miRNA and mRNA targets selected under study.
\r\n\tThis book will address the various modern, technical, and practical aspects of smart technology for capturing solar radiation and converting it into different forms of energy, as well as enabling it for renewables integration in energy generation and transformation, built environment, transportation, buildings, and agriculture.
\r\n\r\n\tThe book will cover the most recent developments, innovations and applications concerning the following topics:
\r\n\t• Solar radiation – Smart and enabling technologies for measurement, modelling, and forecasting
\r\n\tHigh-resolution measurement sensor and instrument technology (Pyranometers, Albedometers, Pyrheliometers, UV Radiometers, Sun Trackers, Spectroradiometer, Pyrgeometers, etc.), Artificial intelligence techniques for modelling and forecasting of solar radiation, Solar Irradiance forecast with satellite data, Solar potential analysis, Short-term forecasting of photovoltaic power and solar irradiance prediction with sky imagers.
\r\n\t• Renewable energy integration – Smart solutions for integration of RE in distributed generation, energy storage, and demand-side management.
\r\n\tIntegrated Photovoltaics: Smart technology for vehicle-integrated PV, Building Integrated PV, Agrivoltaics, Road-Integrated PV, Floating PV, Product-integrated PV.
\r\n\tRenewable Energy Applications in Built Environment and mobility: Solar cars, solar-powered electric charging stations, passive solar systems, solar heating, and cooling systems, building-integrated vegetation, multifunctional solar systems, solar pumps, solar lighting, solar shading, Natural lighting, Solar dryer, Greenhouse.
MicroRNAs (miRNAs) form a class of endogenously expressed small, non-coding RNAs, that play key roles in the regulation of gene expression of a broad spectrum of biological processes. However, in the field of toxinology, a science of naturally occurring toxins, the relationship between toxicity and microRNA expression is poorly understood. Microcystins (MCs) are potent cyclic peptide hepatotoxins produced by cyanobacteria, which pose a serious threat to aquatic organisms and may also affect human health through the consumption of contaminated waters or food. Although a number of cell physiologic pathways, potential targets for miRNA regulation, are implicated in the response to MCs in animals, no research so far investigated the role for miRNA genes in the mechanism of microcystin (MC)-induced toxicity in fish. The chapter aims to summarize recent achievements of our team in the field, focusing on expression profiling
MicroRNAs (miRNAs) form a class of endogenously expressed small, non-coding RNAs, that play key roles in the regulation of gene expression of a broad spectrum of biological processes. Figure 1 summarizes crucial steps in microRNA processing. MiRNAs are transcribed by RNA polymerases II or III as primary transcripts (pri-miRNAs), which are further processed by the nuclear RNase III enzyme Drosha to stem-loop-structured miRNA precursor molecules (pre-miRNAs). The pre-miRNAs are subsequently transported to the cytoplasm where the RNase III enzyme Dicer cleaves off the double stranded (ds) portion of the hairpin and generates a short-lived dsRNA of about 19–23 nucleotides (nt) in size. The duplex is subsequently unwound and only one strand gives rise to the mature miRNA, which is incorporated into miRNA-protein complexes (miRNPs) [1-2]. The mature miRNAs binds to partially complementary recognition sequences located in the 3\'-untranslated regions (3\'-UTRs) of mRNAs and target them for degradation or translational repression (reviewed in [3]).
miRNA processing and target recognition. The pri-miRNA is processed by the Drosha enzyme to a stem-loop-structured miRNA precursor molecule (pre-miRNA). The pre-miRNAs is transported to the cytoplasm where the Dicer enzyme cleaves off the double stranded (ds) portion of the hairpin and generates the mature miRNA, which is incorporated into miRNA-protein complexes (miRNPs). The mature miRNA binds to partially complementary recognition sequences on 3\'-UTRs of mRNAs and targets them for decay or translational repression.
In metazoans miRNA complementarity to their targets is far from perfect, so one miRNA can bind up to 200 targets, and each mRNA could have recognition sites for more than one miRNA. It is estimated that about 30% of the human protein-coding genes are negatively regulated by miRNA, which suggests that miRNAs are very important regulators of gene expression process [3]. Although specific functions and target mRNAs have been assigned to only a few dozen of miRNAs, much experimental evidence suggests that miRNAs participate in the regulation of a vast spectrum of biological processes. miRNAs control diverse cellular processes including animal development and growth, cell differentiation, signal transduction, cancer, neuronal disease, virus-induced immune defense, programmed cell death, insulin secretion, and metabolism (see [4] and references therein). Understanding of RNA interference (RNA
To discover aberrantly expressed miRNAs in fish and to determine how altered miRNA function contributes to a disease, new RNA
Studying fish miRNAs. MicroRNA discovery has been recently revolutionized by next-generation sequencing. Following ligation of specific linkers to small RNAs (which comprise miRNAs), cDNAs can be produced, which are ideally suited to sequencing using short-read platforms. Databases now offer online catalogues of known microRNAs, which may further be examined for their pathways and functions through a variety of approaches, such as target functional analysis of candidate miRNAs using luciferase reporter assays and miRNA profiling with Real Time PCR.
As miRNAs regulate many different pathways and orchestrate integrated responses in cells and tissues, it is reasonable to think that they also play key roles in coordinating networks in the poisoned organs. Indeed, there are reports concluding that miRNAs may be key molecules involved in aberrant gene expression in liver cells exposed to hepatotoxic agents, other than MC-LR. For example, Fukushima and co-workers [8] have shown that two well known hepatotoxicants which induce hepatocellular injuries and necrosis, acetaminophen or carbon tetrachloride, were capable of modulating expression of two miRNAs (miR-298 and miR-370) in rats, and that those effects were accompanied by impaired liver metabolism. The observation that miRNAs levels in rat livers were changed by hepatotoxic compounds prompted our team to investigate the role of fish microRNAs in the context of liver-specific MC-LR toxicity.
Microcystins (MCs) are potent hepatotoxins produced by cyanobacteria of the genera
MCs have strong affinity to serine/threonine specific protein phosphatases (PP1 and PP2A), thereby acting as inhibitors of the enzymes [13]. The acute toxicity of MC can be explained by the PP inhibition, which leads to an excessive phosphorylation of cell proteins, to alterations in the cytoskeleton, and a loss of cell shape [14]. Another biochemical feature of MC toxicity is the production of reactive oxygen species (ROS). MC-related ROS generation has been reported using both
In recent years, new insights on the key molecules involved in the signal-transduction and toxicity have been reported [24], which highlighted the complexity of the interaction of these toxins with animal cells (Figure 3). Key proteins involved in MC up-take, biotransformation and excretion have been identified, demonstrating the ability of aquatic animals to metabolize and excrete the toxin. After having caused damage to intestinal (or gill) cells these toxins penetrate liver cell membranes through a bile acid carrier. In liver cells MCs inhibit serine/threonine-specific protein phosphatases, PP1 and PP2A, through the binding to them, thus perturbing signaling pathway controlled by the enzymes. The consequences are induction of mitochondrial permeability and loss of mitochondrial membrane potential leading to dysfunction of the mitochondria, induction of reactive oxygen species (ROS), DNA damage (through lowered expression of DNA-PK), and cell apoptosis (through increase Ca2+ levels, CaMKII). MC activity leads to the differential expression/activity of transcriptional factors (e.g. c-myc, p53) and protein kinases (NeK2) involved in the pathways of cellular differentiation, proliferation, tumor promotion activity, and metastasis [25].
Suggested pathways of MC up-take, toxicity, biotransformation and excretion in vertebrates. Based on the current knowledge, microRNAs (e.g. let-7 or miR-34a) may play roles in MC-LR dependent cell proliferation, cell-cycle arrest or apoptosis.
In the field of toxinology, a science of naturally occurring toxins, the relationship between toxicity and microRNA expression is poorly understood. However, based on current knowledge about genes involved in the animal cell response on the exposure to environmental stressors, putative targets for miRNA regulation emerge. Genes of transcription factors,
In the other pathway (Figure 3), mitogen-activated protein kinases (MAPKs) regulate the expression of proto-oncogenes which on the other hand regulate the transcription of genes involved in the growth and differentiation [29]. Expression of MAPKs is mediated by PP2A and are likely to be regulated by MC. The expression of three proto-oncogenes c-fos, c-jun and c-myc were reported to increase in liver, kidney and testis of Wistar rats injected intravenously with MC-LR, with higher levels registered in liver [30]. Expression of these genes suggest that a possible mechanism for the tumor-promoting activity of the toxin could be controlled by MAPKs. Importantly, c-MYC controls expression of let-7 miRNA members by binding to their promoters. The levels of let-7 have been reported to decrease in models of MYC-mediated tumorigenesis, and to increase when MYC is inhibited by chemicals [31]. It is also found that MYC can repress p21Cip1 transcription (Figure 1), thereby overriding a p21-mediated cell cycle checkpoint [32].
In 2008, we began a study of MC-LR induced transcriptional changes in European whitefish,
Whereas, the above study confirms that MC-LR exposure underlies various acute and chronic effects in fish, it is still little known about aberrant gene expression profiles and molecular pathways involved in the liver of MC-LR challenged organisms. Therefore, to improve our knowledge about adverse effects of MC-LR on hepatocyte cell responses in fish, we performed an initial microRNA study to examine the abundance of 9 selected miRNAs (omy-miR-21, omy-miR-21t, omy-miR-122, omy-miR-125a, omy-miR-125b, omy-miR-125t, omy-miR-199-5a, omy-miR-295, omy-let-7a), in liver samples of whitefish exposed for 24 or 48h to MC-LR at a dose of 100μg/kg body weight [4]. Interestingly, the study showed that MC-LR treatment affected expression levels of two miRNAs, omy-miR-125a (up-regulation) and omy-let-7a (down-regulation) [4].
Following the early demonstration that MC-LR modulates expression of let-7a and miR-125a, in our most recent work [33] we aimed at profiling expression of other 6 miRNAs and 8 mRNAs (Table 1) in the liver of challenged whitefish during the first 48 h after single intraperitoneal injection. From studies on mammals we chose miRNAs which play regulatory roles in pathways of signal transduction (let-7c, [34]; miR-9b, [35]), apoptosis and cell cycle (miR-16a, [36]; miR-21a, [37]; miR-34a, [7]) and fatty-acid metabolism (miR-122, which is a liver specific miRNA, [38]). The selection of mRNA targets (Table 1) was based on their reported aberrant tissue expression on exposure to environmental stressors, and included mRNAs involved in apoptosis and cell cycle (bax, [20]; cas6, cdkn1a, p53, [27]), signal transduction (p-ras, [39]), cellular iron homeostasis (frih, [40]), gene silencing by miRNAs (dcr, [41]), and nucleosome assembly (h2a, [4]). Together with the RNA expression, we analyzed levels of tumor suppressor protein p53 to assess its potential contribution in molecular mechanisms of liver toxicity induced by MCs in fish.
miRNA | \n\t\t\tPutative biological process* | \n\t\t
omy-let-7c | \n\t\t\tsignal transduction | \n\t\t
omy-miR-9b | \n\t\t\tsignal transduction | \n\t\t
omy-miR-16a | \n\t\t\tapoptosis, cell cycle | \n\t\t
omy-miR-21a | \n\t\t\tapoptosis, cell cycle | \n\t\t
dre-miR-34** | \n\t\t\tcell cycle, signal transduction | \n\t\t
omy-miR-122 | \n\t\t\tfatty-acid metabolism, maintenance of adult liver phenotype | \n\t\t
mRNA [gene abbreviation] | \n\t\t\tBiological process*** | \n\t\t
bcl2-associated X protein (bax) | \n\t\t\tapoptosis | \n\t\t
caspase 6 (cas6) | \n\t\t\tapoptosis | \n\t\t
cyclin-dependent kinase inhibitor 1a (cdkn1a) | \n\t\t\tcell cycle | \n\t\t
dicer (dcr) | \n\t\t\tgene silencing by miRNA | \n\t\t
ferritin heavy chain (frih) | \n\t\t\tcellular iron ion homeostasis | \n\t\t
histone 2A (h2a) | \n\t\t\tnucleosome assembly | \n\t\t
tumor protein 53 (p53) | \n\t\t\tapoptosis, cell cycle, signal transduction | \n\t\t
HNK Ras –like protein (p-ras) | \n\t\t\tsignal transduction | \n\t\t
miRNA and mRNA targets selected under study.
* based on literature review; see text for details.
** putative
*** in terms of Gene Ontology Annotation (http://www.ebi.ac.uk/QuickGO).
Quantifying miRNAs in different tissues is an important initial step in investigating their biological functions. To this end, we determined the expression levels of 6 selected miRNAs in adult whitefish liver using Real-Time qPCR. Prominent expression of miR-122 in the liver of whitefish was observed which is consistent with other data from fish [4,6] and mammals [42]. Variable expression levels of other miRNAs studied in the liver of whitefish corroborated results of previous work on normal human tissues [43], and they are also in agreement with available data on the fish miRNome isolated from rainbow trout [6] and zebrafish [44] miRNA libraries. While the actual expression values of miRNAs can vary by orders of magnitude between whitefish and humans [43], their relative abundance in a particular tissue should tend to be more conserved in evolution. Indeed, the order of individual miRNA abundances in human liver (miR-122 > let-7c ≈ miR-21 ≈ miR16 > miR-34a > miR-9; [43]) held in whitefish as well [33].
Our treatment study [33] identified miRNAs whose expression levels rose (from 2.7-fold for miR-122 to 6.8-fold for let-7c) in MC-LR treated fish, compared to the respective levels in control fish (Figure 4). The increase, which was most apparent at 24 h of the experiment, was correlated with a reduction in the expression of mRNAs: ferritin H (frih) and HNK Ras –like protein (p-ras) and an overexpression of bcl2-associated X protein (bax), cyclin dependent kinase inhibitor 1a (cdkn1a), dicer (dcr), histone 2A (h2a) and p53. Expression of the remaining caspase 6 (cas6) mRNA did not change over 48 h of the treatment. Moreover, exposure to MC-LR did not alter whitefish p53 protein levels [33].
Heat map and hierarchical clustering of differentially expressed genes and miRNAs in MC-LR treated whitefish. Each row represents one gene/miRNA and each column represents a mean of 5 replicates/duration of exposure. Colors represent expression levels of each individual gene/miRNA: red, up-regulation; green, down-regulation. Four distinct clusters (A through D) based on the observed expression profiles could be identified by the analysis. The analysis and visualization were performed using GenEx 5 software (MultiD Analyses AB; Sweden), based on raw expression data from our recent study [
The experiment allows one to determine which miRNAs change expression as a group or as a cluster. Genes that function together may define regulatory networks and regulate a common set of regulated genes. Using clustering software, we divided the significantly regulated miRNAs into different groups. In Figure 4 there were four different types of expression profiles among the miRNAs and genes. Some groups showed transient changes in the expression profile (clusters B and C) while others stably increase (cluster A) or decrease (cluster D) during the treatment with MC-LR. Bearing in mind a variety of likely silencing targets for, and the onset of, the aberrant miRNAs expression (Table 2; [33]) it may be concluded that they are involved in diverse molecular pathways, such as liver cell metabolism, cell cycle regulation and apoptosis, and may contribute to the early phase of MC-LR induced hepatotoxicity. Whereas, this argues that at least some of miRNAs listed in Table 2 are good candidates to pursue in future studies, a key to further elucidation of the miRNA role in the toxicity mechanism is the generation of more complete lists of their numbers and expression changes in healthy and challenged fish.
let-7c | \n\t\t\t6.8 | \n\t\t\tRat sarcoma viral oncogene, RAS | \n\t\t\t[34] | \n\t\t
\n\t\t\t | \n\t\t\t | Myelocytomatosis viral related oncogene, c-MYC | \n\t\t\t[45] | \n\t\t
miR-9b | \n\t\t\t4.4 | \n\t\t\tCaudal related homebox protein, CDX2 | \n\t\t\t[35] | \n\t\t
miR-34a | \n\t\t\t4.0 | \n\t\t\tB-cell lymphoma 2, BCL2 | \n\t\t\t[46] | \n\t\t
\n\t\t\t | \n\t\t\t | Myelocytomatosis viral related oncogene, neuroblastoma derived (avian), MYCN | \n\t\t\t[47] | \n\t\t
miR-16a | \n\t\t\t3.6 | \n\t\t\tB-cell lymphoma 2, BCL2 | \n\t\t\t[36] | \n\t\t
miR-122 | \n\t\t\t2.7 | \n\t\t\tCationic amino acid transporter, CAT-1 | \n\t\t\t[48] | \n\t\t
Reported mammalian silencing targets for differentially expressed miRNAs in MC-LR treated whitefish (100μg/kg body weight) after 24 h of the challenge [33].
*Only miRNAs which were significantly up-regulated (p<0.05) are included in the column.
On the other hand, the lack of p53 stabilization observed in our study infers the presence of alternate checkpoint mechanisms for deregulated growth signals and/or DNA damage in whitefish cells and may suggest post-transcriptional regulation of
We are only beginning to understand the complexities of miRNA-mediated gene regulatory networks in fish cells. It should be expected that environmental contaminants that have the potential to induce oxidative stress and hypoxia in animal cells, like MCs, will also be agents deregulating miRNA expression. In our initial studies [4, 33] we observed rapid changes in liver microRNA levels of whitefish following MC-LR exposure. Bearing in mind a variety of likely silencing targets for and the onset of the aberrant miRNAs expression observed in the study, one may conclude that they are involved in various molecular pathways and may contribute to the early phase of MC-hepatotoxicity. This argues that studied miRNAs are good candidates to pursue in future studies, however, a key to further elucidation of the miRNA role in the toxicity mechanism will be the generation of more complete lists of their numbers and expression changes in healthy and challenged fish, using next generation sequencing methods (Figure 2). As miRNA field continues to evolve, the new markers should help elucidating a variety of issues intrinsic to MC toxicity. As more profiling studies are performed after MC-LR treatment, and on different model organisms, it might be possible to obtain a miRNA snapshot map, the “core of the MC-LR toxicity connectivity grid”. Finally, the revealed miRNA pathways underlying hepatotoxic effects of MC-LR may provide therapeutic targets for a variety of liver diseases.
This work was supported by the Polish Ministry of Science and Higher Education (MNiSW), project UWM No. 0809-0801.
Chronic myeloproliferative disorders are a group of clonal diseases of the stem cell. It is a group of several diseases with some common features. They derive from a multipotential hematopoietic stem cell. A clone of neoplastic cells in all these neoplams is characterized by a lower proliferative activity than that of acute myeloproliferative diseases. In each of these diseases, leukocytosis, thrombocythemia, and polyglobulia may appear at some stage, depending on the diagnosis [1, 2].
The research on interferon has been going on since the 1950s [3]. Then, the attention was paid to its influence on the immune system. It has been noted that it can exert an antiproliferative effect by stimulating cells of the immune system [4]. In 1987, a publication by Ludwig et al. was published, which reported the effectiveness of interferon alpha in the treatment of chronic myeloproliferative disorders [5].
More and more new studies have been showing the effectiveness of interferon alpha in reducing the number of platelets, reducing the need for phlebotomies in patients with polycythemia vera and also in reducing the number of leukocytes. Moreover, interferon reduced the symptoms of myeloproliferative disorders such as redness and itching of the skin. Additionally, it turned out to be effective in reducing the size of the spleen.
Further studies on the assessment of remission using molecular-level response assessments indicate that the interferon action in chronic myeloproliferation diseases targets cells from the mutant clone with no effect on normal bone marrow cells [6].
Over the years, interferon alpha-2a and interferon alpha-2b have been introduced into the treatment of chronic myeloproliferation, followed by their pegylated forms. The introduction of pegylated forms allowed for a reduction in the number of side effects and less frequent administration of the drug to patients. In recent years, monopegylated interferon alpha-2b has been used to further increase the interval between drug administrations while maintaining its antiproliferative efficacy.
The exact mechanism of action of interferon alpha in the treatment of chronic myeloproliferative disease is still not fully understood, but it has an impact on JAK2 (Janus Kinase) signal transducers and activates the STAT signal pathway (Janus Kinase/SignalTransducer and Activator of Transcription).
Interferon alpha binds to IFNAR1 and IFNAR2c, which are type I interferon receptors. Interferon alpha has an impact on JAK2(Janus Kinase) signal transducers and activates the STAT signal pathway. The disturbances in this signaling pathway are observed in chronic myeloproliferative disorders [7].
Interferon inhibits the JAK-STAT signaling pathway by directly inhibiting the action of thrombopoietin in this pathway [8].
So far, three driver mutations have been described in the course of chronic myeloproliferative diseases that affect the functioning of the JAK-STAT pathway.
JAK2 kinase and JAK1, JAK3, and TYK2 kinases belong to the family of non-receptor tyrosine kinases. They are involved in the intracellular signal transduction of the JAK-STAT pathway. It is a system of intracellular proteins used by growth factors and cytokines to express genes that regulate cell activation, proliferation, and differentiation. The mechanism of JAK activation is based on the autophosphorylation of tyrosine residues that occurs after ligand binds to the receptor. JAK2 kinase transmits signals from the hematopoietic cytokine receptors of the myeloid lineage (erythropoietin, granulocyte-colony stimulating factor thrombopoietin, and lymphoid lineage [9].
A somatic G/T point mutation in exon 14 of the JAK2 kinase gene converts valine to phenylalanine at position 617 (V617F) in the JAK2 pseudokinase domain, which allows constitutive, ligand-independent activation of the receptor to trigger a proliferative signal [10].
Mutation of the MPL gene, which encodes the receptor for thrombopoietin, increases the sensitivity of magekaryocytes to the action of thrombopoietin, which stimulates their proliferation [11].
Malfunction of calreticulin as a result of mutation of the CARL gene leads to the activation of the MPL-JAK/STAT signaling pathway, which is independent of the ligand, as calreticulin is responsible, for the proper formation of the MPL receptor. Consequently, there is a clonal proliferation of hematopoietic stem cells [12].
Below, we provide an overview of some clinical studies on the efficacy of interferon in chronic myeloproliferative disorders.
Polycythemia vera (PV) is characterized by an increase in the number of erythrocytes in the peripheral blood.
Polycythemia vera is caused by a clonal mutation in the multipotential hematopoietic stem cell of the bone marrow. The mutation leads to an uncontrolled proliferation of the mutated cell clone, independent of erythropoietin and other regulatory factors. As the mutation takes place at an early stage of hematopoiesis, an increase of the number of erythrocytes as well as of leukocytes and platelets is observed in the peripheral blood. The cause of proliferation in PV independent from external factors is a mutation in the Janus 2 (JAK2) tyrosine kinase gene. The V617F point mutation in the JAK2 gene is responsible for about 96% mutation, and in the remaining cases the mutation arises in exon 12. Both mutations lead to constitutive activation of the JAK-STAT signaling pathway [13].
As a result of the uncontrolled proliferation, blood viscosity increases, which generates symptoms such as headaches and dizziness, visual disturbances, or erythromelalgia. As the number of all hematopoietic cells, including the granulocytes ones, increases, the difficult to control symptoms of their hyperdegranulation may appear, among which gastric ulcer or skin itching is often observed. During the disease progression, the spleen and liver become enlarged.
The most common complication of the disease is episodes of thrombosis, especially arterial one. During the course of the disease, it can also evolve into myelofibrosis or acute myeloid leukemia.
The treatment of PV is aimed at preventing thromboembolic complications, relieving the general symptoms, the appearance of hepatosplenomegaly as well as preventing its progression.
Each patient should receive an antiplatelet drug chronically, and usually acetylsalicylic acid is the choice. Most often, the treatment is started with phlebotomy in order to rapidly lower the hematocrit level. If cytoreductive therapy is necessary, the drugs of first choice are hydroxycarbamide and interferon [2].
However, the research on the mechanism of the action of interferons is still ongoing. In vitro studies with CD34+ cells from peripheral blood of patients diagnosed with polycythemia vera showed that interferon inhibits clonal changed cells selectively. It was found that interferon alpha-2b and pegylated interferon alpha-2a reduce the percentage of cells with JAK2 V617F mutation by about 40%. Pegylated interferon alpha-2a works by activating mitogen-activated protein kinase P38. It affects CD34+ cells of patients with polycythemia vera by increasing the rate of their apoptosis [6].
A case of a patient with PV with a confirmed chromosomal translocation t(6;8) treated with interferon alpha-2b, which resulted in a reduction of the clone with translocation by 50% from the baseline value, was also described [14].
In 2019, the results of a phase II multicenter study were published, which aimed at assessing the effectiveness of recombinant pegylated interferon alpha-2a in cases of refractory to previously hydroxycarbamide therapy. The study included 65 patients with essential thrombocythemia (ET) and 50 patients with polycythemia vera. All patients had previously been treated with hydroxycarbamide and showed resistance to this drug or its intolerance.
The assessment of the response was performed after 12 months of treatment. Overall response rate to interferon was higher in patients diagnosed with ET than in patients with polycythemia vera. In essential thrombocythemia, the percentage of achieved complete remissions was 43 and 26% of partial remissions. The remission rate in ET patients was higher if calreticulin CALR gene mutation was present. Patients with polycythemia vera achieved complete remission in 22% of cases and partial remission in 38% of cases.
Treatment-related side effects that follow to discontinuation of treatment were reported in almost 14% of patients [15].
The duration of response to treatment with pegylated interferon alpha-2a and the assessment of its safety in long-term use in patients with chronic myeloproliferative disorders was the goal of a phase II of the single-center study. Forty-three adult patients with polycythemia vera and 40 patients with essential thrombocythemia were enrolled in the study. The complete hematological response was defined as a decrease in hemoglobin concentration below 15.0 g/l, without phlebotomies, a resolution of splenomegaly, and no thrombotic episodes in the case of PV, and for essential thrombocythemia—a decrease platelet count below 440,000/μl and two other conditions as above. The assessment of the hematological response was performed every 3–6 months. The median follow-up was 83 months.
The hematological response was obtained in 80% of cases for the entire group. In patients with polycythemia vera, 77% of patients achieved a complete response (CR) while 7% a partial response (PR). The duration of response averaged 65 months for CR and 35 months for PR. In the group of patients diagnosed with essential thrombocythemia, CR was achieved in 73% and PR in 3%. The durance of CR was 58 months and PR was 25 months.
The molecular response for the entire group was achieved in 63% of cases.
The overall analysis showed that the duration of hematological remission and its achievement with pegylated interferon alpha-2a treatment is not affected neither by baseline disease characteristics nor JAK2 allele burden and disease molecular status. There was also no effect on age, sex, or the presence of splenomegaly.
During the course of the study, 22% of patients discontinued the treatment, because of toxicity. Toxicity was the greatest at the beginning of treatment. The starting dose was 450 μg per week and was gradually tapered off.
Thus, on the basis of the above observations, the researchers established that pegylated interferon alpha-2a may give long-term hematological and molecular remissions [16].
The assessment of pegylated interferon alpha-2a in group of patients diagnosed with polycythemia vera only was performed. The evaluation was carried out on a group of 27 patients. Interferon decreased the JAK2 V617F allele burden in 89% of cases. In three patients who were JAK2 homozygous at baseline, after the interferon alpha-2a treatment wild-type of JAK2 reappeared. The reduction of the JAK2 allele burden was estimated from 49% to an average 27%, and additional in one patient the mutant JAK2 allele was not detectable after treatment. It can therefore be postulated that the action of pegylated interferon alpha-2a is directed to cells of the polycythemia vera clone [17].
In 2005, the results of treatment by pegylated interferon alpha-2b of 21 patients diagnosed with polycythemia vera and 21 patients diagnosed with essential thrombocythemia were published. In the case of polycythemia vera in 14 patients, PRV-1 gene mutation was initially detected. In 36% of cases, PRV-1 expression normalized after treatment with pegylated interferon alpha-2b. For the entire group of 42 patients, the remission assessment showed that complete remission was achieved in 69% cases after 6 months of treatment. However, only in 19 patients remission was still maintained 2 years after the start of the study. Pegylated interferon alpha-2b was equally effective in patients with PV and ET. The use and the type of prior therapy did not affect the achievement of remission [18].
Another study with enrolled only PV patients included 136 patients. They were divided into two arms. One group received interferon alpha-2b and the other group received hydroxycarbamide. Interferon dosage was administered in 3 million units three times a week for 2 years and then 5 million units two times a week. Hydroxycarbamide was administered at a dose between 15 and 20 mg/kg/day.
In the group of patients treated with interferon, a significantly lower percentage of patients developed erythromelalgia (9.4%) and distal parasthesia (14%) compared with the group treated with hydroxycarbamide, for whom these percentages were respectively: 29 and 37.5%. Interferon alpha-2b was found to be more effective in inducing a molecular response, which was achieved in 54.7% of cases, in comparison with hydroxycarbamide—19.4% of cases, despite the fact that the percentage of achieved general hematological responses did not differ between the groups and amounted about 70%. The 5-year progression free period in the interferon group was achieved in a higher percentage (66%) than in the hydroxycarbamide group (46.7%) [19].
The most recent form of interferon approved by the
Thanks to these changes to the structure of the molecule, it was possible to achieve a significant increase in its half-life. Ropeginterferon can be administered subcutaneously to patients every 14 days. The clinical trials conducted so far have assessed the ropeginterferon dose from 50 micrograms to a maximum dose of 500 microgams administered as standard every 2 weeks. The possible dose change in case of side effects includes not only the reduction of the drug dose itself, but also the extension of the interval between doses. The extension of the dosing interval up to 4 weeks was assessed.
Ropeginterforn was approved in 2019 by the EMA for the use in patients diagnosed with polycythemia vera without splenomegaly, as monotherapy.
Ropeginterferon, like the previous forms of interferons used in treatment, is contraindicated in patients with severe mental disorders, such as severe depression. It is also a contraindication in patients with noncompensatory standard treatment of disorders of the thyroid gland as well as severe forms of autoimmune diseases. The safety profile of ropeginterferon is similar to that of other forms of alpha interferons. The most common side effects are flu-like symptoms [20].
Ropeginterferon has been shown to exhibit in vitro activity against JAK2-mutant cells. The activity of ropeginterferon against JAK2-positive cells is similar to that of other forms of interferons used actually for standard therapy. Ropeginterferon has an inhibitory effect on erythroid progenitor cells with a mutant JAK2 gene. At the same time, it has almost no effect on progenitor cells without the mutated allele (JAK2-wile-type) and normal CD34+ cells. A gradual decrease of JAK2-positive cells was observed in patients with PV during ropeginterferon treatment. The examination was performed after 6 and 12 months of treatment. In comparison, the reduction in the percentage of JAK2 positive cells in patients treated with hydroxycarbamide was significantly lower.
These results may suggest that ropeginterferon may cause elimination of the mutant clone, but further prospective clinical trials are needed to confirm this theory. The evaluation was performed on a group of patients enrolled in the PROUD-PV study who were treated in France [21].
In 2017, a multicenter study was opened in Italy. The study was of the second phase. In total, 127 patients with polycythemia vera were included in the study. All patients enrolled on the study had low-risk PV. The clinical trial consisted of two arms. Patients received phlebotomies and low-dose aspirin in one arm and ropeginterferon in the other arm. The aim of the study was to achieve a hematocrit of 45% or lower without any evidence of disease progression. Ropeginterferon was administered every 2 weeks at a constant dose of 100 μg.
The response to the treatment was assessed after 12 months. The reduction of hematocrit to the assumed level was achieved in significantly higher percentage of patients in the ropeginterferon group than of patients who received only phlebotomies and aspirin. In addition, none of the patients treated with ropeginterferon experienced disease progression during the course of the study, while among those treated with phlebotomies, 8% of patients progressed.
Grade 4 or 5 adverse events were not observed in patients treated with ropeginterferon, and the incidence of remaining adverse event (AE) was small and comparable in both arms. The most common side effects in the ropeginterferon group were flu-like symptoms and neutropenia; however, the third-grade neutropenia was the most common (8% of cases) [22].
One of the most important clinical studies on the use of ropeginterferon was the PROUD-PV study and its continuation: the CONTINUATION-PV study. These were three-phase, multicenter studies. The aim of the study was to compare the effectiveness of ropeginterferon in relation to hydroxycarbamide. The study included adult patients diagnosed with polycythemia vera treated with hydroxycarbamide for less than 3 years and no cytoreductive treatment at all. In total, 257 patients received this treatment. The patients were divided into two groups: those receiving ropeginterferon or the other being given hydroxycarbamide.
During the PROUD-study, drug doses were increased until the hematocrit was achieved below 45% without the use of phlebotomies, and the normalization of the number of leukocytes and platelets was reached.
The PROUD-PV study lasted 12 months. After this time, the patients continued the treatment under the CONTINUATION-PV study for further 36 months. After the final analysis performed in the 12th month at the end of PROUD study, it was found that the hematological response rates did not differ between the ropeginterferon and hydroxycarbamide treatment groups. These were consecutively 43% in the ropeginterferon arm and 46% in the control arm.
However, after analyzing the CONTINUATION- PV study, it turned out that after 36 months of treatment, the rates of hematological responses begin to prevail in the group of patients receiving ropeginterferon, 53% versus 38% in the control group. Thus, from the above data, it can be seen that the response rate to ropeginterferon increases with the duration of treatment [23].
Another analysis of patients participating in the PROUD and CONTINUATION studies was based on the assessment of treatment results after 24 months, dividing patients into two groups according to age (under and over 60 years).
The initial comparison of both groups of patients showed that older patients had a more aggressive course of the disease. Patients over 60 years of age had a higher percentage of cells with a mutant JAK2 allele. They experienced both general symptoms and some complications, such as thrombosis, more frequently. Both patients under 60 years of age and over 60 years of age in the ropeginterferon arm had a higher rate of molecular response, namely 77.1 and 58.7% compared with the HU remission: 33.3 and 36.1%, respectively. Significantly higher reductions in the JAK2 allele were observed in both groups of patients after ropeginterferon treatment: it was 54.8% for younger patients and 35.1% for elderly patients. For comparison, this difference in the group of patients treated with HU was 4.5 and 18.4%, respectively.
What is more, the age did not affect the frequency of ropeginterferon side effects. In addition, the incidence of adverse ropeginterferon disorders was similar to that observed in the hydroxycarbamide group [24].
Essential thrombocythemia is a clonal growth of multipotential stem cells in the bone marrow. The consequence of this is increased proliferation of megakaryocytes in the bone marrow and an increase in the number of platelets in the peripheral blood. The level of platelets above 450,000/μl is considered a diagnostic criterion.
Essential thrombocythemia may progress over time to a more aggressive form of myeloproliferation, i.e., myelofibrosis. The disease can also evolve into acute myeloid leukemia or myelodysplastic syndrome, both with very poor prognosis. Thromboembolic complications are serious, and they concern over 20% of patients. Thrombosis occurs in the artery and venous area. Moreover, in patients with a very high platelet count, above 1,000,000/μl, bleeding may occur as a result of secondary von Willebrand syndrome [1, 2].
The treatment of ET is primarily aimed to prevent thrombotic complications.
In low-risk patients, only acetylsalicylic acid is used. In cases of high-risk patients, hydroxycarbamide is the first-line drug for most patients. Anagrelide and interferon are commonly used as second-line drugs.
Due to the possible effects of hydroxycarbamide of cytogenetic changes in the bone marrow cells after long-lasting usage, some experts recommend the use of interferon in younger patients in the first line. Interferon is also used as the drug of choice in patients planning a pregnancy [25].
The efficacy of pegylated interferon alpha-2a was assessed on the basis of the group of 39 patients with essential thrombocythemia and 40 patients with polycythemia vera.
Of the overall group, 81% of patients were previously treated prior to the study entry. The patients received pegylated interferon alpha-2a in a dose of 90 μg once a week. The dose of 450 μg was associated with a high percentage of intolerance.
In patients with essential thrombocythemia, the complete remission was achieved in 76%, while the overall hematological response rate brought 81%. Moreover, the molecular remission was achieved in 38%, in 14% of cases, JAK2 transcript became not detectable.
Patients diagnosed with polycythemia vera achieved 70% complete hematological remission and 80% general hematological response to treatment. JAK2 transcript was undetectable in 6% of patients. Molecular remission was achieved in 54% of cases.
Pegylated interferon alpha-2a at the dose of 90 μg per week was very well tolerated. In total, 20% of patients experienced a grade of 3 or 4 of adverse reaction, which was neutropenia. In addition, an increase in liver function tests was observed. Grade 4 of AE was not observed among patients who started the treatment with 90 μg/week while grade 3 neutropenia was an adverse event in only 7% of cases [26].
The effect of interferon alpha-2b treatment in patients with ET and PV was investigated. The study was prospective. Some of the results concerning the group of patients with polycythemia vera are presented in the subsection on polycythemia vera. In total, 123 patients with diagnosed essential thrombocythemia participated in the study. All of them received interferon alpha-2b. The patients were divided into two groups depending on the presence of the JAK2 V617F mutation. The enrolled patients were between 18 and 65 years of age. The treatment they received was, sequentially, interferon alpha-2b in the dose of 3 million units three times a week for the first 2 years, after which time the dose was changed into a maintenance dose, which amounted to 5 million units two times a week.
The analysis showed that the patients with the JAK2 V617F mutation present in a higher percentage achieved an overall hematological response as well as a complete hematological response. The overall hematological response was achieved in 83% of patients with JAK2 mutation, and the complete hematological remission was achieved in 23 cases. In the group of ET patients without the JAK2 V617F mutation, overall hematological response was achieved in 61.4%, while the complete hematological remission was achieved in 12 patients. The 5-year progression-free survival was obtained in 75.9% in the JAKV617F group and only in 47.6% without the mutation.
A significant proportion of patients experienced mild side effects. Grade 3 and 4 of adverse events were severe, most of them being a fever. The isolated cases of elevated liver tests and nausea have also been reported [19].
Pegylated interferon alpha-2b in patients with essential thrombocythemia who were previously treated with hydroxycarbamide, anagrelide, and other forms of interferon alpha, however, due to the lack of efficacy or toxicity, the patients required a change of treatment, was assessed. Pegylated interferon alpha-2b turned out to be effective in these cases. It led to the complete hematological remission in 91% of patients after 2 months of therapy, and in 100% of patients after 4 months. However, merely 11 patients participated in the study. Also only two patients required treatment discontinuation due to the side effects such as depression and general fatigue grade 3 [27].
In case of pregnant patients, interferon is currently considered the only safe cytoreductive drug. Over the years, several analyses of the results of interferon treatment during pregnancy have been carried out.
The assessment of 34 pregnancies in 23 women diagnosed with ET was performed retrospectively. All the pregnancies included in the analysis were of high risk. This high risk was associated with a high platelet count above 1,500,000/μl, a history of thrombotic episode, severe microcirculation disorders, or a history of major hemorrhage.
It turned out that the use of interferon allowed the birth of an alive child in 73.5% of cases. There was no difference in efficacy between the basic and pegylated forms of interferon alpha. In pregnancies without interferon treatment, the percentage of live births was only 60%. Moreover, it was not found if the presence of the JAK2 V617F mutation had any influence on the course of pregnancy [28].
An analysis of the course of pregnancy in patients with ET was assessed in Italy. Data from 17 centers were taken into account. Data from 122 pregnancies were collected from 92 women. In patients diagnosed with essential thrombocythemia, the risk of the spontaneous loss of pregnancy is about 2.5 times higher than among the general population. In the contrary to the study quoted above, it was found that the presence of the JAK2 mutation increases the risk of pregnancy loss. The proportion of live births in patients exposed to interferon during pregnancy was 95%, compared with 71.6% in the group of patients not treated with interferon.
The multivariate analysis also showed that the use of acetylsalicylic acid during pregnancy had no effect on the live birth rate of patients with ET [29].
Whatever its form, interferon is the drug of first choice in pregnancy. Hydroxycarbamide and anagrelide should be withdrawn for about 6 months, and at least for 3 months, before the planned conception. Experts recommend the use of interferon in high-risk pregnancies [30]. A Japanese analysis of 10 consecutive pregnancies in ET patients showed 100% live births in patients who received interferon [31].
In myelofibrosis (MF), monoclonal megakaryocytes produce cytokines that stimulate the proliferation of normal, non-neoplastic fibroblasts and stimulate angiogenesis. The consequence of this is the gradual fibrosis of the bone marrow, impaired hematopoiesis in the bone marrow, and the formation of extramedullary location mainly in the sites of fetal hematopoiesis, i.e., in the spleen and the liver.
The production of various cytokines by neoplastic megakaryocytes leads to the proliferation of normal, noncancerous fibroblasts as well as to increased angiogenesis.
Progressive bone marrow fibrosis leads to worsening anemia and thrombocytopenia. On the other hand, the production of proinflammatory cytokines by megakaryoblasts leads to the general symptoms such as weight loss, fever, joint pain, night sweats, and consequently, progressive worsening of general condition.
The prognosis for myelofibrosis is poor. In about 20% of patients, myelofibrosis evolves into acute myeloid leukemia with poor prognosis.
Currently, the only effective method of treatment that gives a chance to prolong the life is allogeneic bone marrow transplantation. However, this method is only available to younger patients.
The goal of treatment of patients who have not been qualified for allotranspalntation is to reduce the symptoms and to improve the patient’s quality of life. In case of leukocytosis cytoreducing drugs, such as hydroxycarbamide, melphalan, or cladribine can be used. They cause a reduction in the number of leukocytes and may, to some extent, inhibit splenomegaly. Interferon alpha has been used successfully for the treatment of myelofibrosis for many years. The results of its effectiveness will be presented below [2].
Currently, the JAK2 inhibitor ruxolitinib is approved for the treatment of myelofibrosis with enlarged spleen in intermediate and high-risk patients. Ruxolitinib reduces the size of the spleen, reduces general symptoms, and improves the quality of life; however, it does not prolong the overall survival of patients [32].
In 2015, the results of a retrospective study were published to compare the histological parameters of the bone marrow before and after interferon treatment. Twelve patients diagnosed with primary myelofibrosis as well as post-PV MF and post-ET MF were enrolled in the study. Patients were treated with pegylated recombinant interferon alpha-2a or recombinant interferon alpha-2b in standard doses. The time of treatment was from 1 to 10 years. Some patients had previously been treated with hydroxycarbamide or anagrelide. In all cases, karyotype was normal. The prognostic factor of Dynamic International Prognostic Scoring System (DIPSS) was assessed at the beginning as well as during the treatment.
Bone marrow cellularity decreased in cases with increased bone marrow cellularity before the treatment. After the interferon treatment, a reduction in the degree of bone marrow fibrosis was found. The parameters, such as the density of naked nuclei and the density of megakaryocytes in the bone marrow, also improved.
It proves that if the JAK2 V617F mutation had been present, DIPSS was decreased after interferon treatment. This relationship was not observed in patients without the JAK2 V617F mutation. The improvement in peripheral blood morphological parameters and the overall clinical improvement correlated with the improvement in the assessed histological parameters of the bone marrow.
Before the initiation of interferon, seven patients had splenomegaly. During the treatment with interferon, the complete resolution of splenomegaly was achieved in 17% of patients (two cases), and its size decreased in 25% (three cases). A good clinical response was achieved in 83% during interferon therapy. There was no significant difference in response between the two types of interferon used [33].
A prospective study was also conducted in patients with low and intermediate-1 risk group myelofibrosis. Seventeen patients were enrolled. Patients received interferon alpha-2b (0.5–3 milion units/three times a week) or pegylated interferon alpha-2a (45–90 μg/week). The duration of therapy was on average 3.3 years.
Most of the patients responded to the treatment. Partial remission was found in seven patients and complete remission in two patients. Moreover, in four cases, the disease was stabilized and in one case the clinical improvement was achieved. Three patients did not respond to treatment at all and progressed to myelofibrosis. Additionally, the assessment in reducing spleen size was performed. At baseline, 15 patients have splenomegaly, nine of them achieved the compete regression of spleen size [34].
However, the efficacy of interferon in the treatment of myelofibrosis appears to be limited only to a less advanced form, when the bone marrow still has an adequate percentage of normal hemopoiesis and the marrow stroma is not significantly fibrotic. In more advanced stages, interferon was not shown to have any significant effect on the regression of the fibrosis process [35].
In 2020, the results of the COMBI study were published. That was a two-phase, multicenter, single-arm study that investigated the efficacy and safety of the combination of ruxolitinib and pegylated interferon alpha. Thirty-two patients with PV and 18 patients with primary and secondary myelofibrosis participated in the study. The patients were at age 18 and older. Remission was achieved in 44% of myelofibrosis cases, including 28% (5 patients) of complete remission. In patients with PV, the results were slightly worse: 31% of remissions, including 9% of complete remissions. Patients received pegylated interferon alpha-2a (45 μg/week) or pegylated interferon alpha-2b (35 μg/week) in low doses and ruxolitinib in doses of 5–20 mg twice a day.
For the entire group of patients (with PV and MF), the initial JAK2 allele burden was 47% at baseline, and after 2 years of treatment with interferon and ruxolitinib, it decreased to 12%.
The treatment toxicity was low. The highest incidence of side effects occurred at initiation of therapy. It was mostly anemia and thrombocytopenia.
The observations from the COMBI study show that, for the combination of interferon in lower doses with ruxolitinib, it may be effective and well tolerated even in the group of patients who had intolerance to interferon used as the only drug in higher doses. The combined treatment improved the bone marrow in terms of fibrosis and its cellularity. It also allowed to improve the value of peripheral blood counts [36].
It is currently known that some of the additional mutations are associated with a worse prognosis in patients with myelorpoliferation, including patients with myelofibrosis. Some of these mutations have been identified as high-risk molecular mutations. These are ASXL1, EZH2, IDH1/2, or SRSF2. Earlier studies have shown their association with a more aggressive course of the disease, worse prognosis, and shorter survival of patients, as well as a poorer response to treatment. Due to their importance, they have been included in the diagnostic criteria of myelofibrosis [37].
It is also known that the presence of driver mutations, i.e., JAK2, CALR, and MPL or triple negativity, may affect the course of myeloproliferation, including the incidence of thromboembolic complications.
The assessment of the influence of driver mutations and a panel of selected additional mutations on the effectiveness of interferon treatment in patients with myelofibrosis was performed on a group of 30 patients. Only the patients with low- and intermediate-1-risk were enrolled in the study. The treatment with pegylated interferon alpha-2a or interferon alpha-2b resulted in a complete remission in two patients and partial remission in nine patients. The disease progressed in three cases. One patient relapsed and four died. The remaining patients achieved a clinical improvement or disease stabilization. In the studied group, it was not found if the effectiveness of interferon treatment was influenced by the lack of driver mutations. Among the group of four patients with additional mutations, two died and one had disease progression. It was a mutation of ASXL1 and SRSF2. The treatment with interferon in patients without additional molecular mutations in the early stages of the disease may prevent further progression of the disease [38].
The side effects of interferon in the group of patients with myelofibrosis are similar to those occurring after the treatment of other chronic myeloproliferative diseases. The most frequently described are hematological toxicity- anemia and thrombocytopenia, less often is the appearance of leukopenia. Hematological toxicity usually resolves with dose reduction or extension of the dose interval. The most frequently nonhematological toxicity was fatigue, muscle pain, weakness, and depression symptoms. All symptoms are usually mild and do not exceed grade 2 [38].
However, the use of interferon in the treatment of myelofibrosis has not been recommended as a standard therapy. Interferon is still being evaluated in clinical trials, or it is used in selected patients as a nonstandard therapy in this diagnosis.
Mastocytosis is characterized by an excessive proliferation of abnormal mast cells and their accumulation in various organs.
The basis for the development of mastocytosis is ligand-independent activation of the KIT receptor, resulting from mutations in the KIT proto-oncogene. The KIT receptor is a trans membrane receptor with tyrosine kinase’s activity. Its activation stimulates the proliferation of mast cells. That excessive numbers of mast cells infiltrate tissues and organs and release mediators such as histamine, interleukine-6, tryptase, heparin, and others, which are responsible for the appearance of symptoms typical of mastocytosis. In addition, the infiltration of tissues for mast cells itself causes damage to the affected organs.
The prognosis of mastocytosis depends on the type of the disease. In the case of cutaneous mastocytosis (CM), in the majority of cases prognosis is good and the disease does not shorten the patient’s life, but in aggressive systemic mastocytosis (ASM), the average follow-up is about 40 months. Mast cell leukemia has a poor prognosis with a median follow-up of approximately 1 year.
Systemic mastocytosis usually requires the implementation of cytoreductive therapy. The first line of therapy is interferon alone or its combination with corticosteroids. In aggressive systemic mastocytosis, the first line in addition to interferon 2-CdA can be used. An effective drug turned out to be midostaurin in the case of the present KIT mutation. In patients without the KIT D816V mutation, treatment with imatinib may be effective. In the case of mast cell leukemia, multidrug chemotherapy is most often required, as in acute leukemias, followed by bone marrow transplantation [39].
Systemic mastocytosis requiring treatment is a rare disease, this is why the studies available in the literature evaluating various therapies concern mostly small groups of patients.
In 2002, the French authors presented their experiences on the use of interferon in patients with systemic mastocytosis. They included 20 patients. The patients received interferon alpha-2b in gradually increased doses.
The patients were assessed after 6 months. In cases in which bone marrow was infiltrated for mast cells at baseline, it still remained infiltrated after 6 months of treatment.
However, the responses were obtained in terms of symptoms related to mast cell degranulation. Partial remission was achieved in 35% of patients and minor remission in 30%. It concerns mainly skin lesions and vascular congestion. Moreover, the assessment of the histamine level in the plasma revealed a decrease of it in patients who previously presented symptoms related to the degranulation of mast cells, such as gastrointestinal disorders and flushing.
A high percentage of side effects were found during treatment. They concerned 35% of patients. Depression and cytopenia were most frequent ones [40].
Another analysis was a report of five patients with systemic mastocytosis treated with interferon and prednisolone. All patients received interferon alpha-2b in a dose of 3 million units three times a week and four patients additionally received prednisolone. Four patients responded to interferon treatment at varying degrees. One patient, who at baseline had bone marrow involvement by mast cells in above 10%, progressed to mast cell leukemia. In two patients, the symptoms C resolved completely and in one of them they partially disappeared. In one case, stabilizing disease was achieved [41].
In 2009, a retrospective analysis of patients treated with cytoreductive therapy due to mastocytosis was published. The authors collected data from 108 patients treated at the Mayo Clinic. This analysis allowed for the comparison of the efficacy of four drugs used in systemic mastocytosis. There were interferon alpha alone or in the combination with prednisone—among 40 patients, hydroxycarbamide—among 26 ones, imatinib—among 22 persons, and 2-chlorodeoxyadenosine (2-CdA)—among 22 patients.
After dividing the patients into three additional groups on the basis of the type of mastocytosis—indolent systemic mastocytosis, aggressive systemic mastocytosis, and systemic mastocytosis associated with another clonal hematological nonmast cell lineage disease (SM-AHNMD)—the effectiveness of each of type of therapy was assessed.
The highest response rates in indolent and aggressive mastocytosis were achieved with interferon treatment. They were 60% of the responses in both groups, and in the SM-AHNMD group of patients, the percentage was also one of the highest and amounted to 45%. The second most effective drug was 2-CdA. The response rates were 56% for indolent MS, 50% for aggressive MS, and 55% for SM-AHNMD. The patients treated with imatinib achieved response in 14, 50, and 9% by following groups, respectively. In contrast, patients with indolent and aggressive systemic mastocytosis did not respond to hydroxycarbamide treatment at all. The response rate in both groups was 0%. However, patients with MS associated with another clonal hematological nonmast cell lineage disease achieved 21% response to hydroxycarbamide. Additionally, it was found that only interferon relieved symptoms caused by the release of inflammatory mediators by mast cells.
The additional analysis showed no influence of the TET 2 mutation on the response to treatment [42].
In the literature, there are also single cases of mastocytosis presenting trials of nonstandard treatment. That is description of a patient with systemic mastocytosis with mast cell bone marrow involvement. Mutation of c-kit Asp816Val was present. Patient progressed despite treatment with dasatinib and 2-chlorodeoxyadenosine. The patient developed symptoms related to the degranulation of mast cells and increased ascites.
The patient was treated with pranlukast, which is an anti-leukotriene receptor antagonist due to an asthma episode. The rate of ascites growth decreased significantly after one administration. The patient required paracentesis every 10 days and not every 3 days, as before starting to take the drug. After 15 days of treatment with pranlukast, the patient received interferon alpha, which resulted in complete regression of ascites, resolution of pancytopenia, and complete disappearance of the c-kit mutation clone. The infiltration of mast cells in the bone marrow significantly decreased [43].
Interferon alpha was also effective in a patient with systemic mastocytosis associated with myelodysplastic syndrome with the c-kit D816V mutation, which was refractory to imatinib treatment [44].
Interferon alpha also proved to be effective in the treatment of osteoporotic lesions appearing in the course of mastocytosis.
The series of 10 cases with resolved mastocytosis and osteoporosis-related fractures was presented in 2011. The patients received interferon alpha in a dose of 1.5 million units three times a week as well as pamindronic acid. The patients were treated for an average of 60 months. For the first 2 years, pamindronate was given at a dose of 1 mg/kg every month, and then every 3 months.
During the course of the study, no patient had a new-bone fracture. The level of alkaline phosphatase decreased by 25% in relation to the value before treatment and tryptase by 34%. Bone density increased during treated with interferon and pamindronate. The increase was on average 12% in the spine bones and 1.9% in the hip bones. At the same time, there was no increase in the density of the hip bone and a minimal increase in the density of the spine in patients treated with pamindronate alone.
The results of this observation suggest that it is beneficial to add low doses of interferon alpha to pamindronate treatment in terms of bone density increase [45].
That experiences show that interferon used in systemic mastocytosis significantly improves the quality of life of patients by inhibiting the symptoms caused by degranulation of mast cells. They prevent bone fractures and, in some patients, they cause remission of bone marrow infiltration by mast cells.
Chronic neutrophilic leukemia (CNL) is a very rare disease. It is characterized by the clonal proliferation of mature neutrophils.
The diagnostic criteria proposed by the World Health Organization (WHO) comprise leukocyte counts above 25,000/μl (including more than 80% of rod and segmented
Physical examination often shows enlargement of the liver and spleen, moreover, patients complain on weight loss and weakness [1].
The prognosis varies. The average survival time for patients with CNL is less than 2 years.
Only few descriptions of chronic neutrophilic leukemia are available in the literature, and these are mostly single case reports.
Because it is an extremely rare disease, there are no established and generally accepted treatment standards. In most cases, patients are given hydroxycarbamide or interferon. Patients who are eligible for a bone marrow transplant may benefit from this treatment. Bone marrow allotransplantation remains the only method that gives a chance for a significant extension of life.
The German authors presented a series of 14 cases of chronic neutrophilic leukemia. The group of patients consisted of eight women and six men. The average age was 64.7 years. From the entire group of patients, longer survival was achieved only in three cases. One of these patients was treated with interferon alpha and achieved hematological remission, the other underwent bone marrow allotransplantation from a family donor, and the third one was treated with hydroxycarbamide and transfusions as needed. The follow-up period of the patient after allogeneic matched related donor transplantation (allo-MRD) was 73 months, and for the patient after interferon treatment it was 41 months.
The remaining patients died within 2 years of diagnosis. Six patients, the largest group, died due to intracranial bleeding, three patients died because of leukemia cell tissue infiltration, one patient because of the disease transformation into leukemia, and one patient because of pneumonia [46].
It can be seen from these experiences that treatment with interferon alpha can significantly extend the survival time of patients.
The case of a 40-year-old woman diagnosed with chronic neutrophilic leukemia is presented by Yassin and coauthors. Initially, the patient had almost 41,000 leukocytes in the peripheral blood. In a physical examination, splenomegaly and hepatomegaly were not present. Patient received pegylated interferon alpha-2a. The initially dose was 50 μg once a week for the first 2 weeks, then the dose was increased to 135 μg weekly for 6 weeks, and then the dose interval was extended to another 2 weeks. As a result of the treatment, the general condition of the patient improved and the parameters of peripheral blood counts were normalized [47].
Another case report presented in the literature describes a 41-year-old woman diagnosed with CNL accompanied by focal segmental glomerulosclerosis (FSGS). The patient had increasing leukocytosis for several months. On the admission to the hospital, leukocytosis was 94,000/μl. Moreover, the number of platelets in the morphology exceeded 1,000,000/μl. More than a year earlier, the patient had splenectomy due to splenomegaly and spleen infraction.
Additionally, JAK2 V617F mutation was found. Some authors suggest that the presence of JAK2 mutation may be associated with longer survival in CNL.
The patient received hydroxycarbamide for 3 months and reduction in the number of leukocytes was achieved. After this time, interferon alpha-2b was added to hydroxycarbamide. As a result, focal segmental glomerulosclerosis disappeared and the renal tests improved [48].
Another case of chronic neutrophilic leukemia with a JAK2 gene mutation concerns a 53-year-old man. The patient’s baseline leukocytosis was 33,500/μl, including the neutrophil count of 29,700/μl. The patient also had splenomegaly.
The treatment with interferon alpha-2b at a dose of 3 million units every other day was started. After a month of treatment, the number of leukocytes was reduced to less than 10,000/μl. Then the patient was treated chronically with interferon alpha-2b in doses of 3 million units every 2 weeks. As a result of the therapy, the number of leukocytes remains between 8 and 10,000/μl. The patient remains in general good condition [49].
A series of two CNL cases are also shown. The first patient was a 70-year-old woman with stable leukocytosis of about 35,000/μl and the remaining morphology parameters in normal range. The patient was only observed for 5 years until hepasplenomegaly progressed rapidly. Then, interferon alpha-2b was included. Due to the treatment, the rapid regression of hepatosplenomegaly was achieved.
The second case is a 68-year-old woman with baseline leukocytosis of almost 14,000/μl. In this case, the treatment with hydroxycarbamide was started immediately. However, no improvement was achieved. After 6 weeks of HU treatment, interferon alpha-2b 3 million units 3 times a week was implemented and leukocytosis decreased. Due to the interferon treatment, the disease stabilized for a long time. Because the patient experienced an adverse reaction, a severe flu-like syndrome, interferon was discontinued. After interferon withdrawal, the disease progressed gradually and the treatment attempts by busulfan and 6-mercaptopurine were unsuccessful. Therefore, interferon was readministered and the disease went into remission. Interferon treatment was continued at a reduced dose. The disease regression was achieved again.
Additionally, the patient showed an improvement in the function of granulocytes in terms of phagocytosis and an improvement in neutral killer (NK) cell function after treatment with interferon [50].
The above examples show that interferon alpha is effective in the treatment of chronic neutrophilic leukemia. The side effects are rare and can be managed with dose reductions. Moreover, in these cases, interferon is also effective in a reduced dose. Disease remission or regression can be achieved without typical of CNL complications, such as intracranial bleeding.
Interferon has been used in the past to treat chronic myeloid leukemia. The treatment with tyrosine kinase inhibitors is now a standard practice. However, in a small number of patients, they are ineffective or exhibit unmanageable toxicity. Therefore, the attempts are underway to use interferon in combination with TKI in lower doses, which is to ensure the enhancement of the antiproliferative effect while reducing the toxicity.
There are ongoing attempts to use ropeginterferon in patients diagnosed with chronic myeloid leukemia, in whom treatment with imatinib alone has not led to deep molecular response (DMR). The first phase study was conducted in a small group of patients with chronic myeloid leukemia. The patients in first chronic phase treated with imatinib who did not achieve DMR, but in complete hematologic remission and complete cytogenetic remission, were included in the study. Patients have been treated with imatinib for at least 18 months. Twelve patients were enrolled in the study, and they completed the study according to the protocol. These patients received additional ropeginterferon to imatinib and four achieved DMR. Low toxicity was observed during the treatment. Among the hematological toxicities, neutropenia was the most common. There was no nonhematological toxicity with a degree higher than 1/2 during the treatment. Moreover, it has been found that better effects and fewer side effects are obtained when ropeginterferon is administered for a longer time, but in lower doses. The comparison of the effectiveness of interferon in chronic myeloproliferative disorders based on selected articles is presented in Table 1 [51].
Source | Type of trial | Interferon | Diagnosis | No. | Prior treatment status | Response rate |
---|---|---|---|---|---|---|
Yacoubet al. [15] | Phase II, multicenter | Pegylated IFN alfa-2a | PV | 50 | Resistance to HU or HU intolerance | CR:22% PR:38% |
ET | 65 | CR:43% PR:26% | ||||
Masarova et al. [16] | Phase II, single-center | Pegylated IFN alfa-2a | PV | 43 | Untreated or previously treated with cytoreductive therapy | CR:77% PR:7% |
ET | 40 | CR:73% PR:3% | ||||
Samuelsson et al. [18] | Phase II | Pegylated IFN alfa-2b | PV | 21 | Untreated or previously treated with cytoreductive therapy | CR: 69% for the entire group |
ET | 21 | |||||
Huang BT et al. [19] | Open label, multicenter | IFN alfa-2b | PV | 136 | Untreated or previously treated with cytoreductive therapy | OHR:70% Molecular response:54.7% |
ET | 123 | OHR (JAK2+ patients):83% CHR:23 cases OHR (JAK2-patients): 61.4% CHR:12 cases | ||||
Gisslinger et al. [23] | phase III, multicenter | Ropeginterferon | PV | 257 | Previously treated | OHR:53% |
Quintás-Cardama et al. [26] | phase II | Pegylated IFN alfa-2a | PV | 40 | Untreated or previously treated with cytoreductive therapy | OHR:80% CR:70% Molecular remission:54% |
ET | 39 | OHR:81% CR:76% Molecular remission:38% | ||||
Sørensen et al. [36] | Phase III, multicenter, COMBI | Pegylated IFN alfa-2a with ruxolitinib or Pegylated IFN alfa-2b with ruxolitinib | PV | 32 | Untreated or previously treated with cytoreductive therapy | OHR:44% CR:28% |
MF | 18 | OHR:31% CR:9% | ||||
Casassus et al. [40] | Open label, multicenter | IFN alpha-2b | Mastocytosis | 20 | Untreated and previously treated | PR:35% Minor remission: 30% |
Comparison of the effectiveness of interferon in chronic myeloproliferative disorders.
PV: polycythemia vera; ET: essential thrombocythemia; MF: myelofibrosis; HU: hydroxycarbamide/hydroxyurea; CR: complete remission; PR: partial remission; and OHR: overall hematological response.
Interferon alpha appears to be an effective and safe drug in the most type of chronic myeloproliferative disorders. Nowadays, all forms of its using have similar effectiveness. Interferon alpha can be effective even in cases of resistance for first-line treatment. Trial research is currently underway to combine it with some new drugs, such as ruxolitinib, and to add it to the already well-established therapy, it is a promising option for patients with refractory disease.
From time to time, new forms of interferon, such as ropeginterferon, are introduced, which gives hope for better effectiveness, better safety profile, and greater comfort in its use for patients who have to be treated for many years. In the case of the use of interferons alpha in the treatment of chronic myeloproliferative diseases, there are still opportunities to extend its use and to study its combination with newly introduced drugs.
IntechOpen implements a robust policy to minimize and deal with instances of fraud or misconduct. As part of our general commitment to transparency and openness, and in order to maintain high scientific standards, we have a well-defined editorial policy regarding Retractions and Corrections.
",metaTitle:"Retraction and Correction Policy",metaDescription:"Retraction and Correction Policy",metaKeywords:null,canonicalURL:"/page/retraction-and-correction-policy",contentRaw:'[{"type":"htmlEditorComponent","content":"IntechOpen’s Retraction and Correction Policy has been developed in accordance with the Committee on Publication Ethics (COPE) publication guidelines relating to scientific misconduct and research ethics:
\\n\\n1. RETRACTIONS
\\n\\nA Retraction of a Chapter will be issued by the Academic Editor, either following an Author’s request to do so or when there is a 3rd party report of scientific misconduct. Upon receipt of a report by a 3rd party, the Academic Editor will investigate any allegations of scientific misconduct, working in cooperation with the Author(s) and their institution(s).
\\n\\nA formal Retraction will be issued when there is clear and conclusive evidence of any of the following:
\\n\\nPublishing of a Retraction Notice will adhere to the following guidelines:
\\n\\n1.2. REMOVALS AND CANCELLATIONS
\\n\\n2. STATEMENTS OF CONCERN
\\n\\nA Statement of Concern detailing alleged misconduct will be issued by the Academic Editor or publisher following a 3rd party report of scientific misconduct when:
\\n\\nIntechOpen believes that the number of occasions on which a Statement of Concern is issued will be very few in number. In all cases when such a decision has been taken by the Academic Editor the decision will be reviewed by another editor to whom the author can make representations.
\\n\\n3. CORRECTIONS
\\n\\nA Correction will be issued by the Academic Editor when:
\\n\\n3.1. ERRATUM
\\n\\nAn Erratum will be issued by the Academic Editor when it is determined that a mistake in a Chapter originates from the production process handled by the publisher.
\\n\\nA published Erratum will adhere to the Retraction Notice publishing guidelines outlined above.
\\n\\n3.2. CORRIGENDUM
\\n\\nA Corrigendum will be issued by the Academic Editor when it is determined that a mistake in a Chapter is a result of an Author’s miscalculation or oversight. A published Corrigendum will adhere to the Retraction Notice publishing guidelines outlined above.
\\n\\n4. FINAL REMARKS
\\n\\nIntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\\n\\nIn the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\\n\\nThe general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
\\n\\nAny suggestions or comments on this Policy are welcome and may be sent to permissions@intechopen.com.
\\n\\nPolicy last updated: 2017-09-11
\\n"}]'},components:[{type:"htmlEditorComponent",content:'IntechOpen’s Retraction and Correction Policy has been developed in accordance with the Committee on Publication Ethics (COPE) publication guidelines relating to scientific misconduct and research ethics:
\n\n1. RETRACTIONS
\n\nA Retraction of a Chapter will be issued by the Academic Editor, either following an Author’s request to do so or when there is a 3rd party report of scientific misconduct. Upon receipt of a report by a 3rd party, the Academic Editor will investigate any allegations of scientific misconduct, working in cooperation with the Author(s) and their institution(s).
\n\nA formal Retraction will be issued when there is clear and conclusive evidence of any of the following:
\n\nPublishing of a Retraction Notice will adhere to the following guidelines:
\n\n1.2. REMOVALS AND CANCELLATIONS
\n\n2. STATEMENTS OF CONCERN
\n\nA Statement of Concern detailing alleged misconduct will be issued by the Academic Editor or publisher following a 3rd party report of scientific misconduct when:
\n\nIntechOpen believes that the number of occasions on which a Statement of Concern is issued will be very few in number. In all cases when such a decision has been taken by the Academic Editor the decision will be reviewed by another editor to whom the author can make representations.
\n\n3. CORRECTIONS
\n\nA Correction will be issued by the Academic Editor when:
\n\n3.1. ERRATUM
\n\nAn Erratum will be issued by the Academic Editor when it is determined that a mistake in a Chapter originates from the production process handled by the publisher.
\n\nA published Erratum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n3.2. CORRIGENDUM
\n\nA Corrigendum will be issued by the Academic Editor when it is determined that a mistake in a Chapter is a result of an Author’s miscalculation or oversight. A published Corrigendum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n4. FINAL REMARKS
\n\nIntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\n\nIn the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\n\nThe general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
\n\nAny suggestions or comments on this Policy are welcome and may be sent to permissions@intechopen.com.
\n\nPolicy last updated: 2017-09-11
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{},profiles:[{id:"396",title:"Dr.",name:"Vedran",middleName:null,surname:"Kordic",slug:"vedran-kordic",fullName:"Vedran Kordic",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/396/images/7281_n.png",biography:"After obtaining his Master's degree in Mechanical Engineering he continued his education at the Vienna University of Technology where he obtained his PhD degree in 2004. He worked as a researcher at the Automation and Control Institute, Faculty of Electrical Engineering, Vienna University of Technology until 2008. His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. He has contributed in stochastic estimation of control area especially, in the Multiple Target Tracking and Interactive Multiple Model (IMM) research, Ball & Beam Control Problem, Robotics, Levitation Control. He has contributed in developing Algorithms for Fingerprint Matching, Computer Vision and Face Recognition. He has been supervising Pattern Recognition, Formal Languages and Distributed Processing projects for several years. He has reviewed many books on Management, Computer Science. Currently, he is an active and permanent reviewer for many international conferences and symposia and the program committee member for many international conferences.\nIn teaching he has taught the core computer science subjects like, Digital Design, Real Time Embedded System Programming, Operating Systems, Software Engineering, Data Structures, Databases, Compiler Construction. In the Engineering side, Digital Signal Processing, Computer Architecture, Electronics Devices, Digital Filtering and Engineering Management.\nApart from his Academic Interest and activities he loves sport especially, Cricket, Football, Snooker and Squash. He plays cricket for Esbjerg city in the second division team as an opener wicket keeper batsman. He is a very good player of squash but has not played squash since his arrival in Denmark.",institutionString:null,institution:null},{id:"611",title:"Prof.",name:"T",middleName:null,surname:"Nagarajan",slug:"t-nagarajan",fullName:"T Nagarajan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universiti Teknologi Petronas",country:{name:"Malaysia"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:13389},{group:"region",caption:"Middle and South America",value:2,count:11661},{group:"region",caption:"Africa",value:3,count:4168},{group:"region",caption:"Asia",value:4,count:22334},{group:"region",caption:"Australia and Oceania",value:5,count:2019},{group:"region",caption:"Europe",value:6,count:33642}],offset:12,limit:12,total:135275},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{hasNoEditors:"1",sort:"dateEndThirdStepPublish"},books:[{type:"book",id:"11616",title:"Foraging",subtitle:null,isOpenForSubmission:!0,hash:"955b60bb658c8d1a09dd4efc9bf6674b",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11616.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11632",title:"Updated Research on Bacteriophages",subtitle:null,isOpenForSubmission:!0,hash:"d34dfa0d5d10511184f97ddaeef9936b",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11632.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11730",title:"Midwifery",subtitle:null,isOpenForSubmission:!0,hash:"95389fcd878d0e929234c441744ba398",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11730.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11697",title:"Scoliosis",subtitle:null,isOpenForSubmission:!0,hash:"fa052443744b8f6ba5a87091e373bafe",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11697.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11699",title:"Neonatal Surgery",subtitle:null,isOpenForSubmission:!0,hash:"e52adaee8e54f51c2ba4972daeb410f7",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11699.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11773",title:"Archaeology - Challenges and Updates",subtitle:null,isOpenForSubmission:!0,hash:"17d91462fa926279f65164ac0d5641cd",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11773.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11776",title:"Fashion Industry",subtitle:null,isOpenForSubmission:!0,hash:"e8d53d1029a7bccf825aa55d43fecc68",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11776.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11794",title:"Coconut Cultivation",subtitle:null,isOpenForSubmission:!0,hash:"48e1cb42a4162f64cae3a2e777472f21",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11794.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11797",title:"Clostridium difficile",subtitle:null,isOpenForSubmission:!0,hash:"4cb066b44bb8d4a8b93a627de26e3ebf",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11797.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11809",title:"Lagomorpha",subtitle:null,isOpenForSubmission:!0,hash:"1e8fd5779205c16e5797b05455dc5be0",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11809.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11818",title:"Uveitis",subtitle:null,isOpenForSubmission:!0,hash:"f8c178e6f45ba7b500281005b5d5b67a",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11818.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11837",title:"Ecology and Geography of the Mediterranean",subtitle:null,isOpenForSubmission:!0,hash:"bbb25987a982d61da4f47fb13614ba3c",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11837.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:29},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:3},{group:"topic",caption:"Business, Management and Economics",value:7,count:3},{group:"topic",caption:"Chemistry",value:8,count:12},{group:"topic",caption:"Computer and Information Science",value:9,count:7},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:11},{group:"topic",caption:"Engineering",value:11,count:18},{group:"topic",caption:"Environmental Sciences",value:12,count:4},{group:"topic",caption:"Immunology and Microbiology",value:13,count:8},{group:"topic",caption:"Materials Science",value:14,count:7},{group:"topic",caption:"Mathematics",value:15,count:5},{group:"topic",caption:"Medicine",value:16,count:79},{group:"topic",caption:"Neuroscience",value:18,count:6},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:6},{group:"topic",caption:"Physics",value:20,count:1},{group:"topic",caption:"Psychology",value:21,count:6},{group:"topic",caption:"Robotics",value:22,count:2},{group:"topic",caption:"Social Sciences",value:23,count:22}],offset:12,limit:12,total:229},popularBooks:{featuredBooks:[{type:"book",id:"7827",title:"Interpersonal Relationships",subtitle:null,isOpenForSubmission:!1,hash:"ebf41f4d17c75010eb3294cc8cac3d47",slug:"interpersonal-relationships",bookSignature:"Martha Peaslee Levine",coverURL:"https://cdn.intechopen.com/books/images_new/7827.jpg",editors:[{id:"186919",title:"Dr.",name:"Martha",middleName:null,surname:"Peaslee Levine",slug:"martha-peaslee-levine",fullName:"Martha Peaslee Levine"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10808",title:"Current Concepts in Dental Implantology",subtitle:"From Science to Clinical Research",isOpenForSubmission:!1,hash:"4af8830e463f89c57515c2da2b9777b0",slug:"current-concepts-in-dental-implantology-from-science-to-clinical-research",bookSignature:"Dragana Gabrić and Marko Vuletić",coverURL:"https://cdn.intechopen.com/books/images_new/10808.jpg",editors:[{id:"26946",title:"Prof.",name:"Dragana",middleName:null,surname:"Gabrić",slug:"dragana-gabric",fullName:"Dragana Gabrić"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10796",title:"Extracellular Vesicles",subtitle:"Role in Diseases, Pathogenesis and Therapy",isOpenForSubmission:!1,hash:"eb5407fcf93baff7bca3fae5640153a2",slug:"extracellular-vesicles-role-in-diseases-pathogenesis-and-therapy",bookSignature:"Manash K. Paul",coverURL:"https://cdn.intechopen.com/books/images_new/10796.jpg",editors:[{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10908",title:"Advances in Decision Making",subtitle:null,isOpenForSubmission:!1,hash:"126486f7f91e18e2e3539a32c38be7b1",slug:"advances-in-decision-making",bookSignature:"Fausto Pedro García Márquez",coverURL:"https://cdn.intechopen.com/books/images_new/10908.jpg",editors:[{id:"22844",title:"Prof.",name:"Fausto Pedro",middleName:null,surname:"García Márquez",slug:"fausto-pedro-garcia-marquez",fullName:"Fausto Pedro García Márquez"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"95",title:"Applications and Experiences of Quality Control",subtitle:null,isOpenForSubmission:!1,hash:"4bcb22b1eee68210a977a97d5a0f363a",slug:"applications-and-experiences-of-quality-control",bookSignature:"Ognyan Ivanov",coverURL:"https://cdn.intechopen.com/books/images_new/95.jpg",editors:[{id:"22230",title:"Prof.",name:"Ognyan",middleName:null,surname:"Ivanov",slug:"ognyan-ivanov",fullName:"Ognyan Ivanov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"2160",title:"MATLAB",subtitle:"A Fundamental Tool for Scientific Computing and Engineering Applications - Volume 1",isOpenForSubmission:!1,hash:"dd9c658341fbd264ed4f8d9e6aa8ca29",slug:"matlab-a-fundamental-tool-for-scientific-computing-and-engineering-applications-volume-1",bookSignature:"Vasilios N. Katsikis",coverURL:"https://cdn.intechopen.com/books/images_new/2160.jpg",editors:[{id:"12289",title:"Prof.",name:"Vasilios",middleName:"N.",surname:"Katsikis",slug:"vasilios-katsikis",fullName:"Vasilios Katsikis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"3560",title:"Advances in Landscape Architecture",subtitle:null,isOpenForSubmission:!1,hash:"a20614517ec5f7e91188fe8e42832138",slug:"advances-in-landscape-architecture",bookSignature:"Murat Özyavuz",coverURL:"https://cdn.intechopen.com/books/images_new/3560.jpg",editors:[{id:"93073",title:"Dr.",name:"Murat",middleName:null,surname:"Ozyavuz",slug:"murat-ozyavuz",fullName:"Murat Ozyavuz"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10739",title:"Global Decline of Insects",subtitle:null,isOpenForSubmission:!1,hash:"543783652b9092962a8fa4bed38eeb17",slug:"global-decline-of-insects",bookSignature:"Hamadttu Abdel Farag El-Shafie",coverURL:"https://cdn.intechopen.com/books/images_new/10739.jpg",editors:[{id:"192142",title:"Dr.",name:"Hamadttu",middleName:null,surname:"Abdel Farag El-Shafie",slug:"hamadttu-abdel-farag-el-shafie",fullName:"Hamadttu Abdel Farag El-Shafie"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10911",title:"Higher Education",subtitle:"New Approaches to Accreditation, Digitalization, and Globalization in the Age of Covid",isOpenForSubmission:!1,hash:"223a02337498e535e967174c1f648fbc",slug:"higher-education-new-approaches-to-accreditation-digitalization-and-globalization-in-the-age-of-covid",bookSignature:"Lee Waller and Sharon Waller",coverURL:"https://cdn.intechopen.com/books/images_new/10911.jpg",editors:[{id:"263301",title:"Dr.",name:"Lee",middleName:null,surname:"Waller",slug:"lee-waller",fullName:"Lee Waller"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"3568",title:"Recent Advances in Plant in vitro Culture",subtitle:null,isOpenForSubmission:!1,hash:"830bbb601742c85a3fb0eeafe1454c43",slug:"recent-advances-in-plant-in-vitro-culture",bookSignature:"Annarita Leva and Laura M. R. Rinaldi",coverURL:"https://cdn.intechopen.com/books/images_new/3568.jpg",editors:[{id:"142145",title:"Dr.",name:"Annarita",middleName:null,surname:"Leva",slug:"annarita-leva",fullName:"Annarita Leva"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"3737",title:"MATLAB",subtitle:"Modelling, Programming and Simulations",isOpenForSubmission:!1,hash:null,slug:"matlab-modelling-programming-and-simulations",bookSignature:"Emilson Pereira Leite",coverURL:"https://cdn.intechopen.com/books/images_new/3737.jpg",editors:[{id:"12051",title:"Prof.",name:"Emilson",middleName:null,surname:"Pereira Leite",slug:"emilson-pereira-leite",fullName:"Emilson Pereira Leite"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"1770",title:"Gel Electrophoresis",subtitle:"Principles and Basics",isOpenForSubmission:!1,hash:"279701f6c802cf02deef45103e0611ff",slug:"gel-electrophoresis-principles-and-basics",bookSignature:"Sameh Magdeldin",coverURL:"https://cdn.intechopen.com/books/images_new/1770.jpg",editors:[{id:"123648",title:"Dr.",name:"Sameh",middleName:null,surname:"Magdeldin",slug:"sameh-magdeldin",fullName:"Sameh Magdeldin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:4797},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"7827",title:"Interpersonal Relationships",subtitle:null,isOpenForSubmission:!1,hash:"ebf41f4d17c75010eb3294cc8cac3d47",slug:"interpersonal-relationships",bookSignature:"Martha Peaslee Levine",coverURL:"https://cdn.intechopen.com/books/images_new/7827.jpg",publishedDate:"July 27th 2022",numberOfDownloads:7175,editors:[{id:"186919",title:"Dr.",name:"Martha",middleName:null,surname:"Peaslee Levine",slug:"martha-peaslee-levine",fullName:"Martha Peaslee Levine"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10808",title:"Current Concepts in Dental Implantology",subtitle:"From Science to Clinical Research",isOpenForSubmission:!1,hash:"4af8830e463f89c57515c2da2b9777b0",slug:"current-concepts-in-dental-implantology-from-science-to-clinical-research",bookSignature:"Dragana Gabrić and Marko Vuletić",coverURL:"https://cdn.intechopen.com/books/images_new/10808.jpg",publishedDate:"July 27th 2022",numberOfDownloads:1981,editors:[{id:"26946",title:"Prof.",name:"Dragana",middleName:null,surname:"Gabrić",slug:"dragana-gabric",fullName:"Dragana Gabrić"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10796",title:"Extracellular Vesicles",subtitle:"Role in Diseases, Pathogenesis and Therapy",isOpenForSubmission:!1,hash:"eb5407fcf93baff7bca3fae5640153a2",slug:"extracellular-vesicles-role-in-diseases-pathogenesis-and-therapy",bookSignature:"Manash K. Paul",coverURL:"https://cdn.intechopen.com/books/images_new/10796.jpg",publishedDate:"July 20th 2022",numberOfDownloads:2308,editors:[{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10908",title:"Advances in Decision Making",subtitle:null,isOpenForSubmission:!1,hash:"126486f7f91e18e2e3539a32c38be7b1",slug:"advances-in-decision-making",bookSignature:"Fausto Pedro García Márquez",coverURL:"https://cdn.intechopen.com/books/images_new/10908.jpg",publishedDate:"July 27th 2022",numberOfDownloads:1473,editors:[{id:"22844",title:"Prof.",name:"Fausto Pedro",middleName:null,surname:"García Márquez",slug:"fausto-pedro-garcia-marquez",fullName:"Fausto Pedro García Márquez"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"95",title:"Applications and Experiences of Quality Control",subtitle:null,isOpenForSubmission:!1,hash:"4bcb22b1eee68210a977a97d5a0f363a",slug:"applications-and-experiences-of-quality-control",bookSignature:"Ognyan Ivanov",coverURL:"https://cdn.intechopen.com/books/images_new/95.jpg",publishedDate:"April 26th 2011",numberOfDownloads:318571,editors:[{id:"22230",title:"Prof.",name:"Ognyan",middleName:null,surname:"Ivanov",slug:"ognyan-ivanov",fullName:"Ognyan Ivanov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"2160",title:"MATLAB",subtitle:"A Fundamental Tool for Scientific Computing and Engineering Applications - Volume 1",isOpenForSubmission:!1,hash:"dd9c658341fbd264ed4f8d9e6aa8ca29",slug:"matlab-a-fundamental-tool-for-scientific-computing-and-engineering-applications-volume-1",bookSignature:"Vasilios N. Katsikis",coverURL:"https://cdn.intechopen.com/books/images_new/2160.jpg",publishedDate:"September 26th 2012",numberOfDownloads:271836,editors:[{id:"12289",title:"Prof.",name:"Vasilios",middleName:"N.",surname:"Katsikis",slug:"vasilios-katsikis",fullName:"Vasilios Katsikis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"3560",title:"Advances in Landscape Architecture",subtitle:null,isOpenForSubmission:!1,hash:"a20614517ec5f7e91188fe8e42832138",slug:"advances-in-landscape-architecture",bookSignature:"Murat Özyavuz",coverURL:"https://cdn.intechopen.com/books/images_new/3560.jpg",publishedDate:"July 1st 2013",numberOfDownloads:243450,editors:[{id:"93073",title:"Dr.",name:"Murat",middleName:null,surname:"Ozyavuz",slug:"murat-ozyavuz",fullName:"Murat Ozyavuz"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10739",title:"Global Decline of Insects",subtitle:null,isOpenForSubmission:!1,hash:"543783652b9092962a8fa4bed38eeb17",slug:"global-decline-of-insects",bookSignature:"Hamadttu Abdel Farag El-Shafie",coverURL:"https://cdn.intechopen.com/books/images_new/10739.jpg",publishedDate:"July 20th 2022",numberOfDownloads:1582,editors:[{id:"192142",title:"Dr.",name:"Hamadttu",middleName:null,surname:"Abdel Farag El-Shafie",slug:"hamadttu-abdel-farag-el-shafie",fullName:"Hamadttu Abdel Farag El-Shafie"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10911",title:"Higher Education",subtitle:"New Approaches to Accreditation, Digitalization, and Globalization in the Age of Covid",isOpenForSubmission:!1,hash:"223a02337498e535e967174c1f648fbc",slug:"higher-education-new-approaches-to-accreditation-digitalization-and-globalization-in-the-age-of-covid",bookSignature:"Lee Waller and Sharon Waller",coverURL:"https://cdn.intechopen.com/books/images_new/10911.jpg",publishedDate:"July 13th 2022",numberOfDownloads:2082,editors:[{id:"263301",title:"Dr.",name:"Lee",middleName:null,surname:"Waller",slug:"lee-waller",fullName:"Lee Waller"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"3568",title:"Recent Advances in Plant in vitro Culture",subtitle:null,isOpenForSubmission:!1,hash:"830bbb601742c85a3fb0eeafe1454c43",slug:"recent-advances-in-plant-in-vitro-culture",bookSignature:"Annarita Leva and Laura M. R. Rinaldi",coverURL:"https://cdn.intechopen.com/books/images_new/3568.jpg",publishedDate:"October 17th 2012",numberOfDownloads:256294,editors:[{id:"142145",title:"Dr.",name:"Annarita",middleName:null,surname:"Leva",slug:"annarita-leva",fullName:"Annarita Leva"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"10808",title:"Current Concepts in Dental Implantology",subtitle:"From Science to Clinical Research",isOpenForSubmission:!1,hash:"4af8830e463f89c57515c2da2b9777b0",slug:"current-concepts-in-dental-implantology-from-science-to-clinical-research",bookSignature:"Dragana Gabrić and Marko Vuletić",coverURL:"https://cdn.intechopen.com/books/images_new/10808.jpg",editedByType:"Edited by",publishedDate:"July 27th 2022",editors:[{id:"26946",title:"Prof.",name:"Dragana",middleName:null,surname:"Gabrić",slug:"dragana-gabric",fullName:"Dragana Gabrić"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11328",title:"Botulinum Toxin",subtitle:"Recent Topics and Applications",isOpenForSubmission:!1,hash:"7dd05a316001cef143e209eda51387a7",slug:"botulinum-toxin-recent-topics-and-applications",bookSignature:"Suna Sabuncuoglu",coverURL:"https://cdn.intechopen.com/books/images_new/11328.jpg",editedByType:"Edited by",publishedDate:"July 27th 2022",editors:[{id:"270856",title:"Associate Prof.",name:"Suna",middleName:null,surname:"Sabuncuoglu",slug:"suna-sabuncuoglu",fullName:"Suna Sabuncuoglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11085",title:"Polycystic Ovary Syndrome",subtitle:"Functional Investigation and Clinical Application",isOpenForSubmission:!1,hash:"3066dd3ff29e1fac072fd60b08d4d3e7",slug:"polycystic-ovary-syndrome-functional-investigation-and-clinical-application",bookSignature:"Zhengchao Wang",coverURL:"https://cdn.intechopen.com/books/images_new/11085.jpg",editedByType:"Edited by",publishedDate:"July 27th 2022",editors:[{id:"204883",title:"Dr.",name:"Zhengchao",middleName:null,surname:"Wang",slug:"zhengchao-wang",fullName:"Zhengchao Wang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10833",title:"Tumor Angiogenesis and Modulators",subtitle:null,isOpenForSubmission:!1,hash:"f29b575c46128b2da061ef7f9bd1070b",slug:"tumor-angiogenesis-and-modulators",bookSignature:"Ke Xu",coverURL:"https://cdn.intechopen.com/books/images_new/10833.jpg",editedByType:"Edited by",publishedDate:"July 27th 2022",editors:[{id:"59529",title:"Dr.",name:"Ke",middleName:null,surname:"Xu",slug:"ke-xu",fullName:"Ke Xu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11356",title:"Molecular Cloning",subtitle:null,isOpenForSubmission:!1,hash:"671c629dd86e97f0fb467b9e70e92296",slug:"molecular-cloning",bookSignature:"Sadık Dincer, Hatice Aysun Mercimek Takcı and Melis Sumengen Ozdenef",coverURL:"https://cdn.intechopen.com/books/images_new/11356.jpg",editedByType:"Edited by",publishedDate:"July 27th 2022",editors:[{id:"188141",title:"Prof.",name:"Sadik",middleName:null,surname:"Dincer",slug:"sadik-dincer",fullName:"Sadik Dincer"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7827",title:"Interpersonal Relationships",subtitle:null,isOpenForSubmission:!1,hash:"ebf41f4d17c75010eb3294cc8cac3d47",slug:"interpersonal-relationships",bookSignature:"Martha Peaslee Levine",coverURL:"https://cdn.intechopen.com/books/images_new/7827.jpg",editedByType:"Edited by",publishedDate:"July 27th 2022",editors:[{id:"186919",title:"Dr.",name:"Martha",middleName:null,surname:"Peaslee Levine",slug:"martha-peaslee-levine",fullName:"Martha Peaslee Levine"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10908",title:"Advances in Decision Making",subtitle:null,isOpenForSubmission:!1,hash:"126486f7f91e18e2e3539a32c38be7b1",slug:"advances-in-decision-making",bookSignature:"Fausto Pedro García Márquez",coverURL:"https://cdn.intechopen.com/books/images_new/10908.jpg",editedByType:"Edited by",publishedDate:"July 27th 2022",editors:[{id:"22844",title:"Prof.",name:"Fausto Pedro",middleName:null,surname:"García Márquez",slug:"fausto-pedro-garcia-marquez",fullName:"Fausto Pedro García Márquez"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10669",title:"Corrosion",subtitle:"Fundamentals and Protection Mechanisms",isOpenForSubmission:!1,hash:"4a76d54f8a40fc2e7002a8d13fd617c1",slug:"corrosion-fundamentals-and-protection-mechanisms",bookSignature:"Fahmina Zafar, Anujit Ghosal and Eram Sharmin",coverURL:"https://cdn.intechopen.com/books/images_new/10669.jpg",editedByType:"Edited by",publishedDate:"July 27th 2022",editors:[{id:"89672",title:"Dr.",name:"Fahmina",middleName:null,surname:"Zafar",slug:"fahmina-zafar",fullName:"Fahmina Zafar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10677",title:"Advanced Topics of Topology",subtitle:null,isOpenForSubmission:!1,hash:"bf964c52f9e653fac20a7fcab58070e5",slug:"advanced-topics-of-topology",bookSignature:"Francisco Bulnes",coverURL:"https://cdn.intechopen.com/books/images_new/10677.jpg",editedByType:"Edited by",publishedDate:"July 27th 2022",editors:[{id:"92918",title:"Dr.",name:"Francisco",middleName:null,surname:"Bulnes",slug:"francisco-bulnes",fullName:"Francisco Bulnes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11195",title:"Recent Advances in Biometrics",subtitle:null,isOpenForSubmission:!1,hash:"2d32e33e0f499cb5241734bb75dd2a83",slug:"recent-advances-in-biometrics",bookSignature:"Muhammad Sarfraz",coverURL:"https://cdn.intechopen.com/books/images_new/11195.jpg",editedByType:"Edited by",publishedDate:"July 27th 2022",editors:[{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"1286",title:"Biomechanics",slug:"biomechanics",parent:{id:"255",title:"Kinematics",slug:"kinematics"},numberOfBooks:1,numberOfSeries:0,numberOfAuthorsAndEditors:32,numberOfWosCitations:4,numberOfCrossrefCitations:19,numberOfDimensionsCitations:23,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicId:"1286",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"6135",title:"Kinematics",subtitle:null,isOpenForSubmission:!1,hash:"64adad9c40c91ce89d9056f769b6cf52",slug:"kinematics",bookSignature:"Efren Gorrostieta Hurtado",coverURL:"https://cdn.intechopen.com/books/images_new/6135.jpg",editedByType:"Edited by",editors:[{id:"38850",title:"Dr.",name:"Efren",middleName:null,surname:"Gorrostieta Hurtado",slug:"efren-gorrostieta-hurtado",fullName:"Efren Gorrostieta Hurtado"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:1,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"57610",doi:"10.5772/intechopen.71417",title:"Forward and Inverse Kinematics Using Pseudoinverse and Transposition Method for Robotic Arm DOBOT",slug:"forward-and-inverse-kinematics-using-pseudoinverse-and-transposition-method-for-robotic-arm-dobot",totalDownloads:2312,totalCrossrefCites:7,totalDimensionsCites:8,abstract:"Kinematic structure of the DOBOT manipulator is presented in this chapter. Joint coordinates and end-effector coordinates of the manipulator are functions of independent coordinates, i.e., joint parameters. This chapter explained forward kinematics task and issue of inverse kinematics task on the structure of the DOBOT manipulator. Linearization of forward kinematic equations is made with usage of Taylor Series for multiple variables. The inversion of Jacobian matrix was used for numerical solution of the inverse kinematics task. The chapter contains analytical equations, which are solution of inverse kinematics task. It should be noted that the analytical solution exists only for simple kinematic structures, for example DOBOT manipulator structure. Subsequently, simulation of the inverse kinematics of the above-mentioned kinematic structure was performed in the Matlab Simulink environment using the SimMechanics toolbox.",book:{id:"6135",slug:"kinematics",title:"Kinematics",fullTitle:"Kinematics"},signatures:"Ondrej Hock and Jozef Šedo",authors:[{id:"208453",title:"Dr.Ing.",name:"Ondrej",middleName:null,surname:"Hock",slug:"ondrej-hock",fullName:"Ondrej Hock"},{id:"209566",title:"Dr.Ing.",name:"Jozef",middleName:null,surname:"Šedo",slug:"jozef-sedo",fullName:"Jozef Šedo"}]},{id:"57605",doi:"10.5772/intechopen.71409",title:"Optimization Approach for Inverse Kinematic Solution",slug:"optimization-approach-for-inverse-kinematic-solution",totalDownloads:1722,totalCrossrefCites:4,totalDimensionsCites:4,abstract:"Inverse kinematics of serial or parallel manipulators can be computed from given Cartesian position and orientation of end effector and reverse of this would yield forward kinematics. Which is nothing but finding out end effector coordinates and angles from given joint angles. Forward kinematics of serial manipulators gives exact solution while inverse kinematics yields number of solutions. The complexity of inverse kinematic solution arises with the increment of degrees of freedom. Therefore it would be desired to adopt optimization techniques. Although the optimization techniques gives number of solution for inverse kinematics problem but it converses the best solution for the minimum function value. The selection of suitable optimization method will provides the global optimization solution, therefore, in this paper proposes quaternion derivation for 5R manipulator inverse kinematic solution which is later compared with teachers learner based optimization (TLBO) and genetic algorithm (GA) for the optimum convergence rate of inverse kinematic solution. An investigation has been made on the accuracies of adopted techniques and total computational time for inverse kinematic evaluations. It is found that TLBO is performing better as compared GA on the basis of fitness function and quaternion algebra gives better computational cost.",book:{id:"6135",slug:"kinematics",title:"Kinematics",fullTitle:"Kinematics"},signatures:"Panchanand Jha and Bibhuti Bhusan Biswal",authors:[{id:"209316",title:"Dr.",name:"Panchanand",middleName:null,surname:"Jha",slug:"panchanand-jha",fullName:"Panchanand Jha"},{id:"209681",title:"Dr.",name:"Bibhuti Bhusan",middleName:null,surname:"Biswal",slug:"bibhuti-bhusan-biswal",fullName:"Bibhuti Bhusan Biswal"}]},{id:"57452",doi:"10.5772/intechopen.71406",title:"Kinematic Performance Measures and Optimization of Parallel Kinematics Manipulators: A Brief Review",slug:"kinematic-performance-measures-and-optimization-of-parallel-kinematics-manipulators-a-brief-review",totalDownloads:1642,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"This chapter covers a number of kinematic performance indices that are instrumental in designing parallel kinematics manipulators. These indices can be used selectively based on manipulator requirements and functionality. This would provide the very practical tool for designers to approach their needs in a very comprehensive fashion. Nevertheless, most applications require a more composite set of requirements that makes optimizing performance more challenging. The later part of this chapter will discuss single-objective and multi-objectives optimization that could handle certain performance indices or a combination of them. A brief description of most common techniques in the literature will be provided.",book:{id:"6135",slug:"kinematics",title:"Kinematics",fullTitle:"Kinematics"},signatures:"Abdur Rosyid, Bashar El-Khasawneh and Anas Alazzam",authors:[{id:"209597",title:"Dr.",name:"Bashar",middleName:null,surname:"El-Khasawneh",slug:"bashar-el-khasawneh",fullName:"Bashar El-Khasawneh"},{id:"217882",title:"Mr.",name:"Abdur",middleName:null,surname:"Rosyid",slug:"abdur-rosyid",fullName:"Abdur Rosyid"},{id:"217884",title:"Dr.",name:"Anas",middleName:null,surname:"Alazzam",slug:"anas-alazzam",fullName:"Anas Alazzam"}]},{id:"57479",doi:"10.5772/intechopen.71444",title:"A New Methodology for Kinematic Parameter Identification in Laser Trackers",slug:"a-new-methodology-for-kinematic-parameter-identification-in-laser-trackers",totalDownloads:1260,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"In recent years, there has been an increasing interest in measurement systems such as laser trackers (LT) for the verification of large-scale parts in the aeronautic, spatial or naval sectors because of their advantages in terms of portability, flexibility, high speed in data acquisition, accuracy, and reliability. These systems present systematic errors caused by geometrical misalignments, environmental conditions, mechanical wear and tear and other unpredictable variables. Different standards such as the ASME B89.4.19 and the VDI 2617-10 suggest tests to calculate the geometric errors of the LT. In this work, we present an alternative calibration method based on a new errors model. The LT can be considered as an open kinematic chain, so it is possible to shape a kinematic model of the LT. Once the kinematic model has been set, the error model is defined. The model has been validated with synthetic data. Then, experimental tests based on the measurement of a mesh of reflectors placed at suitable places for different locations of the LT have been performed to ensure the reliability of the method proposed. A sensitivity analysis shows the best experimental setup to perform a calibration test. The calibration results have been validated with nominal data.",book:{id:"6135",slug:"kinematics",title:"Kinematics",fullTitle:"Kinematics"},signatures:"Ana Cristina Majarena, Javier Conte, Jorge Santolaria and Raquel\nAcero",authors:[{id:"5350",title:"Dr.",name:"Jorge",middleName:null,surname:"Santolaria",slug:"jorge-santolaria",fullName:"Jorge Santolaria"},{id:"153147",title:"Dr.",name:"Ana Cristina",middleName:null,surname:"Majarena Bello",slug:"ana-cristina-majarena-bello",fullName:"Ana Cristina Majarena Bello"},{id:"209623",title:"Mr.",name:"Javier",middleName:null,surname:"Conte",slug:"javier-conte",fullName:"Javier Conte"},{id:"209624",title:"Dr.",name:"Raquel",middleName:null,surname:"Acero",slug:"raquel-acero",fullName:"Raquel Acero"}]},{id:"57491",doi:"10.5772/intechopen.71407",title:"How to Expand the Workspace of Parallel Robots",slug:"how-to-expand-the-workspace-of-parallel-robots",totalDownloads:1416,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"In this chapter, methods for expanding the workspace of parallel robots are introduced. Firstly, methods for expanding the translational workspace of the parallel robot are discussed. The parallel robot has multiple solutions of the inverse and forward displacement analysis. By changing its configurations from one solution to another, the parallel robot can expand its translational workspace. However, conventional nonredundant parallel robot encounters singularity during the mode change. Singularity-free mode changes of the parallel robot by redundant actuation are introduced. Next, methods for expanding the rotational workspace of the parallel robot are shown. In order to achieve the large rotation, some mechanical gimmicks by gears, pulleys, and helical joints have been embedded in the moving part. A novel differential screw-nut mechanism for expanding the rotational workspace of the parallel robot is introduced.",book:{id:"6135",slug:"kinematics",title:"Kinematics",fullTitle:"Kinematics"},signatures:"Takashi Harada",authors:[{id:"57026",title:"Dr.",name:"Takashi",middleName:null,surname:"Harada",slug:"takashi-harada",fullName:"Takashi Harada"}]}],mostDownloadedChaptersLast30Days:[{id:"57435",title:"Kinematic Model for Project Scheduling with Constrained Resources Under Uncertainties",slug:"kinematic-model-for-project-scheduling-with-constrained-resources-under-uncertainties",totalDownloads:1206,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Project management practitioners and researchers recognize that the project scheduling efforts are made based on information with many uncertainties and in an environment with constrained resources. This chapter presents the kinematic model named as Coupled Estimate Technique for project scheduling with constrained resources under uncertainties. The Coupled Estimate Technique provides tools of analytical analysis, given that the modelled duration depends on the planned duration and on the resource variability (aleatory uncertainty), as well as the modelled resource depends on the planned resource and on the duration variability (aleatory uncertainty), and also provides tools of graphical analysis, given that the durations and resources of activities, work packages or phases of the project are represented in the bidimensional graphics. In developing the mathematical formulation of the Coupled Estimate Technique, the project precedence diagram was considered as a kinematic chain of robotic manipulators, which may be in chain configuration open (serial), closed (parallel) and/or hybrid. This chapter describes the resource-constrained project scheduling problem (RCPSP) under uncertainties, identifies the limitations and opportunities in the previous work on planning under uncertainties and presents the fundamentals and method of the kinematic model for project scheduling with constrained resources under uncertainties along with a short example of implementation.",book:{id:"6135",slug:"kinematics",title:"Kinematics",fullTitle:"Kinematics"},signatures:"Giuliani Paulineli Garbi and Francisco José Grandinetti",authors:[{id:"208870",title:"Dr.",name:"Giuliani",middleName:null,surname:"Garbi",slug:"giuliani-garbi",fullName:"Giuliani Garbi"},{id:"221823",title:"Dr.",name:"Francisco José",middleName:null,surname:"Grandinett",slug:"francisco-jose-grandinett",fullName:"Francisco José Grandinett"}]},{id:"57578",title:"Kinematic and Biodynamic Model of the Long Jump Technique",slug:"kinematic-and-biodynamic-model-of-the-long-jump-technique",totalDownloads:1990,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"The main aim of the study was to determine the kinematic model for long jump and define the kinematic and dynamic parameters of an elite long jumper’s technique. The theoretical model was based on real data where the jumper was defined with a joint mass point. In view of certain previous similar studies, our study identified kinematic and dynamic parameters directly without using the inverse mechanics method. The analysis was made on two jumps of the top level athlete G.C., who won the bronze medallion in long jump at the World Championships in Seville. The kinematic parameters of the take-off, flight and landing were measured with a 3-D video ARIEL system (Ariel Dynamics Inc., USA). The dynamic characteristics of take-off in the X, Y and Z axes were registered with a force-platform (KISTLER-9287), which was installed immediately prior the take-off board. The take-off efficiency was defined best by the following parameters: horizontal velocity, VXTO—8.10 m s−1; vertical velocity, VYTO—3.90 m s−1; angle of projection, PATO—24.1°; duration of compression phase, TDMKF—84 ms, duration of lift phase, MKFTO—43 ms and maximal force in Y-vertical axis, FYMAX—5132 N. An important factor of a rational technique of long jump is also the landing, which is defined by the landing distance and fall-back distance. The efficiency of the landing depended on the landing distance L3—0.63 m and fall-back distance LFB, which amounted to 0.15 m.",book:{id:"6135",slug:"kinematics",title:"Kinematics",fullTitle:"Kinematics"},signatures:"Milan Čoh, Milan Žvan and Otmar Kugovnik",authors:[{id:"208530",title:"Ph.D.",name:"Milan",middleName:null,surname:"Čoh",slug:"milan-coh",fullName:"Milan Čoh"}]},{id:"57610",title:"Forward and Inverse Kinematics Using Pseudoinverse and Transposition Method for Robotic Arm DOBOT",slug:"forward-and-inverse-kinematics-using-pseudoinverse-and-transposition-method-for-robotic-arm-dobot",totalDownloads:2308,totalCrossrefCites:7,totalDimensionsCites:8,abstract:"Kinematic structure of the DOBOT manipulator is presented in this chapter. Joint coordinates and end-effector coordinates of the manipulator are functions of independent coordinates, i.e., joint parameters. This chapter explained forward kinematics task and issue of inverse kinematics task on the structure of the DOBOT manipulator. Linearization of forward kinematic equations is made with usage of Taylor Series for multiple variables. The inversion of Jacobian matrix was used for numerical solution of the inverse kinematics task. The chapter contains analytical equations, which are solution of inverse kinematics task. It should be noted that the analytical solution exists only for simple kinematic structures, for example DOBOT manipulator structure. Subsequently, simulation of the inverse kinematics of the above-mentioned kinematic structure was performed in the Matlab Simulink environment using the SimMechanics toolbox.",book:{id:"6135",slug:"kinematics",title:"Kinematics",fullTitle:"Kinematics"},signatures:"Ondrej Hock and Jozef Šedo",authors:[{id:"208453",title:"Dr.Ing.",name:"Ondrej",middleName:null,surname:"Hock",slug:"ondrej-hock",fullName:"Ondrej Hock"},{id:"209566",title:"Dr.Ing.",name:"Jozef",middleName:null,surname:"Šedo",slug:"jozef-sedo",fullName:"Jozef Šedo"}]},{id:"57605",title:"Optimization Approach for Inverse Kinematic Solution",slug:"optimization-approach-for-inverse-kinematic-solution",totalDownloads:1721,totalCrossrefCites:4,totalDimensionsCites:4,abstract:"Inverse kinematics of serial or parallel manipulators can be computed from given Cartesian position and orientation of end effector and reverse of this would yield forward kinematics. Which is nothing but finding out end effector coordinates and angles from given joint angles. Forward kinematics of serial manipulators gives exact solution while inverse kinematics yields number of solutions. The complexity of inverse kinematic solution arises with the increment of degrees of freedom. Therefore it would be desired to adopt optimization techniques. Although the optimization techniques gives number of solution for inverse kinematics problem but it converses the best solution for the minimum function value. The selection of suitable optimization method will provides the global optimization solution, therefore, in this paper proposes quaternion derivation for 5R manipulator inverse kinematic solution which is later compared with teachers learner based optimization (TLBO) and genetic algorithm (GA) for the optimum convergence rate of inverse kinematic solution. An investigation has been made on the accuracies of adopted techniques and total computational time for inverse kinematic evaluations. It is found that TLBO is performing better as compared GA on the basis of fitness function and quaternion algebra gives better computational cost.",book:{id:"6135",slug:"kinematics",title:"Kinematics",fullTitle:"Kinematics"},signatures:"Panchanand Jha and Bibhuti Bhusan Biswal",authors:[{id:"209316",title:"Dr.",name:"Panchanand",middleName:null,surname:"Jha",slug:"panchanand-jha",fullName:"Panchanand Jha"},{id:"209681",title:"Dr.",name:"Bibhuti Bhusan",middleName:null,surname:"Biswal",slug:"bibhuti-bhusan-biswal",fullName:"Bibhuti Bhusan Biswal"}]},{id:"57413",title:"Optimization of Single-Sided Lapping Kinematics Based on Statistical Analysis of Abrasive Particles Trajectories",slug:"optimization-of-single-sided-lapping-kinematics-based-on-statistical-analysis-of-abrasive-particles-",totalDownloads:1426,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"The chapter presents the influence of selected kinematic parameters on the geometrical results of the single-sided lapping process. The optimization of these parameters is aimed at improving the quality and flatness of the machined surfaces. The uniformity of tool wear was assumed as main optimization criterion. Lapping plate wear model was created and in detail was analyzed. A Matlab program was designed to simulate the abrasive particles trajectories and to count their distribution. In addition, the influence of additional guiding movements of the conditioning ring has been verified and the idea of a flexible single-sided lapping system assisted with a robot, which ensures the optimal constant wear over the diameter was presented.",book:{id:"6135",slug:"kinematics",title:"Kinematics",fullTitle:"Kinematics"},signatures:"Adam Barylski and Norbert Piotrowski",authors:[{id:"208566",title:"M.Sc.",name:"Norbert",middleName:null,surname:"Piotrowski",slug:"norbert-piotrowski",fullName:"Norbert Piotrowski"},{id:"209144",title:"Prof.",name:"Adam",middleName:null,surname:"Barylski",slug:"adam-barylski",fullName:"Adam Barylski"}]}],onlineFirstChaptersFilter:{topicId:"1286",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:141,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:124,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343",scope:"Biomedical Engineering is one of the fastest-growing interdisciplinary branches of science and industry. The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. This series is intended for doctors, engineers, and scientists involved in biomedical engineering or those wanting to start working in this field.",coverUrl:"https://cdn.intechopen.com/series/covers/7.jpg",latestPublicationDate:"August 14th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:12,editor:{id:"50150",title:"Prof.",name:"Robert",middleName:null,surname:"Koprowski",slug:"robert-koprowski",fullName:"Robert Koprowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTYNQA4/Profile_Picture_1630478535317",biography:"Robert Koprowski, MD (1997), PhD (2003), Habilitation (2015), is an employee of the University of Silesia, Poland, Institute of Computer Science, Department of Biomedical Computer Systems. For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:5,paginationItems:[{id:"91",title:"Sustainable Economy and Fair Society",coverUrl:"https://cdn.intechopen.com/series_topics/covers/91.jpg",isOpenForSubmission:!0,editor:{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo",profilePictureURL:"https://mts.intechopen.com/storage/users/181603/images/system/181603.jpg",biography:"Antonella Petrillo, Ph.D., is a professor in the Department of Engineering, University of Naples “Parthenope,” Italy. She received her Ph.D. in Mechanical Engineering from the University of Cassino and Southern Lazio, Italy. Her research interests include multi-criteria decision analysis, industrial plants, logistics, manufacturing, and safety. She serves as an associate editor for the International Journal of the Analytic Hierarchy Process and is an editorial board member for several other journals. She is also a member of the Analytic Hierarchy Process (AHP) Academy.",institutionString:"Parthenope University of Naples",institution:{name:"Parthenope University of Naples",institutionURL:null,country:{name:"Italy"}}},editorTwo:null,editorThree:null},{id:"92",title:"Health and Wellbeing",coverUrl:"https://cdn.intechopen.com/series_topics/covers/92.jpg",isOpenForSubmission:!0,editor:{id:"348225",title:"Prof.",name:"Ann",middleName:null,surname:"Hemingway",slug:"ann-hemingway",fullName:"Ann Hemingway",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035LZFoQAO/Profile_Picture_2022-04-11T14:55:40.jpg",biography:"Professor Hemingway is a public health researcher, Bournemouth University, undertaking international and UK research focused on reducing inequalities in health outcomes for marginalised and excluded populations and more recently focused on equine assisted interventions.",institutionString:null,institution:{name:"Bournemouth University",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null},{id:"93",title:"Inclusivity and Social Equity",coverUrl:"https://cdn.intechopen.com/series_topics/covers/93.jpg",isOpenForSubmission:!0,editor:{id:"210060",title:"Prof. Dr.",name:"Ebba",middleName:null,surname:"Ossiannilsson",slug:"ebba-ossiannilsson",fullName:"Ebba Ossiannilsson",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6LkBQAU/Profile_Picture_2022-02-28T13:31:48.png",biography:"Professor Dr. Ebba Ossiannilsson is an independent researcher, expert, consultant, quality auditor and influencer in the fields of open, flexible online and distance learning (OFDL) and the 'new normal'. Her focus is on quality, innovation, leadership, and personalised learning. She works primarily at the strategic and policy levels, both nationally and internationally, and with key international organisations. She is committed to promoting and improving OFDL in the context of SDG4 and the future of education. Ossiannilsson has more than 20 years of experience in her current field, but more than 40 years in the education sector. She works as a reviewer and expert for the European Commission and collaborates with the Joint Research Centre for Quality in Open Education. Ossiannilsson also collaborates with ITCILO and ICoBC (International Council on Badges and Credentials). She is a member of the ICDE Board of Directors and has previously served on the boards of EDEN and EUCEN. Ossiannilsson is a quality expert and reviewer for ICDE, EDEN and the EADTU. She chairs the ICDE OER Advocacy Committee and is a member of the ICDE Quality Network. She is regularly invited as a keynote speaker at conferences. She is a guest editor for several special issues and a member of the editorial board of several scientific journals. She has published more than 200 articles and is currently working on book projects in the field of OFDL. Ossiannilsson is a visiting professor at several international universities and was recently appointed Professor and Research Fellow at Victoria University of Wellington, NZ. Ossiannilsson has been awarded the following fellowships: EDEN Fellows, EDEN Council of Fellows, and Open Education Europe. She is a ICDE OER Ambassador, Open Education Europe Ambassador, GIZ Ambassador for Quality in Digital Learning, and part of the Globe-Community of Digital Learning and Champion of SPARC Europe. On a national level, she is a quality developer at the Swedish Institute for Standards (SIS) and for ISO. She is a member of the Digital Skills and Jobs Coalition Sweden and Vice President of the Swedish Association for Distance Education. She is currently working on a government initiative on quality in distance education at the National Council for Higher Education. She holds a Ph.D. from the University of Oulu, Finland.",institutionString:"Swedish Association for Distance Education, Sweden",institution:null},editorTwo:null,editorThree:null},{id:"94",title:"Climate Change and Environmental Sustainability",coverUrl:"https://cdn.intechopen.com/series_topics/covers/94.jpg",isOpenForSubmission:!0,editor:{id:"61855",title:"Dr.",name:"Yixin",middleName:null,surname:"Zhang",slug:"yixin-zhang",fullName:"Yixin Zhang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYWJgQAO/Profile_Picture_2022-06-09T11:36:35.jpg",biography:"Professor Yixin Zhang is an aquatic ecologist with over 30 years of research and teaching experience in three continents (Asia, Europe, and North America) in Stream Ecology, Riparian Ecology, Urban Ecology, and Ecosystem Restoration and Aquatic Conservation, Human-Nature Interactions and Sustainability, Urbanization Impact on Aquatic Ecosystems. He got his Ph.D. in Animal Ecology at Umeå University in Sweden in 1998. He conducted postdoc research in stream ecology at the University of California at Santa Barbara in the USA. After that, he was a postdoc research fellow at the University of British Columbia in Canada to do research on large-scale stream experimental manipulation and watershed ecological survey in temperate rainforests of BC. He was a faculty member at the University of Hong Kong to run ecological research projects on aquatic insects, fishes, and newts in Tropical Asian streams. He also conducted research in streams, rivers, and caves in Texas, USA, to study the ecology of macroinvertebrates, big-claw river shrimp, fish, turtles, and bats. Current research interests include trophic flows across ecosystems; watershed impacts of land-use change on biodiversity and ecosystem functioning; ecological civilization and water resource management; urban ecology and urban/rural sustainable development.",institutionString:null,institution:{name:"Soochow University",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null},{id:"95",title:"Urban Planning and Environmental Management",coverUrl:"https://cdn.intechopen.com/series_topics/covers/95.jpg",isOpenForSubmission:!0,editor:{id:"181079",title:"Dr.",name:"Christoph",middleName:null,surname:"Lüthi",slug:"christoph-luthi",fullName:"Christoph Lüthi",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRHSqQAO/Profile_Picture_2022-04-12T15:51:33.png",biography:"Dr. Christoph Lüthi is an urban infrastructure planner with over 25 years of experience in planning and design of urban infrastructure in middle and low-income countries. He holds a Master’s Degree in Urban Development Planning from the University College of London (UCL), and a Ph.D. in Urban Planning & Engineering from TU Berlin. He has conducted applied research on urban planning and infrastructure issues in over 20 countries in Africa and Asia. In 2005 he joined Eawag-Sandec as Leader of the Strategic Environmental Sanitation Planning Group. Since 2015 he heads the research department Sanitation, Water and Solid Waste for Development (Sandec) at the Swiss Federal Institute of Aquatic Research and Technology (Eawag).",institutionString:"Swiss Federal Institute of Aquatic Science and Technology, Switzerland",institution:{name:"Swiss Federal Institute of Aquatic Science and Technology",institutionURL:null,country:{name:"Switzerland"}}},editorTwo:{id:"290571",title:"Dr.",name:"Rui Alexandre",middleName:null,surname:"Castanho",slug:"rui-alexandre-castanho",fullName:"Rui Alexandre Castanho",profilePictureURL:"https://mts.intechopen.com/storage/users/290571/images/system/290571.jpg",biography:"Rui Alexandre Castanho has a master\\'s degree in Planning, Audit, and Control in Urban Green Spaces and an international Ph.D. in Sustainable Planning in Borderlands. Currently, he is a professor at WSB University, Poland, and a visiting professor at the University of Johannesburg, South Africa. Dr. Castanho is a post-doc researcher on the GREAT Project, University of Azores, Ponta Delgada, Portugal. He collaborates with the Environmental Resources Analysis Research Group (ARAM), University of Extremadura (UEx), Spain; VALORIZA - Research Center for the Enhancement of Endogenous Resources, Polytechnic Institute of Portalegre (IPP), Portugal; Centre for Tourism Research, Development and Innovation (CITUR), Madeira, Portugal; and AQUAGEO Research Group, University of Campinas (UNICAMP), Brazil.",institutionString:"University of Johannesburg, South Africa and WSB University, Poland",institution:{name:"University of Johannesburg",institutionURL:null,country:{name:"South Africa"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:9,paginationItems:[{id:"82936",title:"Soil Degradation Processes Linked to Long-Term Forest-Type Damage",doi:"10.5772/intechopen.106390",signatures:"Pavel Samec, Aleš Kučera and Gabriela Tomášová",slug:"soil-degradation-processes-linked-to-long-term-forest-type-damage",totalDownloads:3,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Forest Degradation Under Global Change",coverURL:"https://cdn.intechopen.com/books/images_new/11457.jpg",subseries:{id:"94",title:"Climate Change and Environmental Sustainability"}}},{id:"82777",title:"Sustainability and Social Investment: Community Microhydropower Systems in the Dominican Republic",doi:"10.5772/intechopen.105995",signatures:"Michela Izzo, Alberto Sánchez and Rafael Fonseca",slug:"sustainability-and-social-investment-community-microhydropower-systems-in-the-dominican-republic",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Globalization and Sustainability - Recent Advances, New Perspectives and Emerging Issues",coverURL:"https://cdn.intechopen.com/books/images_new/11476.jpg",subseries:{id:"91",title:"Sustainable Economy and Fair Society"}}},{id:"82387",title:"Kept Promises? The Evolution of the EU Financial Contribution to Climate Change",doi:"10.5772/intechopen.105541",signatures:"Cecilia Camporeale, Roberto Del Ciello and Mario Jorizzo",slug:"kept-promises-the-evolution-of-the-eu-financial-contribution-to-climate-change",totalDownloads:11,totalCrossrefCites:0,totalDimensionsCites:0,authors:[{name:"Mario",surname:"Jorizzo"},{name:"Cecilia",surname:"Camporeale"},{name:"ROBERTO",surname:"DEL CIELLO"}],book:{title:"Globalization and Sustainability - Recent Advances, New Perspectives and Emerging Issues",coverURL:"https://cdn.intechopen.com/books/images_new/11476.jpg",subseries:{id:"91",title:"Sustainable Economy and Fair Society"}}},{id:"82524",title:"Italy’s Small Exporting Companies: Globalization and Sustainability Issues",doi:"10.5772/intechopen.105542",signatures:"Roberta Pace and Francesca Mandanici",slug:"italy-s-small-exporting-companies-globalization-and-sustainability-issues",totalDownloads:13,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Globalization and Sustainability - Recent Advances, New Perspectives and Emerging Issues",coverURL:"https://cdn.intechopen.com/books/images_new/11476.jpg",subseries:{id:"91",title:"Sustainable Economy and Fair Society"}}}]},overviewPagePublishedBooks:{paginationCount:1,paginationItems:[{type:"book",id:"10897",title:"Food Systems Resilience",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/10897.jpg",slug:"food-systems-resilience",publishedDate:"July 13th 2022",editedByType:"Edited by",bookSignature:"Ana I. Ribeiro-Barros, Daniel S. Tevera, Luís F. Goulao and Lucas D. Tivana",hash:"ae9dd92f53433e4607f1db188dc649b4",volumeInSeries:1,fullTitle:"Food Systems Resilience",editors:[{id:"171036",title:"Dr.",name:"Ana I.",middleName:null,surname:"Ribeiro-Barros",slug:"ana-i.-ribeiro-barros",fullName:"Ana I. Ribeiro-Barros",profilePictureURL:"https://mts.intechopen.com/storage/users/171036/images/system/171036.jpg",biography:"Ana I. Ribeiro-Barros, Ph.D., is the director of the Tropical College, University of Lisbon (ULisboa). She obtained a Ph.D. in Plant Molecular Biology from Wageningen University, the Netherlands. She is also a senior researcher, head of the lab, and professor at the School of Agriculture, ULisboa, and an invited professor at Nova University Lisbon (NOVA), Eduardo Mondlane University (UEM), and Gorongosa National Park (GNP). She is a member of the Coordination and Scientific Committees of the doctoral program “Tropical Knowledge and Management” (NOVA), Master in Biotechnology (UEM), and Master in Conservation Biology (GNP); and a national expert for Food and Nutrition Security and Sustainable Agriculture - High-Level Policy Dialogue EU-Africa. Her research expertise and interests are centered on biodiversity, environmental sustainability, agro-ecological approaches, and food and nutritional security.",institutionString:"University of Lisbon",institution:{name:"University of Lisbon",institutionURL:null,country:{name:"Portugal"}}}]}]},openForSubmissionBooks:{paginationCount:2,paginationItems:[{id:"12141",title:"Leadership - Advancing Great Leadership Practices and Good Leaders",coverURL:"https://cdn.intechopen.com/books/images_new/12141.jpg",hash:"85f77453916f1d80d80d88ee4fd2f2d1",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"July 1st 2022",isOpenForSubmission:!0,editors:[{id:"420133",title:"Dr.",name:"Joseph",surname:"Crawford",slug:"joseph-crawford",fullName:"Joseph Crawford"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"12139",title:"Global Market and Trade",coverURL:"https://cdn.intechopen.com/books/images_new/12139.jpg",hash:"fa34af07c3a9657fa670404202f8cba5",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"July 21st 2022",isOpenForSubmission:!0,editors:[{id:"243649",title:"Dr.Ing.",name:"Ireneusz",surname:"Miciuła",slug:"ireneusz-miciula",fullName:"Ireneusz Miciuła"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},onlineFirstChapters:{paginationCount:49,paginationItems:[{id:"83087",title:"Role of Cellular Responses in Periodontal Tissue Destruction",doi:"10.5772/intechopen.106645",signatures:"Nam Cong-Nhat Huynh",slug:"role-of-cellular-responses-in-periodontal-tissue-destruction",totalDownloads:1,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Periodontology - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11566.jpg",subseries:{id:"1",title:"Oral Health"}}},{id:"83073",title:"Dental and Orofacial Trauma Impacts on Oral-Health-Related—Quality of Life in Children: Low- and Middle-Income Countries",doi:"10.5772/intechopen.105845",signatures:"Yolanda Malele-Kolisa, Nazia Khan, Mpho P. Molete, Maphefo D. Thekiso and Mzubanzi Mabongo",slug:"dental-and-orofacial-trauma-impacts-on-oral-health-related-quality-of-life-in-children-low-and-middl",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Dental Trauma",coverURL:"https://cdn.intechopen.com/books/images_new/11567.jpg",subseries:{id:"2",title:"Prosthodontics and Implant Dentistry"}}},{id:"82938",title:"Trauma from Occlusion: Practical Management Guidelines",doi:"10.5772/intechopen.105960",signatures:"Prashanth Shetty, Shweta Hegde, Shubham Chelkar, Rahul Chaturvedi, Shruti Pochhi, Aakanksha Shrivastava, Dudala Lakshmi, Shreya Mukherjee, Pankaj Bajaj and Shahzada Asif Raza",slug:"trauma-from-occlusion-practical-management-guidelines",totalDownloads:14,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Dental Trauma",coverURL:"https://cdn.intechopen.com/books/images_new/11567.jpg",subseries:{id:"2",title:"Prosthodontics and Implant Dentistry"}}},{id:"82654",title:"Atraumatic Restorative Treatment: More than a Minimally Invasive Approach?",doi:"10.5772/intechopen.105623",signatures:"Manal A. Ablal",slug:"atraumatic-restorative-treatment-more-than-a-minimally-invasive-approach",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Dental Caries - The Selection of Restoration Methods and Restorative Materials",coverURL:"https://cdn.intechopen.com/books/images_new/11565.jpg",subseries:{id:"1",title:"Oral Health"}}},{id:"82608",title:"Early Management of Dental Trauma in the Era of COVID-19",doi:"10.5772/intechopen.105992",signatures:"Khairul Bariah Chi Adam, Haszelini Hassan, Pram Kumar Subramaniam, Izzati Nabilah Ismail, Nor Adilah Harun and Naziyah Shaban Mustafa",slug:"early-management-of-dental-trauma-in-the-era-of-covid-19",totalDownloads:3,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Dental Trauma",coverURL:"https://cdn.intechopen.com/books/images_new/11567.jpg",subseries:{id:"2",title:"Prosthodontics and Implant Dentistry"}}},{id:"82767",title:"Teeth Avulsion",doi:"10.5772/intechopen.105846",signatures:"Manal Abdalla Eltahir, Randa Fath Elrahman Ibrahim and Hanan Alharbi",slug:"teeth-avulsion",totalDownloads:21,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Dental Trauma",coverURL:"https://cdn.intechopen.com/books/images_new/11567.jpg",subseries:{id:"2",title:"Prosthodontics and Implant Dentistry"}}},{id:"82735",title:"The Influence of Salivary pH on the Prevalence of Dental Caries",doi:"10.5772/intechopen.106154",signatures:"Laura-Cristina Rusu, Alexandra Roi, Ciprian-Ioan Roi, Codruta Victoria Tigmeanu and Lavinia Cosmina Ardelean",slug:"the-influence-of-salivary-ph-on-the-prevalence-of-dental-caries",totalDownloads:12,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Dental Caries - The Selection of Restoration Methods and Restorative Materials",coverURL:"https://cdn.intechopen.com/books/images_new/11565.jpg",subseries:{id:"1",title:"Oral Health"}}},{id:"82288",title:"Dental Emergency and Conditions",doi:"10.5772/intechopen.105495",signatures:"Navneet Kaur",slug:"dental-emergency-and-conditions",totalDownloads:12,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Dental Trauma",coverURL:"https://cdn.intechopen.com/books/images_new/11567.jpg",subseries:{id:"2",title:"Prosthodontics and Implant Dentistry"}}},{id:"81961",title:"Antioxidants as an Adjuncts to Periodontal Therapy",doi:"10.5772/intechopen.105016",signatures:"Sura Dakhil Jassim and Ali Abbas Abdulkareem",slug:"antioxidants-as-an-adjuncts-to-periodontal-therapy",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Dental Trauma",coverURL:"https://cdn.intechopen.com/books/images_new/11567.jpg",subseries:{id:"2",title:"Prosthodontics and Implant Dentistry"}}},{id:"82357",title:"Caries Management Aided by Fluorescence-Based Devices",doi:"10.5772/intechopen.105567",signatures:"Atena Galuscan, Daniela Jumanca and Aurora Doris Fratila",slug:"caries-management-aided-by-fluorescence-based-devices",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Dental Caries - The Selection of Restoration Methods and Restorative Materials",coverURL:"https://cdn.intechopen.com/books/images_new/11565.jpg",subseries:{id:"1",title:"Oral Health"}}}]},subseriesFiltersForOFChapters:[{caption:"Prosthodontics and Implant Dentistry",value:2,count:23,group:"subseries"},{caption:"Oral Health",value:1,count:26,group:"subseries"}],publishedBooks:{paginationCount:9,paginationItems:[{type:"book",id:"10808",title:"Current Concepts in Dental Implantology",subtitle:"From Science to Clinical Research",coverURL:"https://cdn.intechopen.com/books/images_new/10808.jpg",slug:"current-concepts-in-dental-implantology-from-science-to-clinical-research",publishedDate:"July 27th 2022",editedByType:"Edited by",bookSignature:"Dragana Gabrić and Marko Vuletić",hash:"4af8830e463f89c57515c2da2b9777b0",volumeInSeries:11,fullTitle:"Current Concepts in Dental Implantology - From Science to Clinical Research",editors:[{id:"26946",title:"Prof.",name:"Dragana",middleName:null,surname:"Gabrić",slug:"dragana-gabric",fullName:"Dragana Gabrić",profilePictureURL:"https://mts.intechopen.com/storage/users/26946/images/system/26946.png",institutionString:"University of Zagreb",institution:{name:"University of Zagreb",institutionURL:null,country:{name:"Croatia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9493",title:"Periodontology",subtitle:"Fundamentals and Clinical Features",coverURL:"https://cdn.intechopen.com/books/images_new/9493.jpg",slug:"periodontology-fundamentals-and-clinical-features",publishedDate:"February 16th 2022",editedByType:"Edited by",bookSignature:"Petra Surlin",hash:"dfe986c764d6c82ae820c2df5843a866",volumeInSeries:8,fullTitle:"Periodontology - Fundamentals and Clinical Features",editors:[{id:"171921",title:"Prof.",name:"Petra",middleName:null,surname:"Surlin",slug:"petra-surlin",fullName:"Petra Surlin",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:"University of Medicine and Pharmacy of Craiova",institution:{name:"University of Medicine and Pharmacy of Craiova",institutionURL:null,country:{name:"Romania"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9588",title:"Clinical Concepts and Practical Management Techniques in Dentistry",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/9588.jpg",slug:"clinical-concepts-and-practical-management-techniques-in-dentistry",publishedDate:"February 9th 2022",editedByType:"Edited by",bookSignature:"Aneesa Moolla",hash:"42deab8d3bcf3edf64d1d9028d42efd1",volumeInSeries:7,fullTitle:"Clinical Concepts and Practical Management Techniques in Dentistry",editors:[{id:"318170",title:"Dr.",name:"Aneesa",middleName:null,surname:"Moolla",slug:"aneesa-moolla",fullName:"Aneesa Moolla",profilePictureURL:"https://mts.intechopen.com/storage/users/318170/images/system/318170.png",institutionString:"University of the Witwatersrand",institution:{name:"University of the Witwatersrand",institutionURL:null,country:{name:"South Africa"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"8202",title:"Periodontal Disease",subtitle:"Diagnostic and Adjunctive Non-surgical Considerations",coverURL:"https://cdn.intechopen.com/books/images_new/8202.jpg",slug:"periodontal-disease-diagnostic-and-adjunctive-non-surgical-considerations",publishedDate:"February 5th 2020",editedByType:"Edited by",bookSignature:"Nermin Mohammed Ahmed Yussif",hash:"0aee9799da7db2c732be44dd8fed16d8",volumeInSeries:6,fullTitle:"Periodontal Disease - Diagnostic and Adjunctive Non-surgical Considerations",editors:[{id:"210472",title:"Dr.",name:"Nermin",middleName:"Mohammed Ahmed",surname:"Yussif",slug:"nermin-yussif",fullName:"Nermin Yussif",profilePictureURL:"https://mts.intechopen.com/storage/users/210472/images/system/210472.jpg",institutionString:"MSA University",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"8837",title:"Human Teeth",subtitle:"Key Skills and Clinical Illustrations",coverURL:"https://cdn.intechopen.com/books/images_new/8837.jpg",slug:"human-teeth-key-skills-and-clinical-illustrations",publishedDate:"January 22nd 2020",editedByType:"Edited by",bookSignature:"Zühre Akarslan and Farid Bourzgui",hash:"ac055c5801032970123e0a196c2e1d32",volumeInSeries:5,fullTitle:"Human Teeth - Key Skills and Clinical Illustrations",editors:[{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",institutionString:"Gazi University",institution:{name:"Gazi University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:{id:"52177",title:"Prof.",name:"Farid",middleName:null,surname:"Bourzgui",slug:"farid-bourzgui",fullName:"Farid Bourzgui",profilePictureURL:"https://mts.intechopen.com/storage/users/52177/images/system/52177.png",biography:"Prof. Farid Bourzgui obtained his DMD and his DNSO option in Orthodontics at the School of Dental Medicine, Casablanca Hassan II University, Morocco, in 1995 and 2000, respectively. Currently, he is a professor of Orthodontics. He holds a Certificate of Advanced Study type A in Technology of Biomaterials used in Dentistry (1995); Certificate of Advanced Study type B in Dento-Facial Orthopaedics (1997) from the Faculty of Dental Surgery, University Denis Diderot-Paris VII, France; Diploma of Advanced Study (DESA) in Biocompatibility of Biomaterials from the Faculty of Medicine and Pharmacy of Casablanca (2002); Certificate of Clinical Occlusodontics from the Faculty of Dentistry of Casablanca (2004); University Diploma of Biostatistics and Perceptual Health Measurement from the Faculty of Medicine and Pharmacy of Casablanca (2011); and a University Diploma of Pedagogy of Odontological Sciences from the Faculty of Dentistry of Casablanca (2013). He is the author of several scientific articles, book chapters, and books.",institutionString:"University of Hassan II Casablanca",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"7",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"University of Hassan II Casablanca",institutionURL:null,country:{name:"Morocco"}}},equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7060",title:"Gingival Disease",subtitle:"A Professional Approach for Treatment and Prevention",coverURL:"https://cdn.intechopen.com/books/images_new/7060.jpg",slug:"gingival-disease-a-professional-approach-for-treatment-and-prevention",publishedDate:"October 23rd 2019",editedByType:"Edited by",bookSignature:"Alaa Eddin Omar Al Ostwani",hash:"b81d39988cba3a3cf746c1616912cf41",volumeInSeries:4,fullTitle:"Gingival Disease - A Professional Approach for Treatment and Prevention",editors:[{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7572",title:"Trauma in Dentistry",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7572.jpg",slug:"trauma-in-dentistry",publishedDate:"July 3rd 2019",editedByType:"Edited by",bookSignature:"Serdar Gözler",hash:"7cb94732cfb315f8d1e70ebf500eb8a9",volumeInSeries:3,fullTitle:"Trauma in Dentistry",editors:[{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7139",title:"Current Approaches in Orthodontics",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7139.jpg",slug:"current-approaches-in-orthodontics",publishedDate:"April 10th 2019",editedByType:"Edited by",bookSignature:"Belma Işık Aslan and Fatma Deniz Uzuner",hash:"2c77384eeb748cf05a898d65b9dcb48a",volumeInSeries:2,fullTitle:"Current Approaches in Orthodontics",editors:[{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"6668",title:"Dental Caries",subtitle:"Diagnosis, Prevention and Management",coverURL:"https://cdn.intechopen.com/books/images_new/6668.jpg",slug:"dental-caries-diagnosis-prevention-and-management",publishedDate:"September 19th 2018",editedByType:"Edited by",bookSignature:"Zühre Akarslan",hash:"b0f7667770a391f772726c3013c1b9ba",volumeInSeries:1,fullTitle:"Dental Caries - Diagnosis, Prevention and Management",editors:[{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",institutionString:"Gazi University",institution:{name:"Gazi University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Prosthodontics and Implant Dentistry",value:2,count:3},{group:"subseries",caption:"Oral Health",value:1,count:6}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:3},{group:"publicationYear",caption:"2020",value:2020,count:2},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:250,paginationItems:[{id:"274452",title:"Dr.",name:"Yousif",middleName:"Mohamed",surname:"Abdallah",slug:"yousif-abdallah",fullName:"Yousif Abdallah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274452/images/8324_n.jpg",biography:"I certainly enjoyed my experience in Radiotherapy and Nuclear Medicine, particularly it has been in different institutions and hospitals with different Medical Cultures and allocated resources. 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:{name:"University of Silesia",country:{name:"Poland"}}},{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:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:{name:"Medical University Plovdiv",country:{name:"Bulgaria"}}},{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. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"243698",title:"Dr.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:null,institution:null},{id:"7227",title:"Dr.",name:"Hiroaki",middleName:null,surname:"Matsui",slug:"hiroaki-matsui",fullName:"Hiroaki Matsui",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Tokyo",country:{name:"Japan"}}},{id:"312999",title:"Dr.",name:"Bernard O.",middleName:null,surname:"Asimeng",slug:"bernard-o.-asimeng",fullName:"Bernard O. Asimeng",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"318905",title:"Prof.",name:"Elvis",middleName:"Kwason",surname:"Tiburu",slug:"elvis-tiburu",fullName:"Elvis Tiburu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"336193",title:"Dr.",name:"Abdullah",middleName:null,surname:"Alamoudi",slug:"abdullah-alamoudi",fullName:"Abdullah Alamoudi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"318657",title:"MSc.",name:"Isabell",middleName:null,surname:"Steuding",slug:"isabell-steuding",fullName:"Isabell Steuding",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"318656",title:"BSc.",name:"Peter",middleName:null,surname:"Kußmann",slug:"peter-kussmann",fullName:"Peter Kußmann",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}}]}},subseries:{item:{id:"92",type:"subseries",title:"Health and Wellbeing",keywords:"Ecology, Ecological, Nature, Health, Wellbeing, Health Production",scope:"\r\n\tSustainable approaches to health and wellbeing in our COVID 19 recovery needs to focus on ecological approaches that prioritize our relationships with each other, and include engagement with nature, the arts and our heritage. This will ensure that we discover ways to live in our world that allows us and other beings to flourish. We can no longer rely on medicalized approaches to health that wait for people to become ill before attempting to treat them. We need to live in harmony with nature and rediscover the beauty and balance in our everyday lives and surroundings, which contribute to our well-being and that of all other creatures on the planet. This topic will provide insights and knowledge into how to achieve this change in health care that is based on ecologically sustainable practices.
",coverUrl:"https://cdn.intechopen.com/series_topics/covers/92.jpg",hasOnlineFirst:!1,hasPublishedBooks:!1,annualVolume:11976,editor:{id:"348225",title:"Prof.",name:"Ann",middleName:null,surname:"Hemingway",slug:"ann-hemingway",fullName:"Ann Hemingway",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035LZFoQAO/Profile_Picture_2022-04-11T14:55:40.jpg",biography:"Professor Hemingway is a public health researcher, Bournemouth University, undertaking international and UK research focused on reducing inequalities in health outcomes for marginalised and excluded populations and more recently focused on equine assisted interventions.",institutionString:null,institution:{name:"Bournemouth University",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null,series:{id:"24",title:"Sustainable Development",doi:"10.5772/intechopen.100361",issn:"2753-6580"},editorialBoard:[{id:"169536",title:"Dr.",name:"David",middleName:null,surname:"Claborn",slug:"david-claborn",fullName:"David Claborn",profilePictureURL:"https://mts.intechopen.com/storage/users/169536/images/system/169536.jpeg",institutionString:null,institution:{name:"Missouri State University",institutionURL:null,country:{name:"United States of America"}}},{id:"248594",title:"Ph.D.",name:"Jasneth",middleName:null,surname:"Mullings",slug:"jasneth-mullings",fullName:"Jasneth Mullings",profilePictureURL:"https://mts.intechopen.com/storage/users/248594/images/system/248594.jpeg",institutionString:"The University Of The West Indies - Mona Campus, Jamaica",institution:null},{id:"331299",title:"Prof.",name:"Pei-Shan",middleName:null,surname:"Liao",slug:"pei-shan-liao",fullName:"Pei-Shan Liao",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000032Fh2FQAS/Profile_Picture_2022-03-18T09:39:41.jpg",institutionString:"Research Center for Humanities and Social Sciences, Academia Sinica, Taiwan",institution:null}]},onlineFirstChapters:{paginationCount:2,paginationItems:[{id:"82936",title:"Soil Degradation Processes Linked to Long-Term Forest-Type Damage",doi:"10.5772/intechopen.106390",signatures:"Pavel Samec, Aleš Kučera and Gabriela Tomášová",slug:"soil-degradation-processes-linked-to-long-term-forest-type-damage",totalDownloads:3,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Forest Degradation Under Global Change",coverURL:"https://cdn.intechopen.com/books/images_new/11457.jpg",subseries:{id:"94",title:"Climate Change and Environmental Sustainability"}}},{id:"82124",title:"Assessment of Diversity, Growth Characteristics and Aboveground Biomass of Tree Species in Selected Urban Green Areas of Osogbo, Osun State",doi:"10.5772/intechopen.104982",signatures:"Omolara Aremu, Olusola O. Adetoro and Olusegun Awotoye",slug:"assessment-of-diversity-growth-characteristics-and-aboveground-biomass-of-tree-species-in-selected-u",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Forest Degradation Under Global Change",coverURL:"https://cdn.intechopen.com/books/images_new/11457.jpg",subseries:{id:"94",title:"Climate Change and Environmental Sustainability"}}}]},publishedBooks:{paginationCount:4,paginationItems:[{type:"book",id:"9869",title:"Self-Driving Vehicles and Enabling Technologies",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/9869.jpg",slug:"self-driving-vehicles-and-enabling-technologies",publishedDate:"September 22nd 2021",editedByType:"Edited by",bookSignature:"Marian Găiceanu",hash:"fd451ca2e4785ef098e04b7d695a18d9",volumeInSeries:6,fullTitle:"Self-Driving Vehicles and Enabling Technologies",editors:[{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',institutionURL:null,country:{name:"Romania"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9958",title:"Artificial Intelligence",subtitle:"Latest Advances, New Paradigms and Novel Applications",coverURL:"https://cdn.intechopen.com/books/images_new/9958.jpg",slug:"artificial-intelligence-latest-advances-new-paradigms-and-novel-applications",publishedDate:"September 1st 2021",editedByType:"Edited by",bookSignature:"Eneko Osaba, Esther Villar, Jesús L. Lobo and Ibai Laña",hash:"39648fbfdaa11385097d62b1f13aad54",volumeInSeries:5,fullTitle:"Artificial Intelligence - Latest Advances, New Paradigms and Novel Applications",editors:[{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",institutionURL:null,country:{name:"Spain"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7656",title:"Fuzzy Logic",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7656.jpg",slug:"fuzzy-logic",publishedDate:"February 5th 2020",editedByType:"Edited by",bookSignature:"Constantin Volosencu",hash:"54f092d4ffe0abf5e4172a80025019bc",volumeInSeries:3,fullTitle:"Fuzzy Logic",editors:[{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",institutionString:'"Politechnica" University Timişoara',institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7723",title:"Artificial Intelligence",subtitle:"Applications in Medicine and Biology",coverURL:"https://cdn.intechopen.com/books/images_new/7723.jpg",slug:"artificial-intelligence-applications-in-medicine-and-biology",publishedDate:"July 31st 2019",editedByType:"Edited by",bookSignature:"Marco Antonio Aceves-Fernandez",hash:"a3852659e727f95c98c740ed98146011",volumeInSeries:1,fullTitle:"Artificial Intelligence - Applications in Medicine and Biology",editors:[{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",institutionString:"Universidad Autonoma de Queretaro",institution:{name:"Autonomous University of Queretaro",institutionURL:null,country:{name:"Mexico"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},testimonialsList:[{id:"18",text:"It was great publishing with IntechOpen, the process was straightforward and I had support all along.",author:{id:"71579",name:"Berend",surname:"Olivier",institutionString:"Utrecht University",profilePictureURL:"https://mts.intechopen.com/storage/users/71579/images/system/71579.png",slug:"berend-olivier",institution:{id:"253",name:"Utrecht University",country:{id:null,name:"Netherlands"}}}},{id:"8",text:"I work with IntechOpen for a number of reasons: their professionalism, their mission in support of Open Access publishing, and the quality of their peer-reviewed publications, but also because they believe in equality.",author:{id:"202192",name:"Catrin",surname:"Rutland",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",slug:"catrin-rutland",institution:{id:"134",name:"University of Nottingham",country:{id:null,name:"United Kingdom"}}}},{id:"27",text:"The opportunity to work with a prestigious publisher allows for the possibility to collaborate with more research groups interested in animal nutrition, leading to the development of new feeding strategies and food valuation while being more sustainable with the environment, allowing more readers to learn about the subject.",author:{id:"175967",name:"Manuel",surname:"Gonzalez Ronquillo",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",slug:"manuel-gonzalez-ronquillo",institution:{id:"6221",name:"Universidad Autónoma del Estado de México",country:{id:null,name:"Mexico"}}}}]},submityourwork:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:141,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:123,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],subseriesList:[{id:"3",title:"Bacterial Infectious Diseases",scope:"