as Douglas-fir heartwood) can cause very low penetration of resin into radial and tangential surfaces while high permeability of the wood surface can lead to bond line starvation [5, 6].
Adhesive penetration into wood can be categorised into: gross penetration and cell wall penetration [6] (see Figure 2). In gross penetration the adhesive flows into the wood porous structure filling the lumens, this type of penetration occurs in most of the resin types at low viscosity. The cell wall penetration which is the flow of the adhesive into the cell walls of woody structure is only achieved with resins with small molecular weight (MW) components. A previous study identified that a MW of 3000 for polyethylene glycol (PEG) is a critical factor at room temperature to achieve cell wall penetration in Sitka spruce. Higher temperatures could cause larger MW due to the changes in cell wall polymer and intermolecular volumes [6, 7]. Both effective and maximum penetrations are critical in achieving a good adhesive bonding [4, 6].
(Left) Imaging of effective penetration (EP) and maximum penetration (MP) of gross penetration of into structure [
Effective penetration (EP) is defined as the total area of adhesive in the interphase region of the glue line divided by the width of glue line. Maximum penetration (MP) is measured as the average value of five distance measurements taken of the five most remote adhesive objects observed in the image field [8].
As shown in Figure 2(a),
Resin viscosity, molecular weight (MW), molecular weight distribution, resin solid content and surface tension are properties of an adhesive that affect the bond development and adhesive penetration [5, 6]. Literature suggests the lower MW leads to deeper penetration of adhesive into wood structure in comparison with higher MW resins [10]. Operational factors such as open processing time, pressing time, temperature and consolidation pressure also affect the glue bond development and penetration [4, 5, 6]. Adhesive interaction with the wood surface is a function of length scale and defined as interlocking/entanglement and charge. The interlocking or entanglement interactions occur over a longer length scale in comparison with charge interaction which happens in the molecular or nano-length scale [4, 11].
Adhesive penetration is defined by the maximum depth of adhesive in wood, the thickness of the glue bond and the surface condition that affects the penetration measurement and direction. In softwood, tracheids filled with glue are visible in an interconnected zone while the process in hardwoods is more complex. In hardwood, the vessels are filled with glue but they are usually scattered and not close to the actual glue line. In softwood samples the maximum glue penetration is usually measured by trigonometric relations between the uni-directional tracheids near or around the borderline (see Figure 3). Hass et al. [12] applied a new approach in defining adhesive penetration in hardwood samples (beech) by considering pore space, ray distribution, viscosity of adhesive and bond line morphology. The study showed that the position of measurement has direct and significant effects on bond line characteristics [12]. The anatomical structure of samples, its wood type, adhesive type and their properties (viscosity for example) could all affect the penetration measurement and its replicability for various studies and products.
SEM imaging of maximum adhesive penetration in (left) softwood (spruce) and (right) hardwood (beech). The length of the scale bar in images is 200 um [
The adhesive type used in each application need to be suitable for the end use of the product as well as being compatible with the wood type and characteristics and bonding conditions [3]. Wood adhesives can be categorised by their structural, semi-structural and non-structural applications as well as the strength and durability of the bond they develop.
Polymer formation can be used to categorise adhesive types. Linear polymers develop links that are like strings of beads; polyethylene and polypropylene are two linear polymers. The other type of polymer develop branches of linear chains and the properties of formed polymers changes intensely as the branches change. As the density and length of polymers developed changes the melting point, flexibility and strength of adhesive bond changes as well [3, 13].
Self-adhesion in wood products can be achieved in certain conditions however for better strength usually adhesives are needed. Hydrogen bonding, auto-cross-linking, wood welding and rotational welding are two of the self-adhesion types. Hydrogen bonding and auto-cross-linking of the lignin and hemicellulose components in high-density fibreboard requires little to no adhesive. In high moisture and temperature conditions, softening of lignin and the hemicellulose content of wood leads to hydrogen bonding of hemicellulose joining fibres and lignin to develop chemical bonds. Through vibrational welding at high temperature and cellular distortion, bonds are developed. The bond developed has shown good strength properties in dry environments, but the strength is very low in wet conditions. Rotational welding happens when a wood dowel is driven into another piece of wood. Self-adhesion can be improved by modifying the environment (moisture, heat etc.) as well as the addition of chemicals for better bond development [14, 15, 16, 17, 18].
Formaldehyde adhesives (resorcinol formaldehyde (RF), phenol resorcinol formaldehyde (PRF, urea formaldehyde (UF) and Mixed Urea Formaldehyde (MF- including melamine urea formaldehyde MUF) are usually water borne resins and the curing procedure involves polymerisation and loss of water. The loss of water in the bond line delays the reaction of adhesives with wood due to the reduction in the wettability and movement of resin. This will limit the collision required for polymerisation process and heat transfer.
Thermosetting phenol-formaldehyde (PF) or UF are the polymers used more commonly in structural veneer-based wood product applications. For exterior veneer based wood product applications usually PFs are used and UFs are mainly used for interior applications [1]. Formaldehyde adhesives develop a rigid bond and do not creep due to combined development of polymeric chains and cross-linking groups [3, 13].
Isocyanates in wood (Polymeric Diphenylmethane Diisocyanate, Emulsion Polymer Isocyanates, Polyurethane Adhesives).
Isocyanates are used in wood adhesion due to their reactive characteristics to compounds with reactive hydrogen. These adhesives however can react very fast with wood moisture which will compete against the required reaction with the hydroxyl group in wood’s cellulose and hemicellulose and phenol and hydroxyl groups in lignin sections. The other drawback of these adhesive is their high reactivity level with the human body that could cause safety concerns during the gluing process. The most used type of isocyanates is polymeric diphenylmethane diisocynate (pMDI) in manufacturing oriented strand board (OSB) [3, 19]. PUR adhesives are also now widely in use for a wide range of application in timber products including glulam and cross laminated timber (CLT).
Epoxy resins are compounded with ketimines that assists with releasing the curing agent when the adhesive is exposed to moisture. Similar technology is already used in coating products [1]. Epoxies are produced with a range of curing times which can influence the degree of cure and mechanical strength of adhesive layer [3].
These are waterborne adhesives that are cost effective and do not require a heat curing operation and they are mainly used in furniture construction. These adhesives commonly exhibit good flow into the cell lumens that are exposed to glue however due to the high molecular weight they do not usually penetrate into wood cell walls [3]. Polyvinyl acetate (PVA) is commonly used for wood gluing in non-structural and furniture making however it lacks water resistance and has low load bearing properties.
The protein driven from wheat grain (gluten) can react with aldehydes in a similar way to urea. Gluten has a high level of amine groups (lysine and arginine) which react similarly to the ones in melamine and phenols [20]. The availability of gluten from grain is an advantage for its application in wood adhesion. However, the powder form of the gluten limits its applicability to be used in current industrial manufacturing operations.
Lignin has a phenolic structure which makes it a potential replacement for phenol in phenolic resins used for wood adhesion [21]. Lignin based adhesives can be considered in two major categories including phenol formaldehyde and formaldehyde free adhesives. Initial investigations into using unmodified lignin in phenolic adhesives showed a reduction in glue strength and an increase in press time, so chemical modification of lignin has been suggested as a solution [22]. The use of Kraft lignin and polyethylenimine (PEI) for development of a formaldehyde free adhesive showed a very high shear strength and water resistance in the glue developed [23].
In this group of adhesives depending on the role of timber in the composite there are three different product types known including: wood-fibre cement boards, wood-plastic composites and wood filler for plastics [3]. Wood-fibre cement products use the plant fibre to reinforce the panels and reduce the possibility of fracture development, this field is still under further studies. Wood-plastic combination is used to reduce the product weight for industries such as automotive industry. These products require good polymer- fibre interaction otherwise exposure of fibre to moisture and under stress the interface can fail.
These adhesives are used in construction for attaching floors and wall coverings which provide better rigidity in comparison with using nails or screws only. These adhesives do not require fast curing as the nails or screws hold the connection together while curing is completed. These adhesives have high molecular weight with minimum amount of solvent and are applied at room temperature. They are used to cover the gaps in the connected joints. The adhesives used in construction are usually elastomers to provide some deformability for small range displacement so the bond lines do not fail/crack as timber expands or shrinks. These adhesives are not designed for larger scale movements due to their high molecular weight and require checks and maintenance of the joint over time [3].
These adhesives develop bonds quickly and are used for furniture, cabinet making, windows and edge banding of laminates. The high viscosity of these adhesive limits the wetting properties of them [3].
These adhesives are high molecular weight polymers that have application in decorative laminates, tapes and labels. They are usually used in gluing plastics to wood and have different ranges for products used in indoor and outdoor conditions. Their low flow characteristics makes the pressure application important so that the force applied creates required deformation in the elastomeric adhesive [3]. In these adhesives debonding or failure of the bond developed can happen under large dimensional changes and is dependent on the stress–strain properties of the adhesive.
These adhesives are polymers in solvent and are applied on gluing surfaces and left for the solvent to evaporate before the two surfaces are brought together and pressed. These adhesives are used in bonding wood to plastic laminates.
These adhesives are expensive and are not commonly used in bonding wood. Structural acrylic and cyanoacrylate instant adhesives are two types of these adhesives that can be used for gluing wood. They require a smooth surface and are used in products that require rapid curing and high strength bonds. They are used in products such as electronics assembly or decorative layers in panel manufacturing [3].
These adhesives are used in applications where the use of liquid glue is difficult or limiting for the type of product. They are applied using an applicator such as fibreglass mat or tissue paper in applications such as gluing very thin layer wood veneers [3].
Adhesives are developed for specific applications where altering the properties of the adhesive can be required. Parameters such as surface roughness, moisture level in wood structure, cost, time between application and curing, type of production process and conditional changes (season) can influence the customisation required for formulation of adhesives [3].
The conventional microscopic imaging has been the most common and primary tool for capturing wood structure using optical waves and high magnifications to clearly capture the structure of the sample. Modern optical microscopes can generate images with 1500 times magnification with a 0.2 um limit in spatial resolution. The light transmitting through transparent sections and reflecting on the other parts of object helps in differentiating the structural components and developing clear images of the surface. Use of bright, dark, polarised, phase difference and fluorescence enhances the imageability of objects depending on the differences between the structural components [24]. It is not easy to create perfect images of a natural object using optical wavelengths due to variations in optical waves passing through the lens of the microscopes [25]. However, use of digital multimedia and digital processing technology to enhance the light microscopic system allows the collection of imaging outputs, improves the image quality and provides more image post-processing options.
Using light microscopy, the position and thickness of adhesive in lumens and other parts of the wood structure, can be captured and measured depending on wood species and adhesive types used [26]. Light microscopy can be used in generating 2 and 3D images of structures. 3D imaging of a sample’s volume can be achieved by further processing of either microtome sectioning and stacking of images using visualisation software or using optical techniques (such as light-sheet microscopy, confocal laser scanning microscopy or optical projection tomography) to mount the images taken into volumetric models [27, 28, 29]. Florescence microscopy is used to separate wood cells from the glue line [30] using short wavelength light to brighten sections of the sample [24]. Fluorescence microscopy uses a high voltage mercury lamp [24] that can improve the image quality by permitting the light excitation to irradiate the specimen and separate the weaker re-radiating fluorescent light from the brighter excitation light (Figure 4) [31].
Adhesive bond line fluorescence microscopy of an epoxy glue showing regions of glue penetration [
The fluorescence presence in the adhesive needs to be sufficient to be able to capture a clear image of the bond and glue line (see Figure 1 for more information). In order to enhance the image quality fluorescence staining can be used however sufficient power is required to produce fluorescent light [24]. Specific optical filters (each has a certain wavelength) are needed to generate images with suitable wavelength of light emitted resulting in maximum fluorescent light outputs. An aqueous mix of 0.2% of acridine yellow which is absorbed by wood but not the PF glue is used to enhance the fluorescence presence in the imaging process [31]. However the staining methods used in the literature are limited and require extra experimental steps for sample preparation, and majority of reported staining trials applied stain to the resin prior to gluing. The application of stain in industrial scale production line can be costly and cause undesirable colour changes in the product [32]. Combining images taken in visible and florescence modes (FM) can enhance the visibility of the glue line. Mahrdt et al. [32] used a merging method to combine images taken in visible and fluorescence modes using gentian violet and brilliant sulphaflavine dyes respectively (Figure 5). The merging technique improved the post-processing required for quantifying glue line parameters by allowing semi-automatic analysis of images. The most common disadvantage associated with using FM is the limitation in capturing depth which is an important parameter in glue line investigation [33].
Image of cross section and glueline using (a) visible, (b) fluorescence modes and (c) merged image [
Based on the optical path used the fluorescent microscopy can be a transmission fluorescence microscopy (TFM) or an epifluorescence microscopy (EPI) [24]. TFM usually uses a dark field passing light through a condenser to excite the sample to emit fluorescent light in different directions. TFM provides generation of strong fluorescent light in low magnifications however once the magnification increases the fluorescent light reduces making the method more applicable for larger specimens [24]. EPI uses the objective lens as a well corrected condenser first then as a light gatherer to form an image (see optical path illustration in Figure 6).
Optical path differences between (left) TFM and (right) EPI [
The images produced by TFM are usually darker in comparison with images taken by EPI. Some of the other advantages of EPI systems are increased fluorescent light intensity, reduction in light loss, no loss of fluorescence intensity [24].
Imaging of adhesive penetration into wood based composites using EPI is shown in Figure 7 [34]. The maximum penetration depth in fibres showed a rising trend as the moisture content increased. A study on the effects of moisture curing of polyurethane on the segment content (hard and soft content) of adhesive bonds showed that increasing hard phase content increased the intermolecular interactions, liquid viscosity of adhesive,and the soft phase glass transition temperature [35]. This study showed that glue bond line thickness increased as hard phase percentage increased while the hard mass percentage had a negative relation with the effective glue penetration (Figure 8).
Penetration of PF resin into poplar strands at different moisture contents of (a) 2%, (b) 6%, (c) 10% and (d) the discontinuity of glue in 6% moisture content samples [
Florescence microscopy imaging of PUR bond line and penetration development for top: PU8020 with 53.5%, middle: PU5050 with 65.4% and bottom: PU2080 with 72.5% hard phase mass [
Penetration of PF resin into poplar was quantified using EPI imaging at 2, 6 and 10% moisture content [34]. For imaging, a 50% phenol formaldehyde (PF) resin solution in water was sprayed onto the uniform oriented strand board. The mixture made of poplar and 2% potassium carbonate (K2CO3) as the catalyst was added to the strand boards [34, 36].
Using ultraviolet (UV) microscopy can generate better resolutions and higher magnification for images of glue lines. UV incident light microscopy imaging (UVLMI) was used to study the glue line in LVL samples of beech shown in Figure 9 after cyclic temperature and RH conditioning [37]. The images taken showed a clear illustration of the modified melamine–formaldehyde resin (MUF) and PUR penetration in the LVL structure. High-resolution episcopic microscopy ((HREM) uses microtome sections taking images of thin layers of the sample block (1–5 μm thick). The images are then stacked using visualisation software to develop a 3D model of the sample block. A florescence stereomicroscope and a digital camera are used to capture the dye mixture embedded in the sample block in visualising the structural components [29]. The HREM method has been successfully used in various medical applications providing better resolution imaging in comparison with X-ray computed tomography, MRI, and optical projection tomography (OPT) [28, 38]. Samples require detailed processing of dehydrated tissues prior to HREM imaging using 4% paraformaldehyde (w/v) for 1–2 hours under vacuum and then incubated at 4°C overnight before being washed by ethanol and embedded in embedding solution (Figure 10) [29].
Images of layered structure of LVL specimens conditioned in different temperature and relative humidity [
Section images of mature
To enhance the spatial resolution of microscopes, the use of electron beams is becoming a more preferred technique replacing the visible light source. Electron microscopy can reach a maximum of more than 300 million times magnification. Moving electrons can act similar to optical wavelength variation. The concept of detecting the energy release and wavelength as electrons move are the foundation for development of transmission electron microscopy (TEM) in 1938 and scanning electron microscopy (SEM) in 1952 [24]. Imaging with a higher level of magnification and in greater depth is possible using electron microscopy. However the grey colour of the images produced limits the imaging of different glue lines and sample preparation and imaging in a vacuum environment are some of the limitations for electron microscopy [24, 33].
Computed tomography (CT) was initially developed in 1970s for medical imaging, the CT scanner provides a range of image sizes including: large up to 250–500 μm or smaller μ-CT (min spatial resolution of 50 to 325 nm) and n-CT (min spatial resolution of 200 nm). For smaller size samples, reduction of the X-ray flux is required which would increase the required scanning time [27]. X-ray computed tomography (XCT) is used in microscale to image the cellular structure of samples in 3D mode providing spatial details of the complex xylem network [39]. XCT uses radiation that penetrates into the sample and then detects photons after being traversed through the specimen. XCT uses two different mechanisms to develop images of the structure: absorption contrast and phase-contrast tomography. In absorption contrast methods, the differences in material linear attenuation coefficients, μ, affects the absorption contrast resulting in sufficient contrast to map out the edges of cells in the sample structure. The linear attenuation coefficients are dependent on material density and atomic number (Z). Phase-contrast tomography uses photons incident beam phase shift at an interface between two different materials. Phase contrast tomography is suitable for materials with low absorption contrast such as soft material with a lower atomic number [40]. In wood adhesive penetration detection, the similarities between the attenuation PF and cellobiose (chosen polymer in this study to represent cell walls in wood structure) showed that XCT is not a suitable detecting method if the PF glue was tested without any contrast agent added [41]. However, this may not apply to all glue types and timber products depending on wood species, their characterises and densities (Figure 11).
Linear attenuation recorded for PF- control, brominated (BRPF), iodinated (IPF1 and 2) and rubidium (RBPF) adhesives and cellobiose as representor of wood cell walls polymer [
The lack of x-ray absorption contrast by the adhesive and the wood cells makes the use of micro CT (μCT) technology in bond line imaging and adhesive penetration challenging. The insufficient differences between the natural density of wood and the glue types used require addition of an enhancing agent to the glue for the purpose of imaging. Heavy metals have been used as contrast agent for imaging of glue line in wood products however their limited tag mobility and phase separation of those components made use of them less effective in studying the glue line properties [42]. The scanning is dependent on the absorbed contrast based on a materials linear attenuation coefficient (μ) differences. The linear attenuation coefficient is a function of material density and elemental composition. Based on Beer–Lambert’s law, μ is calculated using the transmitted (
Considering the differences between adhesives used in the timber industry and the density of commercial timber species, achieving the required contrast between the two materials will require addition of contrast agents to the wood or adhesive used. The use of contrast agent additives has been studied for wood adhesive penetration studies before [33, 40, 41, 44, 45] . From a range of tested contrast agents used with PF (see Figure 12) iodine was selected as the preferred agent, improving the clarity of differences between adhesive and cell walls. Rubidium was also tested as a contrast agent in combination with PF. RbPF (added in form of RbOH as a contrast agent to PF with molar ratio of 14.3) showed significantly clearer differences between the glue and cell walls. Use of Rb as contrast agent produced clear images and adhesive with Rb travelled easier in species with higher permeability such as oak and poplar while Douglas-fir showed lower movement of Rb in sample structure. The images taken from samples also showed that Rb travelled into the wood structure independently of the adhesive and penetrated further than the adhesive which indicated the complexity of using Rb as a contrast agent [33].
Results of imaging adhesives with different contrast agents added [
Use of x-ray micro tomography (XMT) in capturing the PF adhesive penetration in Douglas-fir samples improved the clarity of glue penetration in the sample structure however, the grey-scale results did not illustrate clearly the interface between cell walls and resin filled lumens (Figure 13).
3D images of Douglas-fir with phenol–formaldehyde adhesive in transverse surface on top (a) with the cell wall details and (b) removed cell wall details [
For clarity and image quality using XMT, samples need to be dried. The excess moisture - at saturation point can reduce the cell wall contrast and image quality. However, the oven drying of wood samples below FSP could increase the risk of cell wall collapse. Combining electron energy loss spectroscopy (EELS) or energy dispersive X-ray analysis (EDXA) with electron microscopy has shown advantages in quantifying the glue line parameters and depth. EELS uses an electron probe targeted with high capabilities in imaging dark modes (these couple weakly with the optical excitation making imaging more difficult in comparison with light mode) to map different locations of the sample [46]. The SEM-EDXA is suitable in investigating if the adhesive penetrated into the cell structure (Figure 14) [47].
EDX spectrum and backscattered SEM imaging of OSB using zinc borate as a contrast agent, arrows show the zinc borate particles in lumens of wood cell [
Iodinated (IPF) and brominated (BrPF) PF resins were used in μCT imaging of the glue lines in wood composite panels. The study of glue viscosity and MW (after curing) showed no changes in BrPF. However, the MW of glue before curing increased as percentage of added contrast agent increased. The IPF had slightly lower viscosity compared to control PF samples. The powder density determined for BrPF was lower than controlled PF samples. Further testing of tagged adhesive using fluorescent micrographs and energy-dispersive spectroscopy (EDS) elemental maps by Modzel [48] showed the presence of Rb in cell-walls in sections with no RbPF glue presence (Figure 15) [43].
X-ray images of poplar glued using iodinated PF, (a) cross section, (b) wood and bond line in 3D, (c) 3D bond line without wood sections [
In a study by Kamke et al. Iodinated PF (IPF) was made by adding 10% 3-iodophenol to plywood adhesives following commercial adhesive synthesis manufacturing process. The final adhesive had 39.5% weight iodine as the contrast agent to enhance the x-ray imaging results. Even though the viscosity of adhesive at 25C was 930 cP which could have changed the curing properties of the glue it did not compromise the behaviour of the bond. Images from this study are shown in [41]. The images generated with ionising radiation (called tomograms or slices) are obtained from the translation and rotation of the source and detectors. In this imaging technique, the attenuation coefficient of x-ray or gamma rays are recorded. In a non-homogenous medium such as wood structure it detects the attenuation coefficient depending on the quantum energy of the ionising radiation and the chemical composition of the sample [49]. The computer tomography (CT) method provides the option of imaging the full 3D structure of the sample including bark, knots, heart and sapwood borders etc. [44]. The scanning parameters measured by ionising radiation vary with wood species, size of the specimen, level of contrast in density for different defects, end use of scan information, speed of scanning required for imaging [49].
MRI or NMR was developed in 1970s for medical imaging and it was used later in the 1980s in imaging plant material [27, 50]. MRI is a non-destructive method to develop images of plant structure and has been used as an in vivo method to determine the water content and moisture movement in plant structure [51]. Images of a
Images of
Thermal technique uses the temperature to map out the surface of the object applying an active or passive heating procedure. The cyclic loading in structural timber for example can be used as an active source of heating to detect the effects of defects in structure on the mechanical strength and performance of products [49].
The passive heating process usually applies for detecting knots direction, slope of grain, moisture distribution and rupturing in wood structure. The passive heating process does not create the destructive effects on the samples due to low thermal stress however it requires fast recording methods to generate accurate images. Infrared cameras are the most common types of detecting systems using electronic detection of infrared emitted from the sample [49]. These methods are used in determining the integrity of the surface and sub-surface, for example in wood based composites [53].
Scanning thermal microscopy (SThM) uses two different modes to detect the changes in chemical composition of samples and map out the adhesive penetration in the structure using a thermal probe. The thermal contrast microscopy (TCM) measures the changes in temperature of the sample surface. Conductivity contrast microscopy (CCM) also measures the sample’s surface conductivity as the temperature is kept constant [54]. Images of wood phenol-resorcinol-formaldehyde-adhesive bonds (PRF) using SThM are presented in Figure 17.
(a) Images of adhesive bond in spruce samples using (top): Light microscopy and (bottom): SThM mapping the topography, probe current and voltage and (b) differences in topography for SPURR epoxy resin (Centre) and in contact with PUR adhesive (left) and PRF adhesive (right).
In microwave techniques, Dielectric properties of the sample structure are used to image the structure in microwave imaging methods. This method is commonly used for assessment of wood products after drying and gluing, for detecting any internal detects such as knots, spiral grains, discontinuation in structure of logs, lumber and wood based composites [49].
Ultrasonic methods are low cost methods for detecting the adhesive content of wood products with a high sensitivity to delamination, however achieving imaging with high resolution is difficult and coupling pressure dependency reproducibility of this technique is poor [44]. There have been reported studies on the uncertainty around voltage values that the tranducer recorded (20–25% variation) where extra applied hand pressure is required for ultrasonic readings [55]. Air coupled ultrasonics systems however have shown promising results eliminating this variation which requires future investigation on its effectiveness in detecting complex glued sections (Figure 18) [44, 55].
Microwave technique used to detect knots in radial (a) and reconstructed image (b) [
FTIR imaging of chemical components (Fourier Transform Infrared) provides details of functional groups based on absorption, of chemical band intensity, band areas, and position. Figure 19 shows the FTIR readings for wood and Polymeric diphenylmethane diisocyanate (pMDI) in uncured and cured conditions [56]. This study reported on the challenges in detecting glue formation in the cell walls using this method.
Results of imaging using FTIR spectra of loblolly pine (
Chemical imaging is used to map out the intensity and distribution of different components in wood structure [57, 57]. The study used non-covalent interaction of acetylated nanocrystalline cellulose (AC-NCC) with polylactic acid (PLA) in material tested as an indicator for chemical imaging. Figure 20 shows the readings for different chemical components in the samples including visible light image in left column, mCH2 absorption maps in middle column and integrated mC=O second derivative absorption peak areas in right column. The results showed that FTIR imaging can be used effectively to image the chemical links between a substrate and functionalised filler [57].
Results of absorption map for different particles using chemical imaging and FTIR micro spectroscopy for composite materials [
As discussed earlier, X-ray computed tomography (XCT) was used after adding the bromine substituted phenol formaldehyde (BrPF) to increase the X-ray attenuation and capture a brighter glue line which is distinguishable from wood cells [58].
This study also used X-ray fluorescence microscopy (XFM) to acquire images of the bond line [59]. This study investigated the required adhesive (BrPF) flow and infiltration to develop an effective glue bond in loblolly pine (
Left- X-ray computed tomography (XCT) and right- X-ray fluorescence microscopy (XFM) images of glue line [
The XCT method provides the option of visualising the flow of BrPF and penetration into the 3D wood structure over time. In sections with less clarity of BrPF mixed with wood, XFM provided a detailed observation for the glue presence inside the cell structure of the wood (Figure 22).
Flow of BrPF into wood structure over time [
A study of PF in wood cell walls using XFM in combination with nanoindentation showed that using BrPF enhanced the cell wall matrix (see sections showed in Figure 21). The different molecular weights (MW) of BrPF tested showed that the lower MW had greater effects on preventing the softening of cell walls due to gained moisture. In Figure 23, the glue line is shown by arrows and the dashed white line shows the cells that were tested for mechanical strength using nanoindentation [59].
XFM used to map Br penetration into wood cell structure, (a) after 85 min BrPF and (b) 155 min samples [
Nano indentation and scanning probe microscopy (SPM) imaging of year old Masson pine (
Images of Masson pine (a and c) under microscope and (b and d) under SPM equipped with nano indenter probe [
EPI microscopy can provide imaging of the cell structure from the surface of samples used for imaging.
A study of adhesive penetration in particle board composites using EPI showed this microscopic method was effective for quantitatively assessing glue interaction with wood. The study determined adhesive filled fibre numbers (FFN), adhesive filled vessels number (FVN), maximum adhesive penetration depth in fibre (MPDf) and in rays (MPDr). Figure 25(a) shows the results of EPI microscopy in poplar samples at different moisture content (2, 6 and 10% MC) [34]. Penetration of resin was higher in higher moisture content wood. Figure 25(b) shows results of EPI imaging of three UF adhesives in poplar in radial and tangential directions. The images taken showed clear sections where glue penetrated into vessels, rays as well as showing the bond lines. Three UF adhesives were tested at different viscosities including UF I, 545 mPa.s < UF II, 745 mPa.s < UF III, 1644 mPa.s [36].
(a) Images of UF penetration into wood structure using EPI [
This study showed penetration into the radial direction was lower than penetration in tangential direction which could be related to the presence of pits (on radial walls) that facilitate the adhesive movement in tangential direction. Shear strength of specimens increased as penetration increased and was higher in adhesive with lower viscosity (due to better flow of adhesive) [36].
Confocal laser scanning microscopy (CLSM) provides an optical depth selection option to image the sections of a structure that are usually very hard to physically prepare. Imaging of glued sections using CLSM under FM provides a clear representation of the glue line and its borders in wood structure. Figure 26(a) represents the images taken from a coated wood surface in a study investigating the durability of the coating material used and penetration into surface cracks of radiata pine (
CLSM used in (a) imaging coating surface and penetration of coating material into the wood structure (bar = 20 μm) [
The separation between urea formaldehyde (UF) resin and wood cells is not usually easy with common microscopic methods; Figure 26-right show images of UF resin using CLSM [9].
Figure 26(b) shows results of CLSM of UF resin penetration in radiata pine (
CLSM has also been used in imaging different particle board samples targeting the UF resin component in board structure enabling the quantification of resin percentage in the total board area. This study which combined CLSM and fluorescence labelled UF (Figure 27) showed clear sections of cells and glue penetration into the structure of boards (made from Norway spruce (
Images of particleboard section glued using fluorescence-labelled UF resin, bar = 50 μm [
Left- light microscopy image with high magnification, middle- image taken using confocal florescence micrograph and right- SEM image [
Chemical mapping and imaging of biological and biometric samples- FT-Raman spectroscopy- has recently been used in studying wood including coatings, degradation and modification of cell walls. Similar to NIR detecting systems, Raman spectroscopy uses the vibrational transitions [65]. However, Raman spectroscopy uses the changes in polarizability of functional groups while NIR uses differences in infrared absorption to detect chemical components. A study of Japanese cedar (
Raman mapping on cross section of coated samples of Japanese cedar (a) Raman image (b) lignin, (c) alkyd resin and (d) merged information adrenal glands [
Similar work done by Wang et al. [60] showed the advantages that Raman spectroscopy can provide in studying the penetration of PF resin into the cellular structure of Masson pine. The images indicated the penetration of PF resin into cell lumens as well as into cell walls. The images also show the interaction of the PF with polymers in the cell walls. The nano indentation done on cell walls in combination with the Raman spectroscopy conducted showed that the added PF resin in the wood structure reduced the dimensional changes of the structure resulting from swelling and shrinkage [60].
The review focuses on existing studies and techniques used for visualising adhesive bonds in various timber products. This review highlighted the capacity, advantages, limitations and the potential of the different visualisation methods including Microscopy (visible light, UV, IR), Electron Microscopy (SEM, ESEM, transmission electron microscopy (TEM)), X-ray computed tomography (XCT), Thermal techniques, Microwave techniques, Ionising radiation, Ultrasonics, FTIR imaging of chemical components, X-ray imaging, Epifluorescence Microscopy (EPI), Confocal laser scanning microscopy (CLSM) and Chemical mapping. The majority of work published has focused on applications and types of wood used for specific products rather than developing/following a standard protocol in determining definitions for adhesive bond development and measurements. These studies are mainly qualitative and comparative only to samples tested in each study. The review suggests that there is a need for developing standard definitions for glue bond shape, thickness, penetration depth and scale in both 2 and 3D in order to be able to quantitatively assess the effectiveness of gluing process for various timber products. The effects of wood types, anatomical structure, gluing properties, curing mechanisms and glue types used for different applications/products need to be studied for different structural and non-structural timber elements. The review also highlighted the need for better definitions of glue lines, penetration in relation to wood grain direction and cellular details which could affect the penetration effectiveness depending on surface wetting properties, extractive content in cells and size of cells. The interaction between glue, cell walls and chemical extractives of different wood types before and after glue application and product manufacturing will need to be carefully studied and a summary of potential differences and similarities for each type of timber product can be developed for industry to access.
The existing literature shows the strength and capacity of different visualisation methods for analysing the adhesive effectiveness in different wood types, however more research is required to examine the potential of each method for a range of timber products and wood types (e.g. soft vs. hardwoods). The 3D imaging can provide detailed information on adhesive bonds in various conditions including where there is variation in MC, glue type (different curing requirements and curing time) and wood type (including low to high density and for soft and hardwood).
In the use of X-ray scanning where density differences between the wood and glue are the main visualisation factor, further studies are needed for investigating the effects of adding contrast agents (such as iodine) to adhesives and the potential effects on glue properties that could lead to bond line variations and changes in penetration patterns.
Further work is required to monitor potential effects of industrial processes and environmental conditional factors on bond formation and adhesive penetration during and after production and in the service life of timber elements specially for structural products such as glulam, CLT and LVL.
The authors acknowledge the Queensland Department of Agriculture and Fisheries and the Australian Centre for International Agricultural Research (ACIAR) for providing the funding which supported this work, as a component of the ACIAR Project FST/2016/151 “Advancing enhanced wood manufacturing industries in Laos and Australia”.
Death is often considered in terms of medical, legal, ethical, philosophical, societal, cultural, and religious rationales. The biomedical definition of death is primarily a scientific issue supported by the best available evidence. A medical practitioner has certain ethical and legal responsibilities regarding death, such as the effort for prevention of death, determination of death, determination of time/moment of death, declaration of death, issuing the certificate, and if needed, autopsy or organ removal for transplantation. That aspect has a lot of ethical, legal, emotional, and scientific issues. Dying is considered as a process, which affects different functions and cells of the body at different rates of decay. Doctors must decide at what moment along this process there is permanence and death can be appropriately declared. Diagnosis of death and a record of the time of the death, in most countries, are the legal responsibility of a medical practitioner. Determining the moment of death is vital to avoid the use of unnecessary medical interventions on patients who have already died and to make sure that the method of organ donation is obvious and transparent. Also, the time of death is important because of survivorship clauses in wills.
For the millennia, human has struggled with the concept and criteria of death, and thus, the line between life and death continues to be debated. The profound changes caused by the life support in organ failure, organ substitution technology, and transplantation still continue to challenge our notions of life and death [1]. Despite scientific progress in the last few decades, there remain big variations in the diagnosis criteria applied in each country with legal regulations resulting in misunderstandings among the public and health care professionals. Since the ample decades, the academic literature and the media have raised the voice in alarming language in issues of death determination and dead donation practices [2]. Difficulty arises to distinguish valid scientific critique from those criticisms supported by the fear of death itself, mistaken diagnosis or a premature declaration of death, or the fear of retrieving organs from the living.
The challenges in discussions about death are complex due to philosophical, religious, and cultural differences in the concept and definitions of death; debate about ethics, law, and religion; problems in performing research and the resultant shortfall in information and evidence on various aspects of the dying process; dispute in the validity of death determination practices; lack of understanding and/or awareness by general public and health professionals; last but not the least the emotionally charged nature of the subject matter. There are plentiful ways of dying but just one way to be dead. Hence, the baseline determination of death criteria should be rigorous, global, and acceptable for medical practice worldwide, while remaining respectful of diversities. International consensus on the clinical criteria for the death determination is of central importance to preserve public trust and promote ethical practices that respect the fundamental rights of people and promote quality health services [3].
In medical practice and law, the separation between being alive and dead should not be ambiguous. It designates the moments that follow events such as no medical or legal need to maintain resuscitation or life support, loss of personhood and individual rights, decedent’s legal will execution, disposal of the estate, life insurance settlement, burial or cremation of the body for final disposition, and religious or social ceremonies to mark the end of a life [4]. Dying is not an event rather a process, which affects various functions of the body at different rates of decay. The physician must confirm the moment along this process that there is permanence and death can be accurately declared [5]. Biological criteria of death are associated with biological features and irreversible loss of certain cognitive capabilities [6]. A patient could be declared dead legally as lack of brain function and may still have a heartbeat when on a mechanical ventilator. Though there is no justification in supporting the ventilation of a dead person, withdrawing the ventilator before the legal criteria of death may involve the doctor in both civil and criminal proceedings. The legitimate moment of death could be a wide range of time after the death has actually occurred. Many accident victims actually died at the scene of the accident but were declared dead officially on arrival at a hospital.
The scientific, biological, and medical aspects of the determination of death are still controversial. Certain ancillary and/or complementary laboratory tests could also be useful in situations where clinical testing cannot be executed or if confounding or special conditions are present. It had been recognized that there are limitations to the utilization of a number of these tests and further work will confirm the reliability of these tests. Death is a biological phenomenon, with profound social, religious, and psychological traditions, but very little background experience and available scientific information. The understanding of the biological aspect has gradually developed and strengthened as a direct result of technology, cell biology, organ donation, and transplantation, but was inadequately adjust in law, health policy, and bioethical discourse. Organ donation has forced the understanding of moment of death and acceptance or persisting controversy of where that line is.
It is urgent time demanding notion to adopt a minimum determination of death criteria to be acceptable for medical practice worldwide to achieve international consensus on clinical criteria to maintain public trust and promote ethical practices.
The concepts and practices of death undoubtedly are influenced by values and social practice. The definition of death affects not only that consider to count as death, but also questions of grieving, medical treatment, asset disposal, organ donation, and a myriad of other legal and ethical issues [7].
The philosophical investigation of human death has focused on some overarching questions—What is human death? The conceptualization (definition) of death is the answer to this ontological question that defines death as the irreversible cessation of organismic functioning along with the irreversible loss of personhood. Next question, how can be determine that death has occurred? The answer is epistemological one, which furnishes both the
Finally, how do the deaths relate, conceptually, to the essence and identity as human persons? The metaphysics of the body and soul does so in terms of the logical dualism between the material body and consciousness or the immaterial mind. In the philosophy of mind, mental phenomena are nonphysical and thus distinct and separable from the body. The dualism of body and soul/mind suggests that while being a person is, undoubtedly, a matter of having a biologically human body. The existence of a person entails the presence of a thinking being, which has reason and reflection, and can consider itself as itself, in different times and places. The individual identity of psychological persons is dependent on the brains’ neurophysiology [9]. The brain death need not be considered as biological death rather a proxy for the loss of individual identity, that is, personhood [10]. When a person has died, it does not merely mean that some biological entity no longer functions. It means some unique mind or person, realized as a cognitive or psychological entity, has ceased to exist. The personhood admits of application of the terms life and death. It has been exceedingly rare for the demise of a biological human organism to take place sometime after the death of a person. Artificial life support can maintain the biological life of an individual in the absence of their continued psychological existence. Such brain dead individuals have been considered living cadavers and twice dead [11]. Human life is operationally defined by the onset and cessation of organismal function [12]. There are two different meanings to human death being alive and having a life, the notion of personhood allows us to focus on the autobiographical meaning of death—the loss of a person [13].
Other philosophical questions—When does a human being die? Is the organismic and denouement conception of death have any practical use? Schofield et al. present a definition of death focused on the final denouement of human beings as biological organisms. According to their view, the moment of death is the last process in bodily functions that maintain homeostasis and finally ceases [14]. Reducing death to the biological denies an important characteristic of being human, intellectual, or psychological nature. The conception of death acknowledges the cognitive aspect of human existence, at the same time, accommodating embodiment, that we both have and are biological bodies [15].
Generally, people believe that death terminates the whole existence of a person. According to Christians’ belief, death puts an end to human existence on earth but does not end existence, instead opens an entrance into another sphere where existence continues either in heaven or hell after the final judgment that everybody will face it. Death is considered
Life is fundamentally grounded on the continuation of individual and collective cell function, dependent on the supply of nutrients and oxygen. Cell biology has exhibited that a layer of human cells, separated from the human organism, could also be grown in laboratory culture pending till bathed in a steady supply of nutrients and oxygen. The human being, a complex package of trillions of cells organized into organ systems, requires a cardiopulmonary delivery system for oxygen and nutrients to reach the cells. The development and evolution of modern cardiopulmonary resuscitation evolving into cardiopulmonary support technologies have been important advances informing our concepts of life and death.
The introduction of advanced medical technology poses new problems for the old standards that constitute death. The values automatically shape thinking of the death of a person, not merely a descriptive, scientific concept, but unequivocally contain evaluative content. The changing frontiers of the death drive to confront basic questions of persons and values that will adapt to address future questions. It is vital to examine the evaluative content of concepts and practices relating to death, and reflects on what it is that we value or should value in persons. The philosophical definitions of death in the absence of indisputable objective signs of death should be considered, loss of integrative functioning of the whole organism, failure to engage the environment spontaneously by respiration, loss of consciousness and sentiency, and the separation of some vital principles from the body.
The neurological criteria for death represent an interesting advance in the ways of responding to changes in death and dying. The development of medical technology and life support techniques insist increasingly on precise notions to identify the most important aspect of neurological lives. However, the whole brain standard of death suffices in the vast majority of cases, but does not fully line up the value in persons. Time has come to decide the position of the current brain death standard as it mismatch with the values and negative consequences in determining death and in organ donation. Advances in technologies seem as if they will inevitably make this question inescapable. The prominence of
Ideally, the definition of death would link the concept of life or death with its clinical manifestations as closely as possible that fall in both two categories, the
Death is the transition from being a living mortal organism to being something that, though dead, retains a physical continuity with the once-living organism. Death is a process involving the cessation of physiological functions and the determination of death is the final event in that process. Death is a gradual process at the cellular level with tissues varying in their ability to withstand deprivation of oxygen. A distinction is now being made between death at the cellular and tissue levels and death of the person. Sydney declaration states, clinically, death lies not in the preservation of isolated cells but in the fate of a person. Korein’s view of the life of the multicellular organism as a whole could no longer be explained in terms of a cellular task alone. The life of a typical unicellular organism encompasses fundamental tasks of the metabolic and reproductive attributes of a particular organism, empowering it to amplify in a direction of decreased entropy production (bacteria, amoeba, or zygote). In a multicellular organism, a large mass of cells could be alive but this does not indicate that the organism as a whole was alive. Machado refused the hypothesis that an explanation of death should include the function that contributes to the key human attributes and the highest level of control in the hierarchy of integrating functions within the human organism [18, 19, 20, 21, 22, 23, 24].
The full version of death includes three unique ingredients such as the definition of death, yardstick of brain death, and the tests to prove that the standard has been satisfied. The definition of death is typically a philosophical task, while the criteria and tests are medical tasks. Particular standards and tests must match with a given definition. The definition must represent attributes that are so important and significant to a living entity that its absence is designate death [25, 26]. The nonfunctioning entire brain provokes the permanent cessation of the functioning of the organism as a whole.
Biologically death is defined as the extinction of biological properties of life. Human death can be defined as the irreversible cessation of three interdependent and interlink vital functions of the body—the tripod of life (heart, lung, and brain). Another way death can be defined as a person is said to be dead, if he cannot take up spontaneous respiration or maintain circulation. There is growing medical consensus in a unifying concept of human death, which involves the irreversible loss of the capacity for consciousness, combined with the irreversible loss of the capacity to breathe.
Uniform determination of death (UDDA) act defines death as, an individual who has sustained either irreversible cessation of circulatory and respiratory functions, or irreversible cessation of all the functions of the entire brain, including the brain stem, is dead. Montreal forum defines death as the irreversible loss of the capability for consciousness and loss of all brainstem functions. That could result as a consequence of permanent stoppage of circulation and/or after catastrophic brain injury. In the determination of death, “permanent” refers to the cessation of function that cannot resume automatically even not be restored through intervention. The determination of death must be made in accordance with accepted medical standards.
The presence of the two vital functions, circulation and respiration in a body, is a sure sign of life. The patient who was diagnosed with entire brain failure and has been pronounced dead the vital functions are dependent on external support from the ventilator. The supporter of neurological standard designates these apparent signs of life are artifacts of the mechanical support that conceal the very fact that death has already occurred. To judge that logic, the essential facts of mechanical assistance for these vital functions be achieved if the interrelationship of three-body systems involved in breathing and circulation is understood. The three systems are the heart and circulatory system, the lungs and respiratory system, and the central nervous system. The pathophysiological processes that eventually end in mortal condition,
The prime functions of respiration are ventilation and diffusion. The ventilation involves both inhalation and exhalation; the diffusion involves the exchange of oxygen and carbon dioxide between atmospheric air and blood. The respiratory system brings atmospheric air by inhaling process to the alveoli where oxygen from the atmospheric air is able to move into the blood by the process of diffusion. The exhaling process of breathing facilitates to rid the body of the waste products—carbon dioxide. The walls of the alveoli are extremely thin, formed to facilitate the diffusion of gases between the sacs and the blood vessels. Oxygen is essential to the continued metabolic work of the trillions of cells in the body. The absence of an endless delivery of oxygen, brought into the body through inhalations and transported to the tissues by the
The CNS plays a crucial role in maintaining an organism’s vital functions. The reticular activating system of the brainstem is also critical to the organism’s conscious life, essential for maintaining a state of wakefulness, which is a prerequisite for any of the activities associated with consciousness. The contraction of the muscles of respiration is brought about by a signal sent from the respiratory center located at the brainstem. A relatively high level of CO2 in the blood stimulates the respiratory center to send a signal to the muscles of respiration, which excites them to contract. For life to continue, the CO2 must be expelled and new oxygen brought in. Other parts of the CNS also be involved in signaling the muscles of respiration to contract, like
To prevent the death of the organism, some external device (mechanical ventilator) for the breathing process is essential. The mechanical ventilator works by altering the pressure in the lung cavities in order that oxygen-rich atmospheric air will travel down and CO2-rich air will travel back up the respiratory tree. Gas exchange in the lungs will be of no benefit to the patient unless the blood is kept moving as well. Incoming oxygen must be delivered to tissues that required it, and accumulating carbon dioxide must be a shift to the lungs for expulsion from the body. Hence, a ventilator will help the patient as long as another vital system is functional, constituting the heart (working as a pump) and network of arteries, veins, and capillaries. The movement of blood occurs only within the body, whereas the movement of air is an exchange between the body and the surrounding atmosphere. Another relevant rationale of external support of vital systems is the indisputable fact that there is no part of the CNS that is absolutely essential for heart contractions within the way as the respiratory center in the brainstem is unconditionally essential in breathing. The heart is the most essential active part of the circulatory system and the vessels of circulation, being rigid plumbing lines that passively convey blood, pumped by the heart, are living tissues that undergo changes (some driven by CNS) to sustain a proper blood pressure. Patients of ventilator support must also be given drugs to maintain the blood pressure in a healthy range. Ventilator support designates the external supports of vital functions of breathing and circulation, in lieu of breathing effort of organism, stimulated by the respiratory centers of CNS, an external device moves the lungs and facilitates the inflow and outflow of needed air. It offers the heart muscle still to function, as the myocardium, like other cells in the body, needs oxygen to stay alive. The argument for the neurological standard of determination of death begins with facts that the respiratory motion supported in this way is not in itself a symbol of life, rather an artifact of technological intervention. Neither a beating heart, in this instance, a symbol of life, or merely the continuation of a spontaneous process would quickly cease if the ventilator is withdrawn [27].
Humans have long used criteria and technology to assist in the diagnosis of death. The link between breath and life is equally as ancient and found in both Genesis (2:7) and the Qur’an (32:9). Somatic criteria, such as the presence of decomposition and rigor mortis, are the oldest in human history. Over 800 years ago, when Maimonides codified the diagnosis of death as the absence of the heartbeat and respiration with cooling of the body [28], he was likely documenting a standard used from down of civilization.
In the eighteenth century, the physician was confirmed about death if the heart and lungs break off, but lacked adequate tests to certify it. In the twentieth century, the moment of death became less clear, and thus, the tests physicians had finally perfected proved insufficient. Historically, until the early twentieth century, physicians’ inexperience in human anatomy and physiology left them poorly equipped to accurately test for death. From the eighteenth through the mid-twentieth centuries, a person was declared dead when the heart stopped beating and lungs ceased to function. In the early part of the twentieth century, while the standard to check death was well established, the understanding of when the death occurred became the subject of great debate. The fear of premature burial was replaced by the fear of apparent death sustained by life support systems. These issues reach a climax in the latter part of the twentieth century when the cardiorespiratory definition of death was reevaluated and a novice addition of brain death was introduced. Intensifying new questions as to the moment of death, the brain death criterion demands further revision of the empirical tests. The nature of death, however, does not lend itself to one discipline rather considers metaphysics, sociology, theology, and medicine. Historically, the irreversible stoppage of heart and lung functions constituted death as the absence of heart and lung activity immediately leading to failure of the entire organism. It has become apparent that cardiac and respiratory activities were significant for separating the living from the dead. The moment of death was firmly estimated but the task of confirming criteria to check for irreversible quiescence of functions proved more challenging and often had catastrophic consequences. A consensus emerged that once the heart and lungs ceased to function the person was dead, although the empirical criteria to test for death were suspect. Because of this critical divide between theory and practice, instances of premature burial occurred. To safeguard premature burial date back to antiquity with the Thracians, Romans, and Greeks, each waited 3 days for putrefaction to start before burying their dead. The Romans took a more extreme approach by amputation of a finger to ascertain if the stump bled, in addition to calling out the person’s name three times while on the funeral pyre. Hence, the premature burial was a great worry, though it did not attain climax until the eighteenth century, accelerated by the intellectual climate. The knowledge and scientific revolution instituted a radical change in the insight of life and death [29].
Belief in the afterlife was not as important as life here due to the works of Bacon, Descartes, and Galileo, which emphasized the notion that life might be improved if not perfected by scientific manipulation. There is little practical obligation to worry oneself with an afterlife if this life could be manipulated by the art of medicine. Revulsion (drawing of disease) by the dissection of cadaver found in the sixteenth and seventeenth centuries as the study of human anatomy revealed the secrets of the
During this era, fear for early burial was so prominent that led to the establishment of waiting mortuaries and security coffins with alarm mechanisms and permanent air supply. The “Academy of sciences prize” was awarded in 1846 to Dr. Eugene Bouchut for his best work on the “signs of death and the means of avoiding premature burials.” He suggested the utilization of the stethoscope, invented in 1819 by Laennec, as a technological aid to diagnose death. Other popular practices for death determination were inserting leeches near the anus, applying specially designed pincers to the nipples, or piercing the heart with a long needle with a flag at the end, which wave if the heart is still beating. Bouchut suggested that a person could be declared dead if a heartbeat was absent for 2 min. He extended the period to 5 min, in the face of opposition [36, 37, 38, 39]. Case reports from physicians (Harvey Cushing) writing around the beginning of the twentieth century had evident that patients of cerebral pathology would die from respiratory arrest and subsequent circulatory collapse. Loss of electrical activity in the brain and cerebral circulatory arrest might signify human death that was evident in subsequent decades. The advent of mechanical ventilation, halting the inevitable circulatory collapse that follows the cessation of spontaneous respiration with the advent of mechanical ventilation, and the relevance to diagnosing death using neurological standard were understood.
In 1959, two historical landmarks were published, Mollaret and Goulon proposed the term
A group of anesthesiologists observed problems of sustaining the body alive in the absence of total brain function. This problem was presented to Pope Pius XII and resulted in the publication of a papal allocution describing that
The papal allocution culminate research, by three categories of French neurologists and neurophysiologists during 1959, separately studied comatose and apneic patients separately, narrated terms death of the “systema nervosum and coma de´passe´” translated as beyond coma or ultra-coma and subsequently by others as irreversible coma. These patients were respirator dependent, in an unresponsive coma, and areflexive. EEG and deep intracranial electrical activity were entirely absent. The investigators’ conclusion was that the brains of these patients were irreversibly dysfunctional. The WMA ethical committee and its council undertake dialogue and conference on death, 2 years earlier the first heart transplant by Christian Barnard in 1967. Wijdicks wrote that the first idea for the formation of the Harvard committee was recorded in a letter from Henry Beecher to Robert H. Ebert in September 1967. The Sydney and Harvard committees worked in parallel for several months, without either being aware of the other’s work [41, 42, 43, 44, 45].
The year 1968 was a crucial time for defining human death on the neurological ground and a milestone event in the history of medical science. On August 5, 1968, the Ad Hoc committee of the Harvard medical school to examine the definition of brain death published a report, as
Since 1968, the concept of brain death has been extensively analyzed, debated, and reworked. Still, there remain much misunderstanding and confusion, especially for the general public [50]. The Declaration of Sydney touched on key philosophical issues on human death. It proclaimed that in most situations physicians could diagnose death by the classical cardiorespiratory criteria. In spite of this, two modern practices in medicine force them to revise the time of death: first the ability to maintain circulation by artificial means and second the use of cadaver organs for transplantation. The essential public addresses death as a progressive process at the cellular level with tissues varying in their capability to cope with deprivation of oxygen, but clinically death “lies not in the preservation of isolated cells but in the fate of a person.” Also, it is described that the death determination must be grounded on clinical judgment, supplemented if necessary by a number of diagnostic aids, emphasizing the EEG. Nonetheless, it asserted that the overall judgment of the physician could not be replaced by any ancillary test. The declaration went further, proposing a more philosophical and conceptual explanation about the relationship between death and the fate of a person. The Harvard committee did not provide a clear concept of death but emphasized a clinical explanation of brain death, describing in detail the anatomical substratum and tests. The Sydney declaration did not use the term brain death but declared the clinical judgment for death determination and the Harvard committee, although mentioned the term brain death, finally select irreversible coma along with a detailed set of clinical criteria for death declaration. Both the Sydney and the Harvard committees suggest the use of EEG. For the purpose of the death diagnosis and transplantation, the Sydney declaration advocates two or more physicians not involved in transplantation should make the diagnosis, while the Harvard committee voiced that the death declaration should be made first, and then, physicians not involved in the transplantation procedure should be the one to turn off the respirator. Both committees justify a legal regulation of this issue [49]. Sydney declaration was amended at 35th WMA, by the addition of a key point declaring that “It is essential to determine the irreversible cessation of all functions of the whole brain, including the brain stem” for diagnosis of brain death but the EEG was not mentioned and no other issues were modified [49, 50].
In July 1981, the President commission for the study of ethical problems in medicine and behavioral research published a report,
A scientific basis was suggested to justify brain death with the theory of the brain as the central integrator of the body. According to this theory, the organism becomes a rapidly disintegrating collection of organs following the brain death (BD). Consequently, the concept of BD is not only an ethical and/or social concept or a matter of values, rather a matter of scientific facts such as irreversible stoppage of functioning of the organism as a whole is death. The guiding principles of irreversible cessations of functioning of the entire brain are absolutely correlated with the permanent cessation of functioning of the organism as a whole as the brain is necessary for the functioning of the organism. The brain integrates, generates, interrelates, and controls complex bodily activities. A patient on a ventilator with entirely destroyed brain is merely a group of artificially sustained subsystems since the organism as a whole has ceased to function. President’s Commission report also supports that rationale, convincing the gravity of the brain and recognized the profound instability of the brain-dead organism. In adults who have an irreversible stoppage of the whole brain’s function, the mechanically generated functioning could exist only for a limited time as the heart usually stops beating within 2–10 days [51].
The enabling legislation for the President’s Commission directs it to study the ethical and legal implications of the matter of defining death, including the probability of developing a uniform definition of death [51]. The central conclusions were that the recent developments in medical treatment necessitate a restatement of the standards traditionally recognized for determining that death has occurred and such a restatement ought preferably to be a matter of statutory law, which should be uniform among all the states. The definition embodied in the statute ought to address general physiological standards instead of medical criteria and tests, which will change with advances in biomedical knowledge and refinements in technique. The death is a unique episode that could accurately be confirmed either on the traditional grounds of permanent cessation of heart and lung functions or on the basis of permanent loss of functions of the entire brain. Any statutory definition must be separate and distinct from provisions governing the donation of cadaver organs and any legal rules on decisions to terminate life-sustaining treatment. American Bar Association, American Medical Association, and the National conference of commissioners on uniform state laws together have declared the statute, the Uniform Determination of Death Act (UDDA) affirmed: “an individual is dead who has
The UDDA is a statute, to address the societal problem created in the mid-twentieth century, due to the development of mechanical ventilation and other organ-sustaining technologies, to support permanently brain-injured individuals. The justification of the UDDA was to establish a uniform definition of death, determined by
In the executive summary update of task force recommendations, declare requisite for the diagnosis of brain death in children of two neurologic examinations is performed by two independent physicians and two apnea tests, both of which may be organized by the physician managing ventilator care [56, 57]. Examinations should follow an observation period of 24 hours for neonates less than 30 days old and 12 hours for older infants and children up to age 18. It is significant to note that there may be institutional variance in the way these criteria are interpreted, and pediatricians may adapt their brain death testing methods to take into account the age-related anatomical and physiological differences between neonates, infants, and children. Parents and other family members of children undergoing brain death testing may require close attention and additional support [58, 59]. The pediatric guidelines were updated in 2011 by the American Academy of Pediatrics. A recent study reveals widespread disparities in adherence to the guidelines nationwide. It is essential to follow a standardized process to ensure accuracy in the diagnosis and inconsistencies in diagnosis could lead to false-positive brain death determinations, which could erode the public trust in the ability of physicians to declare death [58, 59, 60].
In December 2008, the President’s council on bioethics published a white paper (controversies in the determination of death) in which the neurological standard was carefully reexamined [27]. The council built the insight in biological reality by appropriately describing the clinical and pathophysiological understanding of brain death, which offers substantial reassurance to the ultimate validity of the neurological standard. It effectively gives a new foundation to the justification for the neurological standard of death. The council strongly agreed that “
The council works was a historical decision that answers lot of
Whether a patient in the condition of total brain failure is actually dead and can it be said with sufficient certainty to ground a course of action as the mortal remains of a human being. To ascertain those, up to this time, two facts about the diagnosis of total brain failure have been taken to provide basic support for a declaration of death: first, that the body of a patient with
Another view of the neurological standard was also pointed within the council for certainty about the vital status of patients with total brain failure, the only rational and defensible conclusion of such patients are severely injured, but not yet dead. Hence, only the traditional signs of permanent cessation of heart and lung function should be used to declare a patient dead. Accordingly, medical interventions for patients with total brain failure should be withdrawn only after they have been judged to be
The understanding of medical futility [61, 62] has been developed in several papers by Edmund D. Pellegrino. Futility is the condition of a patient’s disease, which is beyond medical rescue, such as beyond the powers of medical technology to help. Clinical futility is present when any medical intervention is considered as ineffective, non-beneficial, and disproportionately burdensome for the patient. The clinical judgments of the futility of a given therapeutic intervention involve a rational balancing of three factors: efficacy of the given intervention, the purpose of which doctor alone can make; second, the advantage of that intervention, the patients and/or their surrogates can make; and third, the burdens of the intervention (cost, discomfort, pain, or inconvenience), jointly assessed by both physicians and patients and/or their surrogates. Adjusting the relationship among those three criteria is at the heart of prudent, precautionary, and proportionate action [27].
Lastly, the council members on bioethics had opined that the current neurological standard for declaring death, grounded in a careful diagnosis of total brain failure, is biologically and philosophically defensible. The council also concluded that,
The DDR has been secured for the ethical and social acceptability of organ transplantation protocols from their primitive days. This rule demands assurance of the death of the donor as the first step in any ethically legitimate transplantation protocol (other than those involving healthy, living donors). Additionally, the death of the patient must not be accelerated, nor end-of-life care made vulnerable in any way, to accommodate the transplantation protocols [27]. No protocol can demand ethical approval without trustiness to the present rule, in any ethically legitimate transplantation protocol (other than those involving healthy, living donors).
Relaxation of the DDR is a morally and ethically inappropriate and rationally specious way to deal with the uncertainties of the standard for the death of the donor. It leaves the options of the criteria for death to individual preference, amounting to the eventual abolition of any stable criteria for death. Numerous additional dangers are the use of assisted suicide to facilitate organ donation, legitimizing the utilization of patients in permanent vegetative states or of less-than-perfect infants as donors [27]. It exposes “undeclared” patients to “presumed” consent to donation [27, 62, 63].
Montreal forum was formed to address the global challenge in response to the request from various countries to “WHO and Transplantation Society” to provide guidance for leading practices and health policy in death determination by neurological and/or circulatory criteria. The guidelines would promote safe practices assuring the absence of diagnostic errors in death determination, safeguarding patients and health care professionals, upgrading public and professional confidence in the dead donation process along with strengthening the availability of organs obtained by ethically legitimate donation and procurement practices. The principles adopted by the forum for discussion were the safeguarding the interests of dying patients overrides facilitating deceased donation for transplantation; task restricted to a scientific, medical, and biological basis for death determination; the principle of the “dead donor rule” applied to deceased donation practices; use of available best scientific and medical evidence for decisions; guidelines and recommendations must have utility, applicability, and be workable in a wide range of global health care practice settings. The key issues of the forum considered death as a biological event with a focus on the physiological aspect of the dying process and death determination and respectfully recognized the impact of attending religious, ethical, legal, spiritual, philosophical, and cultural aspects of death [1].
Forum outcome of the review developed some
The forum came to a consensus on an operational (practical and concrete) definition of human death based on measurable and observable biomedical standards that “Death occurs when there is permanent loss of capacity for consciousness and irreversible loss of all brainstem functions.” This might result from permanent stoppage of circulation and/or after catastrophic brain injury. The “permanent” refers to loss of function that cannot resume automatically and will not be returned through intervention. Death is a single phenomenon founded on stoppage of brain function (loss of capacity for consciousness and brainstem reflexes) with two mechanisms to reach that point: permanent absence of circulation or subsequent to a catastrophic brain injury—two entrances, one exit. It is understood that the overwhelming majority of death determination in the world occurs after the stoppage of circulation and usually occurs external to health care settings. In some regions, the dead donation practices include re-establishing circulation (CPR, extracorporeal organ support) following death for the preservation of organs. Future research will enrich this issue for the clarity that constitutes re-establishing circulation, physiologically meaningful circulation, circulation versus oxygenation, and distinctions between organ targeted, regional, and whole-body circulation [1, 64].
During the 50 years since the publication of reports on the determination of death by neurologic criteria by Harvard University and the WMA (Sydney declaration) in 1968, brain death/death on neurological criteria (BD/DNC) protocols have been developed in many countries around the world. However, some countries still do not have medical standards for BD/DNC, and there is also international and intranational variability between the protocols that do exist [65, 66, 67, 68].
Discrepancies were noted in the studies by Wijdicks, Wahlster et al., and Chua et al. between protocols in this region in the criteria used for diagnosis of BD/DNC. Nonetheless, these studies were all limited reviews, though they addressed a number of examiners, observation time, the time between examinations, concordance/discordance with AAN—brain death/death by neurological criteria practice parameters, target value and methods of apnea testing, and requirement for ancillary testing. They did not explore the more distinct aspects of BD/DNC protocols, such as the technique used to rule out the effect of drugs on the evaluation, minimum temperature and blood pressure for an evaluation to be performed, a technique used to assess each component of the examination and findings of BD/DNC, preparation for rationale to discard apnea testing, accepted ancillary tests, need for communication with a person’s family, time of death, and stopping of organ support [68]. The existence of a protocol in a given country is dependent on acceptance of BD/DNC as death, access to resources (neurosciences/critical care experts), the presence of a transplant network, and local laws. Religious beliefs markedly influence the acceptance of BD/DNC as death. Although religious views in these countries are distinct from those in the rest of the world, the diversity of political, economic, legal, social, and religious climates throughout the region mirrors that globally [65, 66, 67, 68].
A review by Lewisa et al. in 2020 was published in a clinical neurology journal to find out the similarities and differences in the official protocols for the determination of death in Asia Pacific countries (57 of 197 UN) and concluded that protocols for conducting a BD/DNC determination vary markedly. In their report, only 24 of the 37 countries had brain death protocols (69%), but vary in definition such as whole-brain death and brain stem death; a number of examinations vary from single to double, separated by 6–48 hours; and the prerequisites, clinical examination, apnea testing procedure, and indications for/selection of ancillary tests varied. But agreed on that the damage to be irreversible or be permanent, all function/all activities are to be absent before declaring BD/DNC. Also, it is emphasized to harmonize protocols both within this region and worldwide [65, 66, 67, 68].
Traditionally, death occurs with the confirmation of irreversible cessation of cardiorespiratory function [3, 53, 54, 55, 56, 57, 58]. The use of artificial maintenance of life support and organ transplant leads to introduce a new criterion of death determination of permanently nonfunctioning brain, called irreversible coma equated to brain death. In recent years, however, controversy has arisen about the clinical and ethical validity of the neurological standard.
Source: Ref. [
AAN clinical criteria on the determination of brain death [53, 54, 55, 56] can be considered to consist of four steps: Prerequisites, Neurological assessment (coma, absence of brain stain reflex, apnea), Ancillary test, and Documentation.
Prerequisites for clinical criteria of brain death determination.
Establish permanent and predicted explanation of coma:
The explanation of coma is often establish by history, clinical examination, neuroimaging, and laboratory tests.
Rule out the existence of any CNS-depressant drug effect by history, drug screen, calculation of clearance; or, if available, drug plasma levels below the therapeutic range. Prior use of hypothermia (following CPR) may delay drug metabolism. The legitimate alcohol limit for driving (blood alcohol content 0.08%) is a practical threshold below which an examination to determine brain death could adequately proceed.
Should be no current administration or existence of neuromuscular blocking agents (train of four twitches with maximal ulnar nerve stimulation).
Should be no critical electrolyte, acid–base, or endocrine disorder (severe acidosis or laboratory values markedly deviated from the norm).
Ensure normal core temperature.
Raise the body temperature and to sustain a normal or near-normal temperature (36°C) use a warming blanket. To prevent delaying an increase in PaCO2, normal or near-normal core temperature is preferred during the apnea test.
Ensure normal systolic blood pressure. Hypotension or hypovolemia should be corrected by vasopressors or vasopressin. Neurologic examination is commonly reliable with a systolic blood pressure ≥ 100 mm Hg.
Perform neurologic examination (one neurological examination is enough to declare brain death in the USA). A certain period of time has to be passed since the onset of the brain insult to rule out the possibility of recovery (usually several hours). However, some US state statutes require two examinations.
Legally, all physicians are authorized to determine brain death in the USA. Neurologists, neurosurgeons, and intensive care specialists may have specialized expertise. It appears rational that all physicians making a determination of brain death be absolutely familiar with brain death criteria and have demonstrated competence in this complex examination.
Neurological assessment for clinical criteria for brain death determination.
Coma:
Profound loss of consciousness with no response to any stimuli. No evidence of responsiveness. No motor response on noxious stimuli other than spinally mediated reflexes.
Absence of brainstem reflexes:
Lack of pupillary response to bright light is produced in both eyes. Usually, pupils are fixed in a midsize or dilated position (4–9 mm). Constricted pupils signify the possibility of drug intoxication. A magnifying glass can be used in doubtful cases.
Oculocephalic testing and oculovestibular reflex testing: Absence of ocular movements. Once the integrity of the cervical spine is ensured, the head is briskly rotated horizontally and vertically. No movement of the eyes relative to head movement. The oculovestibular reflex is tested by irrigating each ear with ice water after the patency of the external auditory canal is confirmed. The head is elevated to 30°. Each external auditory canal is irrigated (one ear at a time) with approximately 50 ml of ice water. Eye movement was absent during 1 minute of observation. Both sides are tested, with an interval of several minutes.
Absence of corneal reflex: Touching the cornea with a piece of tissue paper, a cotton swab, or squirts of water, no eyelid movement will be demonstrated.
Absence of facial muscle movement to a noxious stimulus: Deep pressure on the supraorbital ridge and the condyles at temporomandibular joints produce no grimacing or facial muscle movement.
Lack of pharyngeal and tracheal reflexes. This reflex is tested after stimulation of the posterior pharynx with a tongue blade or suction device. The tracheal reflex is most reliably tested by examining the cough response to tracheal suctioning.
Apnea test:
Absence of a breathing drive is tested with a CO2 challenge. Usually, a rise in PaCO2 above normal levels is the typical practice but requires preparation before the test.
Prerequisites for apnea test: (1) Normotension, (2) Normothermia, (3) Euvolemia, (4) Eucapnia (PaCO2 35–45 mm Hg), (5) Lack of hypoxia, and (6) No prior evidence of CO2 retention (COPD, excessive obesity).
Procedure:
Ensure a systolic blood pressure ≥ 100 mm Hg, if needed by vasopressors.
It is mandatory to pre-oxygenate with 100% oxygen for at least 10 minutes to a PaO2 > 200 mm Hg.
Diminish frequency of ventilation to 10 breaths per minute to eucapnia.
Diminish positive end-expiratory pressure (PEEP) to 5 cm H2O (oxygen desaturation with decreasing PEEP suggest problems with apnea testing).
If pulse oximetry oxygen saturation persists >95%, obtain a baseline blood gas.
Detach the patient from the ventilator.
Maintain oxygenation (deliver 100% O2 at 6 L/min by endotracheal tube).
Observe closely for 8–10 minutes for respiratory movements. Respiration may be abdominal or may include a brief gasp.
Exclude if systolic blood pressure decreases to <90 mm Hg.
Exclude if oxygen saturation measured by pulse oximetry is <85% for 30 seconds.
If the respiratory drive is absent, repeat blood gas (PaO2, PaCO2, pH, bicarbonate, base excess) after approx. 8 minutes.
The apnea test is positive if respiratory movements are absent and arterial PCO2 is ≥60 mm Hg (supports the clinical diagnosis of brain death).
If the test is inconclusive but the patient is hemodynamically stable during the procedure, the test could be repeated for a longer period of time (10–15 minutes) after the patient is again adequately pre-oxygenated.
Supportive tests to diagnose brain death.
The ancillary tests such as EEG, cerebral angiography, nuclear scan, TCD, CTA, and MRI/MRA are at present used for adults in clinical practice. Three tests may be preferred such as EEG, nuclear scan, or cerebral angiogram, as the most hospital has the logistic to perform and interpret. The supportive tests can be done when there is no scope for apnea test or uncertainty exists. The ancillary tests are usually practiced to shorten the duration of the observation period. The interpretation of each of these tests requires expertise. In adults, ancillary tests are not needed for the clinical diagnosis of brain death and cannot replace a neurologic examination.
Documentation of the time of death.
The moment of brain death must be documented in medical records and is the time the arterial PCO2 reached the target value. But in patients where the apnea test is discarded, the time of death is when the ancillary test has been officially interpreted. A checklist is filled out, signed, and dated.
For the millennia, the human has fought with the concept and criteria of and the line between life and death continues to be debated. The profound changes caused by life-sustaining technology and transplantation continue to challenge our notions of life and death. The cardiopulmonary approach is an age-old practice for the determination of death that ensures social acceptance without any debate. The public is also used to rely on the somatic standard for criteria of death such as cooling of the body, absence of breath, loss of consciousness, rigor mortis, putrefaction, and so on.
Despite scientific progress in the last few decades, there remain big variations in the diagnosis criteria applied in each country with legal regulations resulting in misunderstandings among the public and health care professionals. However, the Harvard committee in 1968 develops a set of criteria of the permanently nonfunctioning brain, called irreversible coma equated to brain death. On the same date, the WMA declared a guideline for the determination of death known as the
The global philosophical, ethical, legal, and biomedical controversies of determining death due to life support, organ supports, and organ transplantation issues console us in the historic report published (1981) by President commission for the study of ethical problems in medicine and behavioral research,
WHO in 2014 published clinical criteria on the determination of death, mentioning various ways to determine death but there is only one way of being dead, so the two classic algorithms of brain death and circulatory death merge into a single endpoint identified as death and should not imply that brain death and circulatory death are two distinct phenomena [3]. They prepare a workable flowchart of cardiocirculatory algorithm and neurological algorithm to declare death. That guideline provides a minimum determination of death criteria to be acceptable for medical practice worldwide to achieve international consensus on clinical criteria to maintain public trust and promote ethical practices that respect fundamental rights of people and minimize philosophical, ethical, and biomedical debate in the human death. The WHO clinical criteria of 2014 did not mention the detail of clinical examination. Harvard report describes the clinical criteria and AAN guidelines on clinical criteria already accepted globally.
American Association of Neurology (AAN) in 2019 validated that brain death is the irreversible loss of all functions of the entire brain and is also equivalent to circulatory death. The testing methods of brain death take into account the age-related anatomical and physiological differences between neonates, infants, and children. Parents and other family members of children undergoing brain death testing may require close attention and additional support [58, 59].
International Guidelines for the Determination of Death—Phase I. Montreal Forum Report; 2012. Available from: http://www.who.int/patientsafety/montreal-forum-report.pdf
Clinical Criteria for the Determination of Death. Geneva: World Health Organization; 2017. Licence: CC BY-NC-SA 3.0 IGO
Controversies in the Determination of death: A white paper by the President Council on Bioethics (2008). Available from: http://hdl.handle.net/10822/559343
Evidence-based guideline update: Determining brain death in adults (Report of the Quality Standards Subcommittee of the American Academy of Neurology). Neurology 2010;74(23):1911–1918. DOI:10.1212/WNL.0b013e3181e242a8
All praise to Almighty to bless me with good health to complete this chapter. Acknowledge to all staff of the Forensic Medicine department of IMC and my family member for their sincere cooperation. Special thanks to Prof. Sharfuddin Ahmed, VC of BSMMU for encouraging me to complete. Also thanks to Dr. Ferdausi Rahman for her review of some portion of scripts.
The authors declare no conflict of interest.
Prof. Md Shah Alam developed the conception and design of the article and drafted the manuscript, providing important intellectual content.
Not applicable.
AAN | American Association of Neurology |
BD | brain death |
CNS | central nervous system |
CTA | computed tomography angiography |
CDD | controlled death donor |
COPD | chronic obstructive pulmonary disease |
DDR | death donor rule |
MRA | magnetic resonance angiogram |
PVS | persistent vegetative state |
TCD | transcranial Doppler |
CCA | cerebral circulatory arrest |
BSMMU | Bangabandhu Sheikh Mujib Medical University, Bangladesh |
DNC | death on neurological criteria |
UDDA | unifying determination of death act |
WHO | World Health Organization |
WMA | World Medical Association/World Medical Assembly |
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Kerrigan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8450",title:"Beta Thalassemia",subtitle:null,isOpenForSubmission:!1,hash:"976f72013cd8e78d8f65bfb1f51f0146",slug:"beta-thalassemia",bookSignature:"Marwa Zakaria and Tamer Hassan",coverURL:"https://cdn.intechopen.com/books/images_new/8450.jpg",editedByType:"Edited by",editors:[{id:"187545",title:"Prof.",name:"Marwa",middleName:null,surname:"Zakaria",slug:"marwa-zakaria",fullName:"Marwa Zakaria"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8316",title:"Normal and Malignant B-Cell",subtitle:null,isOpenForSubmission:!1,hash:"a12608fa8d5fdb33c956f967974a4ef1",slug:"normal-and-malignant-b-cell",bookSignature:"Mourad Aribi",coverURL:"https://cdn.intechopen.com/books/images_new/8316.jpg",editedByType:"Edited by",editors:[{id:"40046",title:"Prof.",name:"Mourad",middleName:null,surname:"Aribi",slug:"mourad-aribi",fullName:"Mourad Aribi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7181",title:"Erythrocyte",subtitle:null,isOpenForSubmission:!1,hash:"267d215004c995048557176978208b15",slug:"erythrocyte",bookSignature:"Anil Tombak",coverURL:"https://cdn.intechopen.com/books/images_new/7181.jpg",editedByType:"Edited by",editors:[{id:"202814",title:"Associate Prof.",name:"Anil",middleName:null,surname:"Tombak",slug:"anil-tombak",fullName:"Anil Tombak"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7874",title:"Germ Line Mutations Associated Leukemia",subtitle:null,isOpenForSubmission:!1,hash:"cb407bb000c66ebe6172b9dc3d6f9fb4",slug:"germ-line-mutations-associated-leukemia",bookSignature:"Zhan He Wu",coverURL:"https://cdn.intechopen.com/books/images_new/7874.jpg",editedByType:"Edited by",editors:[{id:"226446",title:"Dr.",name:"Zhan He",middleName:null,surname:"Wu",slug:"zhan-he-wu",fullName:"Zhan He Wu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6905",title:"Blood Groups",subtitle:null,isOpenForSubmission:!1,hash:"545ab2a5b402edec6332c7d632eba398",slug:"blood-groups",bookSignature:"Anil Tombak",coverURL:"https://cdn.intechopen.com/books/images_new/6905.jpg",editedByType:"Edited by",editors:[{id:"202814",title:"Associate Prof.",name:"Anil",middleName:null,surname:"Tombak",slug:"anil-tombak",fullName:"Anil Tombak"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7125",title:"Iron Deficiency Anemia",subtitle:null,isOpenForSubmission:!1,hash:"25d82a6ea6c9d80b195bb40aad06be49",slug:"iron-deficiency-anemia",bookSignature:"Luis Rodrigo",coverURL:"https://cdn.intechopen.com/books/images_new/7125.jpg",editedByType:"Edited by",editors:[{id:"73208",title:"Prof.",name:"Luis",middleName:null,surname:"Rodrigo",slug:"luis-rodrigo",fullName:"Luis Rodrigo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:40,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"39123",doi:"10.5772/50698",title:"Measurement Techniques for Red Blood Cell Deformability: Recent Advances",slug:"measurement-techniques-for-red-blood-cell-deformability-recent-advances",totalDownloads:7145,totalCrossrefCites:24,totalDimensionsCites:67,abstract:null,book:{id:"2607",slug:"blood-cell-an-overview-of-studies-in-hematology",title:"Blood Cell",fullTitle:"Blood Cell - An Overview of Studies in Hematology"},signatures:"Youngchan Kim, Kyoohyun Kim and YongKeun Park",authors:[{id:"143622",title:"Prof.",name:"YongKeun",middleName:null,surname:"Park",slug:"yongkeun-park",fullName:"YongKeun Park"},{id:"143623",title:"Mr.",name:"Kyoohyun",middleName:null,surname:"Kim",slug:"kyoohyun-kim",fullName:"Kyoohyun Kim"},{id:"143624",title:"Mr.",name:"Sangyeon",middleName:null,surname:"Cho",slug:"sangyeon-cho",fullName:"Sangyeon Cho"}]},{id:"31178",doi:"10.5772/38961",title:"Physiological Factors in the Interpretation of Equine Hematological Profile",slug:"haematological-profile-of-the-horse-phisiological-factors-influencing-equine-haematology",totalDownloads:10752,totalCrossrefCites:15,totalDimensionsCites:35,abstract:null,book:{id:"1830",slug:"hematology-science-and-practice",title:"Hematology",fullTitle:"Hematology - Science and Practice"},signatures:"K. Satué, A. Hernández and A. Muñoz",authors:[{id:"125292",title:"Dr.",name:"Katy",middleName:null,surname:"Satué Ambrojo",slug:"katy-satue-ambrojo",fullName:"Katy Satué Ambrojo"}]},{id:"55356",doi:"10.5772/intechopen.68617",title:"Neutrophils in Rheumatoid Arthritis: A Target for Discovering New Therapies Based on Natural Products",slug:"neutrophils-in-rheumatoid-arthritis-a-target-for-discovering-new-therapies-based-on-natural-products",totalDownloads:2059,totalCrossrefCites:9,totalDimensionsCites:12,abstract:"Rheumatoid arthritis (RA) is a systemic autoimmune disorder with an important inflammatory component in joints. Neutrophils are the most abundant leukocytes in inflamed joints, and play an essential role in the initiation and progression of RA. Neutrophil effector mechanisms include the release of proinflammatory cytokines, reactive oxygen and nitrogen species (ROS and RNS), and granules containing degradative enzymes, which can cause further damage to the tissue and amplify the neutrophil response. Therefore, the modulation of neutrophil migration and functions is a potential target for pharmacological intervention in arthritis. The pharmacologic treatment options for RA are diverse. The current treatments are mostly symptomatic and have side effects, high costs, and an increased risk of malignancies. Because of these limitations, there is a growing interest in the use of natural products as therapies or adjunct therapies. Herbal products have attracted considerable interest over the past decade because of their multiple beneficial effects such as their antioxidant, anti-inflammatory, antiproliferative, and immunomodulatory properties. This chapter focuses on the role of neutrophils in the pathogenesis of arthritis and the action of substances from natural products as putative antirheumatic therapies.",book:{id:"5834",slug:"role-of-neutrophils-in-disease-pathogenesis",title:"Role of Neutrophils in Disease Pathogenesis",fullTitle:"Role of Neutrophils in Disease Pathogenesis"},signatures:"Elaine Cruz Rosas, Luana Barbosa Correa and Maria das Graças\nHenriques",authors:[{id:"64332",title:"Dr.",name:"Maria Das Graças",middleName:null,surname:"Henriques",slug:"maria-das-gracas-henriques",fullName:"Maria Das Graças Henriques"},{id:"197932",title:"Dr.",name:"Elaine",middleName:"Cruz",surname:"Rosas",slug:"elaine-rosas",fullName:"Elaine Rosas"},{id:"199677",title:"MSc.",name:"Luana",middleName:null,surname:"Correa",slug:"luana-correa",fullName:"Luana Correa"}]},{id:"46041",doi:"10.5772/57335",title:"An Insight into the Abnormal Fibrin Clots — Its Pathophysiological Roles",slug:"an-insight-into-the-abnormal-fibrin-clots-its-pathophysiological-roles",totalDownloads:3896,totalCrossrefCites:4,totalDimensionsCites:11,abstract:null,book:{id:"3836",slug:"fibrinolysis-and-thrombolysis",title:"Fibrinolysis and Thrombolysis",fullTitle:"Fibrinolysis and Thrombolysis"},signatures:"Payel Bhattacharjee and Debasish Bhattacharyya",authors:[{id:"88185",title:"Prof.",name:"Debasish",middleName:null,surname:"Bhattacharyya",slug:"debasish-bhattacharyya",fullName:"Debasish Bhattacharyya"},{id:"170045",title:"Ms.",name:"Payel",middleName:null,surname:"Bhattacharjee",slug:"payel-bhattacharjee",fullName:"Payel Bhattacharjee"}]},{id:"39110",doi:"10.5772/48250",title:"Laboratory Reference Intervals in Africa",slug:"laboratory-reference-intervals-in-africa",totalDownloads:4494,totalCrossrefCites:0,totalDimensionsCites:10,abstract:null,book:{id:"2607",slug:"blood-cell-an-overview-of-studies-in-hematology",title:"Blood Cell",fullTitle:"Blood Cell - An Overview of Studies in Hematology"},signatures:"Clement E. Zeh, Collins O. Odhiambo and Lisa A. Mills",authors:[{id:"141066",title:"Dr",name:"Clement",middleName:null,surname:"Zeh",slug:"clement-zeh",fullName:"Clement Zeh"}]}],mostDownloadedChaptersLast30Days:[{id:"66797",title:"Blood Transfusion Reactions",slug:"blood-transfusion-reactions",totalDownloads:2617,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Blood transfusion reaction/adverse transfusion reactions could be fatal/severe or mild, immediate or delayed, immunological or nonimmunological, and infectious or noninfectious, and attention is paid particularly to the incidence, possible causes and pathophysiology, clinical features, and management of each type with the aim of improving awareness and raising consciousness towards improving blood safety and judicious use of blood so as to forestall these blood transfusion reactions as much as possible. This chapter serves as a synopsis to adverse blood reactions, which are very common but apparently more often under-recognized and/or under-reported particularly in developing countries. This should sharpen the consciousness of all health practitioners involved in blood transfusion services towards taking measures at preventing transfusion reactions right from donor selection up to the infusion of blood into the recipients.",book:{id:"6905",slug:"blood-groups",title:"Blood Groups",fullTitle:"Blood Groups"},signatures:"John Ayodele Olaniyi",authors:[{id:"202764",title:"Dr.",name:"John",middleName:null,surname:"Olaniyi",slug:"john-olaniyi",fullName:"John Olaniyi"}]},{id:"49387",title:"Thalassemia — From Genotype to Phenotype",slug:"thalassemia-from-genotype-to-phenotype",totalDownloads:4877,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Thalassemia encompasses serious diseases with complex pathophysiology that is difficult to explain since it is considered a group of defects with similar clinical effects, still not a single disorder.",book:{id:"4729",slug:"inherited-hemoglobin-disorders",title:"Inherited Hemoglobin Disorders",fullTitle:"Inherited Hemoglobin Disorders"},signatures:"Ghada Y. El-Kamah and Khalda S. Amr",authors:[{id:"58735",title:"Prof.",name:"Ghada",middleName:null,surname:"El-Kamah",slug:"ghada-el-kamah",fullName:"Ghada El-Kamah"},{id:"176872",title:"Prof.",name:"Khalda",middleName:null,surname:"Amr",slug:"khalda-amr",fullName:"Khalda Amr"}]},{id:"51831",title:"Disorders Mimicking Myelodysplastic Syndrome and Difficulties in its Diagnosis",slug:"disorders-mimicking-myelodysplastic-syndrome-and-difficulties-in-its-diagnosis",totalDownloads:4511,totalCrossrefCites:1,totalDimensionsCites:6,abstract:"Myelodysplastic morphology of blood cells can be encountered not only in myelodysplastic syndrome (MDS) but also in nonclonal disorders like viral, bacterial, parasitic infections, juvenile rheumatoid arthritis, polyarteritis nodosa, immune thrombocytopenic purpura (ITP), iron deficiency anemia, megaloblastic anemia, dysgranulopoietic neutropenia, congenital neutropenia, cases with microdeletion 22q11.2, malignant lymphoma, after administration of granulocyte colony stimulating factor, chemotherapy, steroids, smoking, alcohol, posttransplantation, copper deficiency also, together with or without cytopenia. Absence of cytogenetic abnormality in 50–70% of cases with MDS, some overlapping morphological and/or pathophysiological features make it challenging to differentiate between MDS and other diseases/disorders like aplastic anemia, refractory ITP, copper deficiency. Transient genetic abnormalities including monosomy 7 in megaloblastic anemia; increased immature myeloid cells in bone marrow of cases with copper, vitamin B12, or folic acid deficiency in the setting of cytopenia and dysmorphism may also lead to the misdiagnosis of MDS. On the other hand, there are also cases of transient MDS. In this chapter, a literature is be presented to draw attention of the readers on the disorders that mimic MDS. Additionally, our personal experiences are also be shared. Awareness of disorders mimicking MDS may prevent over- or underdiagnosis of MDS.",book:{id:"5276",slug:"myelodysplastic-syndromes",title:"Myelodysplastic Syndromes",fullTitle:"Myelodysplastic Syndromes"},signatures:"Lale Olcay and Sevgi Yetgin",authors:[{id:"184156",title:"Prof.",name:"Lale",middleName:null,surname:"Olcay",slug:"lale-olcay",fullName:"Lale Olcay"}]},{id:"64871",title:"Diagnosis and Classification of Myelodysplastic Syndrome",slug:"diagnosis-and-classification-of-myelodysplastic-syndrome",totalDownloads:3212,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disorder characterized by morphological dysplastic changes in one or more of the major hematopoietic cell lines. MDS can present with varying degrees of single or multiple cytopenias including neutropenia, anemia and thrombocytopenia. Presentation of MDS can range from asymptomatic to life threatening. MDS diagnosis and classification present important challenges, particularly in the distinction from benign conditions. French-American-British (FAB) classification proposed a classification based on easily obtainable laboratory information and was recommended in early and as modified by guidelines of new classification of World Health Organization (WHO). The strategy of diagnostic laboratory in MDS depends on morphological changes and is based on existence of dysplastic changes in the peripheral blood and bone marrow including peripheral blood smear, bone marrow aspirate smear and bone marrow trephine biopsy. The correct morphological interpretation and the use of cytogenetics, immunophenotyping, immunohistochemistry and molecular analysis will give valuable information on diagnosis and prognosis.",book:{id:"7138",slug:"recent-developments-in-myelodysplastic-syndromes",title:"Recent Developments in Myelodysplastic Syndromes",fullTitle:"Recent Developments in Myelodysplastic Syndromes"},signatures:"Gamal Abdul Hamid, Abdul Wahab Al-Nehmi and Safa Shukry",authors:[{id:"36487",title:"Prof.",name:"Gamal",middleName:null,surname:"Abdul Hamid",slug:"gamal-abdul-hamid",fullName:"Gamal Abdul Hamid"},{id:"273724",title:"Dr.",name:"Safa",middleName:null,surname:"Shukry",slug:"safa-shukry",fullName:"Safa Shukry"},{id:"277511",title:"Dr.",name:"Abdulwahab",middleName:null,surname:"Al-Nehmi",slug:"abdulwahab-al-nehmi",fullName:"Abdulwahab Al-Nehmi"}]},{id:"70780",title:"Laboratory Diagnosis of β-Thalassemia and HbE",slug:"laboratory-diagnosis-of-thalassemia-and-hbe",totalDownloads:1400,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"β-Thalassemia and HbE, each, is a syndrome resulted from quantitative and qualitative defects of β-globin chain, respectively. In addition to history retrieve and physical examination, diagnosis of these disorders requires laboratory information. Laboratory tests that are conventionally performed to diagnose the β-thalassemia and HbE are classified into two groups, based on the purposes, including the screening tests and confirmatory tests. The screening tests are aimed to screen for carriers of the β-thalassemia and HbE, while confirmatory tests are the tests performed to definitely diagnose these disorders. This chapter will explain all of these tests, the information of which will be useful for those who are working and interested in the β-thalassemia and HbE.",book:{id:"8450",slug:"beta-thalassemia",title:"Beta Thalassemia",fullTitle:"Beta Thalassemia"},signatures:"Thanusak Tatu",authors:null}],onlineFirstChaptersFilter:{topicId:"183",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82161",title:"Blood Groups More than Inheritance of Antigenic Substances: Susceptibility to Some Diseases",slug:"blood-groups-more-than-inheritance-of-antigenic-substances-susceptibility-to-some-diseases",totalDownloads:9,totalDimensionsCites:0,doi:"10.5772/intechopen.104593",abstract:"Blood group antigens represent polymorphic traits inherited among individuals and populations. The objective of this chapter is to review articles that have reported; the association between blood group antigens and susceptibility to some diseases. Findings showed that O blood group had a greater frequency of severe infections such as E coli, cholera and blood group A was associated with incidence of smallpox and some bacterial infections. These are principally based on presence or absence of “H-like” and “A and B-like” antigens markers. Antigens A, B and H are connected to N-glycans of vWF and reduces the half-life of the protein (10 hours) for group O while non-O groups, 25 hours. The loss of A, B, and H antigens as malignancy progresses was linked to potential metastasis. Similarly, some tumors have A or A-like antigens this explains the propensity of group A to develop tumors. Blood type incompatibility between mother and foetus sensitizes the mother to develop alloantibodies that could potentially cause death of the foetus in utero, a condition known hydrops. Reviewed articles have reported close link between blood group antigens and susceptibility diseases. More studies are required to rationalize the mechanism associated to this.",book:{id:"10728",title:"Blood Groups - More Than Inheritance of Antigenic Substances",coverURL:"https://cdn.intechopen.com/books/images_new/10728.jpg"},signatures:"Williams Bitty Azachi and Kuschak Mathias Dakop"},{id:"80344",title:"RH Groups",slug:"rh-groups",totalDownloads:25,totalDimensionsCites:0,doi:"10.5772/intechopen.102421",abstract:"In 1939, a mother gave birth to a stillborn baby and underwent blood transfusion with ABO-matched blood from her husband. This resulted in a hemolytic transfusion reaction (HTR). Levine and Stetson postulated that a novel antigen was present in the baby and father, which was absent in the mother. Therefore, the mother’s immune system recognized this antigen and produced antibodies against it. This condition has been known as the hemolytic disease of the newborn for a long period of time. Since the antenatal management of the fetus has been developed, the term has been modified to hemolytic disease of the fetus and newborn (HDFN). This case led to the discovery of the antibody against the first antigen of the RH blood group system, the D antigen. To date, 56 antigens have been recognized within the RH blood group system. The five main antigens are D, C, c, E, and e. As observed in the above-mentioned case, the antibodies against these antigens are implicated in HTR and HDFN.",book:{id:"10728",title:"Blood Groups - More Than Inheritance of Antigenic Substances",coverURL:"https://cdn.intechopen.com/books/images_new/10728.jpg"},signatures:"Amr J. Halawani"},{id:"80254",title:"Neutrophil-Specific Antigens: Immunobiology, Genetics and Roles in Clinical Disorders",slug:"neutrophil-specific-antigens-immunobiology-genetics-and-roles-in-clinical-disorders",totalDownloads:36,totalDimensionsCites:0,doi:"10.5772/intechopen.102431",abstract:"Neutrophils are the most abundant nucleated cells in blood circulation and play important roles in the innate and adaptive immune responses. Neutrophil-specific antigens, only expressed on neutrophils, are glycoproteins originally identified in studies on neonatal neutropenia due to fetal-maternal incompatibility and autoimmune neutropenia of infancy. The most investigated neutrophil–specific antigens are the NA and NB antigens that their incompatibilities also cause transfusion-induced febrile reactions and acute lung injury, a potentially fatal reaction, and in bone marrow transplantation, causing graft rejection. NA antigens are members of the immunoglobulin superfamily and are low-affinity Fc-receptors FcγRIIIb (CD16b). Fc receptors connect the F(ab), the antigen-binding fragment of the antibody molecules, to neutrophils and lead them to recognize and phagocytize the targeted antigens. The NB (CD177) antigen belongs to the urokinase-type Plasminogen Activator Receptor Superfamily (uPAR, CD59, Ly6), but its specific functions have not been fully determined. It is known, however, that NB antigen binds proteinase-3 (PR3 to the neutrophil membrane), a serine protease. In clinical studies, it was also demonstrated that NB expression is highly elevated in Polycythemia Vera and is unexpectedly expressed in some cancer tissues. Neutrophil-specific antigens are examples of antigens that have important biological and clinical activities beyond antigenicity.",book:{id:"10728",title:"Blood Groups - More Than Inheritance of Antigenic Substances",coverURL:"https://cdn.intechopen.com/books/images_new/10728.jpg"},signatures:"Parviz Lalezari and Behnaz Bayat"},{id:"80716",title:"The ABO Blood Group System and Plasmodium falciparum (Pf ) Infection in Three Ethnic Groups Living in the Stable and Seasonal Malaria Transmission Areas of Burkina Faso (BF)",slug:"the-abo-blood-group-system-and-plasmodium-falciparum-pf-infection-in-three-ethnic-groups-living-in-t",totalDownloads:92,totalDimensionsCites:0,doi:"10.5772/intechopen.102475",abstract:"Genetic factors, including red blood cell polymorphisms, influence the severity of disease due to infection with Plasmodium falciparum (Pf). Studies show that these genetic factors associated with malaria susceptibility or resistance vary geographically, ethnically, and racially. We performed cross-sectional surveys in population living in rural villages from three ethnic groups. The blood group (BG) was determined genetically using two polymorphisms (rs8176719 and rs8176746). Out of 548 participants, 29.7% were Mossi, 38.2% were Fulani, and 32.1% were Rimaibe. The distribution of BG was, respectively, A: 25.5%, B: 26.6%, AB: 7.3%, and O: 40.5%. BG O was not only the common blood type overall, but was higher in Fulani (52.6%) than others. Fulani was associated with a reduced risk of infection and lower parasite densities than sympatric populations. The subjects with non-O blood were less susceptible to malaria infection. An association between ethnicity and malaria infection during the high transmission season as well as an association between the non-O blood group and malaria infections according to ethnicity was found. This was also true when ethnic groups were considered separately. Our results have demonstrated that the Fulani are not only less susceptible to Pf malaria infection, but when infected have lower parasite densities. Individuals with non-O blood are at lower risk of infection.",book:{id:"10728",title:"Blood Groups - More Than Inheritance of Antigenic Substances",coverURL:"https://cdn.intechopen.com/books/images_new/10728.jpg"},signatures:"Edith Christiane Bougouma, Alphonse Ouedraogo and Sodiomon Bienvenu Sirima"},{id:"80474",title:"ABO Blood Group and Thromboembolic Diseases",slug:"abo-blood-group-and-thromboembolic-diseases",totalDownloads:42,totalDimensionsCites:0,doi:"10.5772/intechopen.102757",abstract:"Thromboembolic diseases are usually inherited in the family. The tendency to repeat in an individual is a phenomenon that allows it to be studied. The inheritance and recurrence of thromboembolic diseases, of course, have individual risk factors for this occurrence. In the past, the ABO blood group was only needed for transfusion and organ transplant therapy. Over time, scientists think that blood type is a risk factor for certain diseases, including thromboembolism. Many studies divide between type O and non-O blood groups, both of which are distinguished by the presence of antigens on the cell surface and antibodies in the plasma of individuals. Type O does not have A, B antigens but has antibodies against A, B antigens, and vice versa for the non-O type. Many studies have shown that the non-O blood group has a risk factor for thromboembolic diseases, commonly due to higher levels of von Willebrand factor (VWF) and factor VIII (FVIII). These thromboembolic events can occur in arteries or venous. Thromboembolic manifestations are often associated with cardiovascular diseases for arterial thrombosis; and deep vein thrombosis (DVT) and pulmonary embolism (PE) for venous thromboembolism (VTE).",book:{id:"10728",title:"Blood Groups - More Than Inheritance of Antigenic Substances",coverURL:"https://cdn.intechopen.com/books/images_new/10728.jpg"},signatures:"Yetti Hernaningsih"},{id:"78997",title:"ABO Blood Groups and Risk of Glioma",slug:"abo-blood-groups-and-risk-of-glioma",totalDownloads:60,totalDimensionsCites:0,doi:"10.5772/intechopen.100566",abstract:"Gliomas are one of the most common primary brain tumors and the etiology of gliomas remains unknown in most cases. The aim of this case–control study was to investigate possible association between incidence in relation to glioma and certain blood groups. This study included 100 histopathologically verified cases of glioma and 200 age and sex-matched controls without malignant diseases that were admitted to the same hospital. The results revealed that the patients with group AB were at 3.5-fold increased risk of developing glioma compared to the patients with other ABO blood groups. In this particular study, there was more male patients with glioma with the blood group AB. However, mechanisms that explain the relationship between the blood groups ABO and a cancer risk are unclear. Several hypotheses have been proposed, including the one with a modulatory role of blood group ABO antigens. In addition, the blood group ABO system regulates the level of circulating proinflammatory and adhesion molecules which play a significant role in the tumorigenesis process. Additionally, the recent discovery that includes the von Willebrand factor (vWF) as an important modulator of angiogenesis and apoptosis provides one plausible explanation as regards the role of the blood group ABO in the tumorigenesis process. To our knowledge, this is the first study that examined the relationship of blood group in patients diagnosed with glioma among the Serbian population. Moreover, for the first time our study results suggested that blood group AB increased the risk of glioma. The results of this study suggested that the blood group AB could be one of hereditary factors which had an influence on the occurrence of glioma. 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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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