\r\n\tFurthermore, during the preparation of high-quality dairy products, several physical, chemical, enzymatic, and microbial transformations take place. We will consciously focus on this interaction of different constituents of milk under different processing conditions for the development of the products.
",isbn:"978-1-83768-093-1",printIsbn:"978-1-83768-092-4",pdfIsbn:"978-1-83768-094-8",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"420e687768b56ca7b3238d77f63f1302",bookSignature:"Prof. Salam Ibrahim",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/12173.jpg",keywords:"Protein, Fat, Lactose, Carbohydrates, Milk Processing, Milk Products, Milk Constituents, Acid Coagulated, Enzyme Treated, Heat Treated, Dairy Products, Protocols of Manufacturing",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 18th 2022",dateEndSecondStepPublish:"July 19th 2022",dateEndThirdStepPublish:"September 17th 2022",dateEndFourthStepPublish:"December 6th 2022",dateEndFifthStepPublish:"February 4th 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"a month",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:"Dr. N. Veena has been involved in different research projects such as Milkfed (Punjab), ICAR, DST, and RKVY as PI and Co-PI. She has published 17 research papers in peer-reviewed journals, edited 2 books, and authored 13 book chapters, 15 popular articles, and 7 practical manuals. She is a member of various professional bodies such as the SASNET-Fermented Foods, the Indian Dairy Association, the Association of Food Scientists and Technologists (India), and the Dairy Technology Society of India.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"107905",title:"Prof.",name:"Salam",middleName:null,surname:"Ibrahim",slug:"salam-ibrahim",fullName:"Salam Ibrahim",profilePictureURL:"https://mts.intechopen.com/storage/users/107905/images/system/107905.jfif",biography:"Dr. Salam A. Ibrahim is a food science research professor in the food and nutritional sciences program at North Carolina A&T State University. Dr. Ibrahim established a research program in dairy starter cultures, food safety, and probiotics. He has successfully conducted projects that were funded by the NIFA-USDA, DHS, other funding agencies, and the private sector. Many of his funded projects have focused on the isolation of beneficial strains and the functional characterization of related health benefits. Dr. Ibrahim became specifically interested in the characteristics of Lactobacillus bulgaricus and the effects it has on the quality of yogurt. 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From chapter submission and review to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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\n
1. Introduction
\n
Aplastic anemia (AA) is a rare disease, caused by bone marrow (BM) aggression resulting in hypo or aplastic BM with precocious fat replacement and consequently to peripheral blood pancytopenia [1, 2]. The autoimmunity process in AA occurs due to the activation of the oligoclonal cytotoxic T cells that will lead the hematopoietic cells to apoptosis. Its triggering occurs by the imbalance between CD8 +, CD4 +, T-Helper (Th), Th type 1 (Th1), Th type 2 (Th2), Th17 type (Th17), Natural Killer (NK) and T-regulatory cells (Treg). Besides, there is also an abnormal production of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) and transformed growth factor (TGF) [3, 4, 5, 6, 7].
\n
Figure 1.
Benefits of MSCs paracrine effect (immunomodulatory) on immune cells imbalance. MSCs secrete many soluble mediators, including anti-inflammatory cytokines stimulation that regulates APCs functions capable to decrease proliferation of DCs and regulate macrophage activity by polarizing proinflammatory phenotype (M1) to anti-inflammatory phenotype (M2). Therefore, they are responsible for humoral response regulation by the decrease of B cells proliferation and antibodies production. The APCs are also capable to regulate the T cell activities as well as inhibit cytotoxic T cell proliferation and upregulation and increase of Treg cells. MSCs may also promote the decrease of proinflammatory cytokines secretion. And act on the homing regulation of HSCs mechanism on stages of adhesion, expansion, and migration through chemokine and other factors secretion.
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\n
\n
\n\n
\n
AA disorders x MSC benefits
\n
\n\n\n
\n
Aberrant secretion of pro-inflammatory cytokines ↑IFN-γ ↑TNF-α ↑IL-17 ↑IL-2;
Regulate APCs functions ↓ DCs maturation and proliferation and ↓ Macrophages M1 activation ↑ Macrophages M2 activation
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\n
\n
Abnormal humoral response ↑ B cells ↑ Antibodies production
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Regulate humoral response ↓ B cells ↓ Antibodies production
\n
\n
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Irregular activity of NK cells ↑ Cytotoxicity of NK cells
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↓ Cytotoxicity of NK cells
\n
\n\n
Table 1.
Table shows disorders characterized in AA and the mechanism of action of MSCs in AA pathology.
MSC can decrease secretion of pro-inflammatory cytokines such as TGF, IFN-γ TNF-α, IL-17, regulate T cell activity, inhibit proliferation of cytotoxic T cells and stimulate Treg activity. MSC has anti-apoptotic properties, protects BM environment and recovery BM through cytoprotective effect and stimulates macrophages M2 activation and hematopoiesis improvements. MSCs may also regulate APCs functions, humoral response, and cytotoxicity of NK cells.
\n
For severe cases, immunosuppressive therapy is accepted as the first-line treatment option and the allogeneic transplantation of BM and hematopoietic stem cells (HSCs). However, 30–40% of patients with severe aplastic anemia (SAA) remain pancytopenia following the treatment. The transplant option still has a restricted number of compatibility between suitable donors. Additionally, patients aged >50 years are not eligible for transplant [8].
\n
A new viable alternative for the treatment of AA has been sought and the use of mesenchymal stem (MSCs) therapy may be a promising therapeutic candidate mainly because of their hypoimmunogenicity and the lack of rejection after transplants and immunomodulatory effects, which may promote decreasing the symptoms of the disease [9, 10]. These benefits are attributed to the paracrine effects, above all by its ability to regulate the immune system [11].
\n
Actually, is known that MSCs have wide therapeutically potential attributed by paracrine effects and the past decades have seen explosion research directed to understand better these MSCs mechanism and function [12]. One of the main and most important features of MSCs is the low expression of human leukocyte antigen (HLA) class I, with no expression of HLA class II. This feature allows the cell to be characterized as hypoimmunogenic, since it does not stimulate the patient’s immune system and can be used safely in transplants [13]. More recently, the studies showed that the main cause of AA is autoimmunity. Through the secretion of bioactive molecules, MSCs have the capacity of regulating immune responses. The mechanism of MSCs may decrease secretion of proinflammatory cytokines such as transforming growth factor (TGF), IFN-γ TNF-α, interleukin (IL)-17 and increase secretion of many soluble mediators, including anti-inflammatory cytokines stimulation that inhibit antigen-presenting cells (APCs) functions, which are capable to decrease proliferation of dendritic cells (DCs) and regulate macrophage activity by polarizing proinflammatory phenotype (M1) to anti-inflammatory phenotype (M2) [14, 15]. Therefore, the decrease of B cells proliferation and antibodies production and adjustment of T cells activities as well as inhibit the proliferation of cytotoxic T cells and stimulate Treg activity [16].
\n
MSCs therapy has gained space due to its vast therapeutic potentials such as immunomodulation mechanisms and main safety as bioproduct. Thus, this chapter will discuss the challenges of allogeneic MSCs as an alternative for an efficient therapeutic in AA immune-mediated treatment.
\n
\n
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2. Aplastic anemia: general features
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AA is a disorder characterized by BM hypocellularity, and peripheral blood pancytopenia due to a deficit of HSCs. It affects mostly children, young adults, and adults, over 60 years of age [17]. This condition can be similar to other hematologic disorders, however, in most cases, the AA is caused by reduced HSCs function, an increase in HSCs apoptosis level, consequently, the decreased of HSCs and hematopoietic progenitors and lastly, microenvironment fat replacement [18, 19].
\n
Following the patient diagnosis, AA can be considered as moderate or severe. The patients with pancytopenia may present symptoms of anemia purpura or skin hemorrhage, and in most of the cases there is an infection association, that may worsen the symptoms [20]. Three main criteria are used for the diagnostic: neutrophil count lower than 0.5 × 109 cells/L, reticulocyte count lower than 1% and platelet count lower than 20 × 109 cells/L [21]. To confirm acquired AA, the clinical case must be differentiated from other hematological diseases, as well as from the signs of malignant cell transformation or myelodysplasia [22].
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Normally the first AA etiology is uncertain and for this reason, the disorder is considered heterogeneous in origin and characterized as idiopathic [23]. AA is associated with exposures to chemical agents (pesticides and benzene), cytotoxic drugs (antineoplastics, antibiotics, non-steroidal anti-inflammatory drugs), active viral infections exposure (Epstein Barr, hepatitis virus, human immunodeficiency virus parvovirus) and radiation exposure [18, 24, 25]. However, these causes considered secondary etiologies, since the studies are directed to the primary etiology of AA to autoimmunity [26, 27]. AA pathogenesis involves an immunity dysfunction, initially provoked by the activated T cells [23], which leads to an abnormal hematopoietic microenvironment, destruction of hematopoietic stem/progenitor cell and differentiation deficiency. These findings suggest that the immune system plays an important role in the pathogenesis of AA.
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2.1 AA pathophysiology
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Currently, the studies of AA etiology are focused on the immune mechanism of hematopoietic cells destruction. Many researchers [28, 29, 30, 31] have demonstrated that the dysfunction of T cells might be a key factor in recent characterization as an autoimmune disease [28]. Most of the acquired AA is the result of an immune-mediated process as an imbalance between CD8+ and CD4+ T cells, including Th1, Th2, Treg and Th17 cells, NK, and natural killer T cells (NK T) that leads to apoptosis of BM cells triggered by cytotoxic T cells activation [6, 17].
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The abnormal immunoregulatory cell functions observed in AA can be attributable to abnormal antigen stimulation and some inappropriate T cells activation [28]. Studies demonstrated that patients with AA have a significantly increased proportion of Th1 cells, and showed a reduced fraction of natural killer T cells and regulatory T cells, together with an increased level of TNF-α, a consequent elevation of IL-6, IL-8, and IL17 productions [18]. Additionally, there is also an abnormal production of proinflammatory cytokines including IFN-γ and TGF [4, 5, 28, 32]. The new T cells subset was characterized as Th17 and currently is known that both Th17 cells and the cytokine IL-17, which is secreted by Th17 cells, also is in an association with AA pathogenesis [31]. Studies showed that AA patients who presented an increase in the frequency of Th17 cells had a positive correlation with an increase in the IFN- γ and IL-17 expression. Autoimmunity promotes inflammatory Th17 immune responses that contributed to disease pathophysiology [29].
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Otherwise, AA is attributed to inappropriate antigen stimulation and abnormal APCs activation [28], resulting in the priming of T cells specific for hematopoietic cells [33, 34]. APCs exhibit a significant increase in the expression of major histocompatibility class 2 (MHCII), increasing the recognition of CD4+ T cells. In AA, T cells are also stimulated by unknown antigens or abnormal APC activation as DCs and macrophages, which trigger a series of immune responses. Studies have shown that immunoregulatory cell dysfunction leads to a corresponding immune tolerance disorder and renders the body unable to recognize autologous hematopoietic cells [28].
\n
Although the definitive mechanism has not been identified, some genetic factors are the targets of ongoing research, such as the molecular basis of the aberrant immune response and hematopoietic cell deficiency, telomere repair gene mutations in the target cells and unregulated T cell activation pathways and cytokine genes polymorphisms [9, 26, 28]. These changes in the nucleotide sequence and gene regulation are associated with an increased immune response and suggest a genetic basis for aberrant T cells activation in BM failure [35].
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2.2 AA treatment
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The treatment depends on the severity of the disease, once for moderate cases are based on red blood cell (RBC) transfusions, on platelet transfusions to prevent bleeding, and on supportive care in association with antibiotic aiming to reestablish blood cell volume and prevent secondary infections [17]. However, the pancytopenia of many moderate cases may progress to severe [21]. For severe cases, immunosuppressive therapy is accepted as a first-line treatment option. However, 30–40% of patients with SAA remain pancytopenia following the treatment. Patients with SAA, which are refractory or have a relapse after immunosuppressive treatment, may undergo allogeneic hematopoietic stem cells transplantation (HSCT). However, about one-third of patients do not have a suitable donor for HSCT. Additionally, patients aged >50 years are not eligible for transplant [8].
\n
Furthermore, the immunosuppressive drug treatment has several side effects on patients. On the other hand, the patients often do not respond adequately to the therapies and are not suitable for life treatment (refractory patients) [24]. Therefore, immunosuppressive drugs are considered supporting AA treatment, once it does not promote the cure [20].
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2.3 Allogeneic transplantation and alternative methods for AA treatment
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Generally, patients are treated with allogeneic HSCs or whole BM transplantations, which replace since HSCs, hematopoietic precursors, until differentiated bloodstream cells and immune system cells. However, in all types of transplants, the treatment involves a combination of immunosuppressive agents or radiation therapy to prevent and to eliminate residual host BM [24]. The transplantation success varies according to risk factors, such as age and mainly histocompatibility allogeneic HLA-matched sibling donors, which are rare for the majority of patients. Despite being well established for many years, the transplanted patients can trigger late complications, such as the development of graft versus host disease (GVHD) and infections, especially in patients who have received hematopoietic grafts from HLA antigen matched donor [36, 37]. Studies show that the incidence of GVHD after unrelated donor transplantation can achieve ∼14%, and overall survival index was 57% for all 8 HLA-loci matched transplants and 39% for 1-loci mismatched transplant [38]. Thus, for BM and HSCT, the immediate challenge is the extension of stem cell therapies to all patients, regardless of age, with a histocompatible sibling [24].
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Since then a new viable alternative for the treatment of AA has been sought and the use of MSCs transplantation becomes of choice. The MSCs therapy may be a promising therapeutic candidate mainly because of their hypoimmunogenicity, the lack of rejection after transplants and immunomodulatory effects, which may promote decreasing the symptoms of the disease [39]. These benefits are attributed to MSCs paracrine effects, above all to their ability to regulate the immune system. MSCs may help for AA treatment, especially for autoimmune type [11].
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3. Mesenchymal stem cell: general features
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MSCs are multipotent progenitors, which were first isolated from an adult organism by Friedenstein and colleagues in 1968, and described years later by Caplan and colleagues [40, 41]. These cells include firstly an inherent autocrine effect, as self-renewal and differentiation potential for a variety of cell types, as main adipocytes, osteoclasts, and chondrocytes [42], depending on the surrounding microenvironment conditions [43]. Currently, such cells have shown to be isolated from many postnatal and adult tissues, such as adipose tissue, umbilical cord, placenta, dental pulp, and others [44, 45].
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Initially, the mechanism therapeutic potential of the MSCs was based only on the potential for regeneration through cellular self-renewal and its plasticity. Further studies have shown low engraft of MSCs in injured areas that questioned the hypothesis that MSCs repair tissue damage by replacing cell loss with newly differentiated cells [46, 47].
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3.1 MSC: paracrine effects
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It is known that MSCs have wide therapeutically potential attributed to paracrine effects and the past decades explosion research was directed to understand better these MSCs mechanism and function [12]. Although the therapeutic mechanisms of MSCs are not yet well characterized, it is possible to say that their paracrine effects consist in the secretion of bioactive molecules such as a variety of cytokines and growth factors as like anti-inflammatory, anti-apoptotic and angiogenic [46, 47, 48, 49, 50, 51].
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MSCs can to migrate to the lesion site through signals from specific chemokines. This process called homing consists of the steps of activating adhesion molecules, rolling to the endothelium, adhesion, and migration to the tissue that is the source of chemokine inflammation production [52, 53]. The current hypothesis is that paracrine factors secreted by MSCs promote protective microenvironment and repair by local tissue-resident progenitor populations, favoring the hypothesis of detecting favorable effects even in the absence of the cells at lesion sites [54].
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3.2 MSC: immunogenic effect and safety for transplantation
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One of the main and most important features of MSC is the low expression of HLA class I, with no expression of HLA class II. Also, MSCs do not appear to express the co-stimulatory molecules CD80 or CD86 required for effector T cell induction [55]. The absence of co-stimulatory molecules implies that any residual engagement of the T cell receptor on Th cells would result in absence of the normal immune response to a particular antigen and contribute to tolerance rather than allogeneic responses. This feature allows the cell to be characterized as hypoimmunogenic, since it does not stimulate the patient’s immune system and can be used safely in transplants [113]. As well, MSCs have properties attributed to immune functions, indicating their ability to immunomodulatory activity. Studies indicated that MSCs can regulate immune responses during chronic inflammation through the innate and adaptive immune system, regulating the recruitment and their function [56, 57].
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3.3 MSC: immunomodulatory potential
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The paracrine effects of MSCs may have great importance in the treatment of autoimmune diseases. Through the secretion of bioactive molecules, MSCs have the capacity of regulating immune responses. These cells can regulate adaptive immune responses through multiple redundant pathways, interacting with various immune cells and secreting soluble mediators such as IL-6, IL-10, prostaglandin E2 (PGE2), nitric oxide (NO), transforming growth factor-β1 (TGF-β1), and hepatocyte growth factor (HGF), indoleamine-pyrrole 2, 3-dioxygenase (IDO) [58, 59]. They can regulate APCs activity, decreasing maturation and proliferation of DCs [14]. MSC also may regulate macrophage activity by polarizing its pro-inflammatory phenotype (M1) to its anti-inflammatory phenotype (M2) [15]. Therefore, suppress T cell proliferation and activation and regulate the differentiation of Th cells and act on the humoral response by inhibiting of B cell activation and antibody production [60]. MSCs may also reduce pro-inflammatory cytokines proliferation, such TNF-α, which has an important role of the pathogenesis of autoimmune diseases and chronic inflammation (Figure 1) [14, 16, 61].
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4. MSC mechanism in AA treatment
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The first paracrine effect, showed for MSCs, was the capacity to support HSCs growth in vitro. Afterward, adipose tissue (AT) – derived MSCs also supported HSCs growth in vitro [62, 63]. Therefore, the most successful clinical application of MSCs is involved in the hematological disease.
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At BM microenvironment, MSCs niche supports hematopoietic cells and produce factors recruiting HSCs and supporting hematopoiesis [64]. This mechanism occurs through chemokine secretion of C-X-C motif chemokine ligand 12 (CXCL12), which acts on the homing regulation of HSCs, regulating the stages of adhesion, expansion and migration [65, 66]. The secretion of other factors is also important in the proliferation of HSCs mechanisms such as Flt-3 ligand (FLT3LG) [67], thrombopoietin (TPO) [68] and IL-6 [17]. That despite being a proinflammatory cytokine in general, when IL-6 is secreted in BM microenvironment, is capable to stimulate hematopoiesis [69, 70].
\n
More recently, the studies showed that the main cause of AA is autoimmunity. This process occurs in the result of an imbalance between CD8 + and CD4 + T cells, including Th1, Th2, Th17, NK, leading to the death of hematopoietic cells and their precursors [28]. Many studies have hypothesized that the onset of the immune imbalance in AA begins by stimulating APCs through an unknown antigen resulting in the T cells activation [71]. Another important mechanism of MSCs is the immunomodulation mechanism. MSCs can act directly on AA imbalance by T cells suppression, inhibiting activation and proliferation of T cells [72]. MSCs also inhibit the secretion of two important cytokines present in the pathology of AA, the INF-γ and TNF-α and stimulate the proliferation of Treg, promoting the production of the anti-inflammatory cytokine IL-10 Table 1 [73, 74]. In addition, some studies also show that MSCs also acts through its anti-apoptotic effects [75].
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5. Biodistribution and engraftment of allogeneic MSC in BM
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In the last years, several studies have been exploring intravenous administrations (IV) due to being safe and do not present morbidity risk for patients. However, still lack the data about the biodistribution mechanism of MSCs and about how these cells engraftment on the target organ, which is essential for the success of clinical studies. It is known that the biodistribution is influenced in vivo and in vitro conditions. Stromal cell-derived factor 1 (SDF-1) (also known as CXCL12) is upregulated at sites of injury and acts as a chemoattractant to recruit circulating or residing MSCs expressing its cognate receptor CXC chemokine receptor 4 (CXCR4). It has been demonstrated that the CXCR4-SDF-1 axis is critical for BM homing [76]. Diverse studies demonstrate that some in vitro conditions may influence the expression of adhesion molecules [77, 78]. For instance, long expansion periods [79] and cells culturing at high density may reduce CXCR4 cell expression; the cells cultured at higher confluence secrete more metalloproteinase inhibitor 3, which decreases migration of MSCs when compared to those cultured at the low confluence [80]. Hypoxia condition may increase CXCR4 expression; on the other hand, hypoxia may decrease matrix metalloproteinase-2 secretion and an increase in membrane-type 1 matrix metalloproteinase [81].
\n
In vivo engraftment is influenced by interactions of MSCs with different types of immune cells that depend on their ability to respond to signals from the immune system. On the other hands, the MSCs biodistribution and homing depend on the host niche. Interesting the MSCs migration and homing to target tissue can be influenced positively by irradiation. It has been demonstrated an increased absolute number of human MSCs in the brain, heart, bone marrow, and muscles after total body irradiation and MSCs IV administrations in mice, when compared to the untreated control [82].
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Some animal studies evidence that MSCs can engraftment in BM after systemic administration [83]. Studies in patients showed MSCs engraftment into BM 30 days after the second MSCs IV administration. Although, after MSCs infusion was observed no recovery of hematopoietic tissue, interstitial hemorrhage, edema, and all adipocytic necrosis disappeared in BM [84]. Other studies indicate the engraftment due to myeloid and plated recovery after HSCs and MSCs transplantation [85, 86].
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6. MSC use in clinical studies
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6.1 Clinical potential and market of MSC in hematopoietic disorders
\n
MSCs have been implicated in immunomodulatory therapy, in particular, in GVHD treatment and as an adjunct to hematopoietic stem cell transplantation (HSCT) to help enhance engraftment [87, 88]. The first major clinical trial of MSCs (Prochymal) was for the treatment of steroid-refractory of GVHD (NCT00366145) [89, 90]. The primary endpoint of the study was complete remission at day 28 after allogeneic BM-MSCs infusion but was not significantly increased compared to placebo [89, 91]. In 2012, MSCs have bens conditional approval to treat children GVHD in Canada, based on subset analysis that suggested children with GVHD were responsive to MSCs [89, 92, 93]. Many new studies have been developed in recent years; however, a few of them have attempted to look at biological correlates of response to therapy. Isolated studies reported serum biomarkers of GVHD severity including IL-2, tumor necrosis factor receptor 1 (TNFR1), regenerating islet-derived protein 3 alpha (Reg3a), and levels of inflammatory cytokines, which not clearly correlate with the response in humans. More studies are needed to obtain correlative research data [94, 95]. This outcome results in the first Food and Drug Administration (FDA) approved MSCs product in the United States [96, 97].
\n
\n
\n
6.2 Clinical studies with MSC in combination to HSCT transplantation for treat AA
\n
Cotransplantation of HSCs with (umbilical cord) UC-MSCs has been performed to study whether the last will be able to support hematopoiesis, enhance the engraftment of HSCs, and reduce the incidence of GVHD following HSCT [98, 99, 100]. These studies include adult and children in AA patients [101, 102]. Stem cells application was mainly intravenous. In some of the studies multiple (five) infusions were used. All clinical protocols have been developed in the presence of traditional immunosuppressive protocol to prevent GVHD manifestation [98, 99, 100, 101, 102].
\n
One pioneer study, where the conditioning of patients was myeloablative or reduced, followed BM-MSCs treatment together with allogeneic HSCT. This study showed that co-transplantation of MSCs resulted in fast engraftment of absolute neutrophil count and platelets and 100% donor chimerism [87]. In turn, Yamei and co-workers (2014) demonstrate prolonged survival (follow up of 78 months) in 80.9% patients after cotransplantation of the culture-expanded third party donor-derived UC-MSCs in 21 young people with SAA undergoing haplo-HSCT [103]. Even so, the patients did not show infusion toxicity. This study showed that MSCs support in vivonormal hematopoiesis and display potent immunosuppressive effects. The other metacentric study shows that cotransplantation of BM-MSCs and haplo-HSCT could reduce the risk of graft failure and severe GVHD in SAA [104]. Similar data were obtained in a study that used cotransplantation of haploidentical HSCs and BM-MSCs into children with SAA without an HLA-identical sibling donor. It was shown that such cotransplantation seems to be safe and may improve survival rates and reduce the risk of graft failure [105]. Another multicenter study, which explored cotransplantation of BM-MSCs with allo-HSCT, reported that such treatment could ameliorate clinical outcomes of a GVHD, viremia, and survival in allo-HSCT for AA patients [106].
\n
\n
\n
6.3 Clinical studies with MSC for treat AA
\n
Nowadays there a few clinical studies using only MSCs single to treat AA. All studies used MSCs isolated from BM s and adult patients with severe or non-severe AA and refractory. The via of MSCs administration used was IV and the number of administrations was 2 until 5 depending on study in combination with conventional immunosuppressive therapy.
\n
The study development by Pang et al. showed, six of 18 patients (33.3%) achieved a complete response or a partial response to MSCs treatment [107]. In six patients, two achieved a complete response including recovery of three hematopoietic cell lines after MSCs therapy. Similar results was achieved by Cle et al. 2015 using MSCs being 22% of all patients (18 patients) presents hematologic response at 6 months after MSCs transplantation [108]. One clinical trial phase II conducted in China evaluated the MSC overall response rate and safety using a significant number of refractory AA younger patients (n = 72). The study performed full quality control of BM-MSCs production, which includes counts, viability, morphology, endotoxin, aseptic culture, immunophenotype. It was the first clinical study that showed significant results in BM functional recovery. The rate response of patients was 28.4% being that 6.8% complete response and 21.6% partial response after MSCs transplantation. Among patients with hematologic response, ten patients had normalization of cellularity BM followed for more than 1 year MSCs transplantation. Seven patients got adverse events such as fever and headaches. No other adverse events were observed in the study. At the follow-up endpoint, nine patients died. One patient with RAEB-II died of disease progression, two patients died of intracranial hemorrhages, and six patients died of serious infection [107]. In other two studies were reported adverse events such as, fever, hypoxemia, mild dyspnea and diarrhea during MSCs administration or some hours after MSCs injection, this phenomenon occurs in 2 of 16 patients [107] and 7 of the 18 patients [108]. None major adverse effects were reported in all studies during months of follow-up of each respective study. Fuillard et al., 2003 reported one death due to fungal infection and Cle et al. 2015 four patients died in consequence result of heart failure and bacterial or invasive fungal infections and none of the deaths in both studies were directly attributable to MSCs infusions [84, 108].
\n
These preliminary studies support the concept that MSCs replacement can improve BM stroma and may alleviate symptoms severe and non-severe AA patients. However, larger studies with a significant number of patients are needed to evaluate the utility of MSCs further.
\n
\n
\n
\n
7. Conclusion and future perspectives
\n
The progress in dissecting the underlying and complex pathophysiology of AA has been gain space over the past years in the hematology research community [26]. In addition to that, the need for an optimal alternative of a targeted treatment for this disorder. It is too soon to place the conventional AA treatment methods, but MSCs have gained space for demonstrating positive results in several AA clinical studies and other hematological diseases. The hypoimmunogenicity advantages, ensuring the absence of rejection in patients due to no expression of MHC class II, prevention and treatment of GVHD traditional transplants, and mainly immunomodulatory action presented [109]. Essential in the environment imbalance provoked by own immune system in people committed by the AA disorder. The MSCs are able in a modulating way to relieve the BM self-attack [110].
\n
Contemporary, personalized therapies are famous in the whole scientific world. The MSCs may fit into this class due to their paracrine effects. These cells can assist in diverse situations such as: migration, injury recovery, stimulates cells renewal, death cell prevention, anti-inflammatory and modulation of the immune system to control the autoimmune environment [111]. Thus, MSCs have the heterogeneous capacity in varied therapies field. And the patient may have alternative use according to their needs.
\n
In that event, the current way is providing the MSCs safety and acceptance by regulatory agencies as new biological product [112], which has already been proven to be more efficient than synthetic industries products [113]. And finally, implement the MSCs as ideal allogeneic transplant model, even for adequacy periods used as support for other established therapies.
\n
\n
Acknowledgments
\n
Thanks to everyone on the Cellavita team who helped us so much. Special thanks to the company Cellavita Ltda., for financial and professional supporting. And to Butantan Institute, to providing us space and the research opportunity.
\n
Conflict of interest
The authors declare no conflict of interest.
\n',keywords:"allogeneic transplant, mesenchymal stem cell, immune-mediated aplastic anemia, paracrine effects, immunomodulation",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/68976.pdf",chapterXML:"https://mts.intechopen.com/source/xml/68976.xml",downloadPdfUrl:"/chapter/pdf-download/68976",previewPdfUrl:"/chapter/pdf-preview/68976",totalDownloads:841,totalViews:0,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:0,introChapter:null,impactScore:0,impactScorePercentile:35,impactScoreQuartile:2,hasAltmetrics:0,dateSubmitted:"May 7th 2019",dateReviewed:"August 8th 2019",datePrePublished:"September 26th 2019",datePublished:"February 17th 2021",dateFinished:"September 9th 2019",readingETA:"0",abstract:"Acquired aplastic anemia (AA) is characterized by partial or total bone marrow (BM) destruction resulting in pancytopenia. Most of the acquired AA is the result of autoimmune condition the imbalance between T-regulatory cells (Treg), abnormal cytokines production and cytotoxic T cells activation, leading to the hematopoietic stem cells (HSCs) death. The first-line treatment is given by HSC transplant, but some patients did not respond to the treatment. Therefore, new technologies need to treat AA nonresponder patients. Studies are in progress to test the efficacy of stem cell-based therapeutic as mesenchymal stem cells (MSCs), which confer low immunogenicity and are reliable allogeneic transplants in refractory severe AA cases. Furthermore, MSCs comprise the BM stromal niche and have an important role in supporting hematopoiesis by secreting regulatory cytokines, providing stimulus to natural BM microenvironment. In addition, MSCs have immunomodulatory property and are candidates for efficient supporting AA therapy.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/68976",risUrl:"/chapter/ris/68976",book:{id:"9027",slug:"human-blood-group-systems-and-haemoglobinopathies"},signatures:"Vivian Gonzaga, Bruna Policiquio, Cristiane Wenceslau and Irina Kerkis",authors:[{id:"156995",title:"Dr.",name:"Cristiane",middleName:null,surname:"Wenceslau",fullName:"Cristiane Wenceslau",slug:"cristiane-wenceslau",email:"wenceslauvet@yahoo.com.br",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"301415",title:"Prof.",name:"Irina",middleName:null,surname:"Kerkis",fullName:"Irina Kerkis",slug:"irina-kerkis",email:"irina.kerkis@butantan.gov.br",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Instituto Butantan",institutionURL:null,country:{name:"Brazil"}}},{id:"304360",title:"MSc.",name:"Vivian",middleName:null,surname:"Gonzaga",fullName:"Vivian Gonzaga",slug:"vivian-gonzaga",email:"vivia_gonzaga@hotmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"304363",title:"Ms.",name:"Bruna",middleName:null,surname:"Policiquio",fullName:"Bruna Policiquio",slug:"bruna-policiquio",email:"bruna.policiquio@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Instituto Butantan",institutionURL:null,country:{name:"Brazil"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Aplastic anemia: general features",level:"1"},{id:"sec_2_2",title:"2.1 AA pathophysiology",level:"2"},{id:"sec_3_2",title:"2.2 AA treatment",level:"2"},{id:"sec_4_2",title:"2.3 Allogeneic transplantation and alternative methods for AA treatment",level:"2"},{id:"sec_6",title:"3. Mesenchymal stem cell: general features",level:"1"},{id:"sec_6_2",title:"3.1 MSC: paracrine effects",level:"2"},{id:"sec_7_2",title:"3.2 MSC: immunogenic effect and safety for transplantation",level:"2"},{id:"sec_8_2",title:"3.3 MSC: immunomodulatory potential",level:"2"},{id:"sec_10",title:"4. MSC mechanism in AA treatment",level:"1"},{id:"sec_11",title:"5. Biodistribution and engraftment of allogeneic MSC in BM",level:"1"},{id:"sec_12",title:"6. MSC use in clinical studies",level:"1"},{id:"sec_12_2",title:"6.1 Clinical potential and market of MSC in hematopoietic disorders",level:"2"},{id:"sec_13_2",title:"6.2 Clinical studies with MSC in combination to HSCT transplantation for treat AA",level:"2"},{id:"sec_14_2",title:"6.3 Clinical studies with MSC for treat AA",level:"2"},{id:"sec_16",title:"7. Conclusion and future perspectives",level:"1"},{id:"sec_17",title:"Acknowledgments",level:"1"},{id:"sec_20",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'\nMedinger M, Drexler B, Lengerke C, Passweg J. Pathogenesis of acquired aplastic anemia and the role of the bone marrow microenvironment. Frontiers in Oncology. 2018;8:587. DOI: 10.3389/fonc.2018.00587\n'},{id:"B2",body:'\nMarsh JCW, Ball SE, Cavenagh J, Darbyshire P, Dokal I, Gordon-Smith EC, et al. Guidelines for the diagnosis and management of aplastic anaemia. British Journal of Haematology. 2009;147:43-70. 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DOI: 10.1089/scd.2009.0345\n'},{id:"B59",body:'\nGao F, Chiu SM, Motan DAL, Zhang Z, Chen L, Ji HL, et al. Mesenchymal stem cells and immunomodulation: Current status and future prospects. Cell Death & Disease. 2016;7:e2062. DOI: 10.1038/cddis.2015.327\n'},{id:"B60",body:'\nHerrero C, Pérez-Simón JA. Immunomodulatory effect of mesenchymal stem cells. Brazilian Journal of Medical and Biological Research. 2010;43:425-430. DOI: 10.1590/S0100-879X2010007500033\n'},{id:"B61",body:'\nCastro-Manrreza ME, Montesinos JJ. Immunoregulation by mesenchymal stem cells: Biological aspects and clinical applications. Journal of Immunology Research. 2015;2015. DOI: 10.1155/2015/394917\n'},{id:"B62",body:'\nNakao N, Nakayama T, Yahata T, Muguruma Y, Saito S, Miyata Y, et al. Adipose tissue-derived mesenchymal stem cells facilitate hematopoiesis in vitro and in vivo: Advantages over bone marrow-derived mesenchymal stem cells. The American Journal of Pathology. 2010;177(2):547-554. DOI: 10.2353/ajpath.2010.091042\n'},{id:"B63",body:'\nDexter TM. Stromal cell associated Haemopoiesis. Journal of Cellular Physiology. Supplement. 1982;1:87-94\n'},{id:"B64",body:'\nHamzic E, Whiting K, Gordon Smith E, Pettengell R. Characterization of bone marrow mesenchymal stromal cells in aplastic anaemia. British Journal of Haematology. 2015;169(6):804-813. DOI: 10.1111/bjh.13364\n'},{id:"B65",body:'\nSugiyama T, Kohara H, Noda M, Nagasawa T. Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity. 2006;25(6):977-988. DOI: 10.1016/j.immuni.2006.10.016\n'},{id:"B66",body:'\nAsri A, Sabour J, Atashi A, Soleimani M. Homing in hematopoietic stem cells: Focus on regulatory role of CXCR7 on SDF1A/CXCR4 axis. EXCLI Journal. 2016;15:134-143. DOI: 10.17179/excli2014-585\n'},{id:"B67",body:'\nOubari F, Amirizade N, Mohammadpour H, Nakhlestani M, Zarif MN. The important role of FLT3-L in ex vivo expansion of hematopoietic stem cells following co-culture with mesenchymal stem cells. Cell Journal. 2015;17(2):201-210. DOI: 10.22074/cellj.2016.3715\n'},{id:"B68",body:'\nAnthony BA, Link DC. Regulation of hematopoietic stem cells by bone marrow stromal cells. Trends in Immunology. 2014;35:32-37. DOI: 10.1016/j.it.2013.10.002\n'},{id:"B69",body:'\nTvedt THA, Ersvaer E, Tveita AA, Bruserud Ø. Interleukin-6 in allogeneic stem cell transplantation: Its possible importance for immunoregulation and as a therapeutic target. Frontiers in Immunology. 2017;8:667. DOI: 10.3389/fimmu.2017.00667\n'},{id:"B70",body:'\nPatchen ML, Macvittie TJ, Williams JL, Schwartz GN, Souza LM. Administration of Interleukin-6 stimulates multilineage Hematopoiesis and accelerates recovery from radiation-induced hematopoietic depression. Blood. 1991;77(3):472-480\n'},{id:"B71",body:'\nYoung NS. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood. 2006;108(8):2509-2519. DOI: 10.1182/blood-2006-03-010777\n'},{id:"B72",body:'\nBacigalupo A, Valle M, Podestà M, Pitto A, Zocchi E, De Flora A, et al. T-cell suppression mediated by mesenchymal stem cells is deficient in patients with severe aplastic anemia. Experimental Hematology. 2005;33(7):819-827. DOI: 10.1016/j.exphem.2005.05.006\n'},{id:"B73",body:'\nLi J, Lu S, Yang S, Xing W, Feng J, Li W, et al. Impaired immunomodulatory ability of bone marrow mesenchymal stem cells on CD4 + T cells in aplastic anemia. Results in Immunology. 2012;2:142-147. DOI: 10.1016/j.rinim.2012.07.002\n'},{id:"B74",body:'\nKyurkchiev D. Secretion of immunoregulatory cytokines by mesenchymal stem cells. World Journal of Stem Cells. 2014;6(5):552. DOI: 10.4252/wjsc.v6.i5.552\n'},{id:"B75",body:'\nQiao SK, Ren HY, Shi YJ, Liu W. Allogeneic compact bone-derived mesenchymal stem cell transplantation increases survival of mice exposed to lethal total body irradiation: A potential immunological mechanism. Chinese Medical Journal. 2014;127(3):475-482. DOI: 10.3760/cma.j.issn.0366-6999.20132001\n'},{id:"B76",body:'\nMoll NM, Ransohoff RM. CXCL12 and CXCR4 in bone marrow physiology. Expert Review of Hematology. 2010;3:315-322. DOI: 10.1586/ehm.10.16\n'},{id:"B77",body:'\nDar A, Goichberg P, Shinder V, Kalinkovich A, Kollet O, Netzer N, et al. Chemokine receptor CXCR4-dependent internalization and resecretion of functional chemokine SDF-1 by bone marrow endothelial and stromal cells. Nature Immunology. 2005;6(10):1038-1046. DOI: 10.1038/ni1251\n'},{id:"B78",body:'\nYang JX, Zhang N, Wang HW, Gao P, Yang QP, Wen QP. CXCR4 receptor overexpression in mesenchymal stem cells facilitates treatment of acute lung injury in rats. The Journal of Biological Chemistry. 2015;290(4):1994-2006. DOI: 10.1074/jbc.M114.605063\n'},{id:"B79",body:'\nHonczarenko M, Le Y, Swierkowski M, Ghiran I, Glodek AM, Silberstein LE. Human bone marrow stromal cells express a distinct set of biologically functional chemokine receptors. Stem Cells. 2006;24(4):1030-1041. DOI: 10.1634/stemcells.2005-0319\n'},{id:"B80",body:'\nDe Becker A, Van Hummelen P, Bakkus M, Vande BI, De Wever J, De Waele M, et al. Migration of culture-expanded human mesenchymal stem cells through bone marrow endothelium is regulated by matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-3. Haematologica. 2007;92(4):440-449. DOI: 10.3324/haematol.10475\n'},{id:"B81",body:'\nAnnabi B, Lee Y-T, Turcotte S, Naud E, Desrosiers RR, Champagne M, et al. Hypoxia promotes murine bone-marrow-derived stromal cell migration and tube formation. Stem Cells. 2003;21(3):337-347. DOI: 10.1634/stemcells.21-3-337\n'},{id:"B82",body:'\nFrançois M, Romieu-Mourez R, Li M, Galipeau J. Human MSC suppression correlates with cytokine induction of indoleamine 2,3-dioxygenase and bystander M2 macrophage differentiation. Molecular Therapy. 2012;20(1):187-195. DOI: 10.1038/mt.2011.189\n'},{id:"B83",body:'\nGan J, En G FM, O U XZ, I CL, E YH, Zen XG, et al. Cross mark. Cytotherapy 2015;17:403-417. DOI: 10.1016/j.jcyt.2014.ll.011\n'},{id:"B84",body:'\nFouillard L, Bensidhoum M, Bories D, Bonte H, Lopez M, Moseley AM, et al. Engraftment of allogeneic mesenchymal stem cells in the bone marrow of a patient with severe idiopathic aplastic anemia improves stroma. Leukemia. 2003;17:474-476. DOI: 10.1038/sj.leu.2402786\n'},{id:"B85",body:'\nHematti P, Kim J, Battiwalla M. Mesenchymal stem cells in hematopoietic stem cell transplantation. In: Stem Cells and Human Diseases. Springer Netherlands; 2014. pp. 101-115. DOI: 10.1007/978-94-007-2801-1_5\n'},{id:"B86",body:'\nLiu FD, Tam K, Pishesha N, Poon Z, Van Vliet KJ. Improving hematopoietic recovery through modeling and modulation of the mesenchymal stromal cell secretome. Stem Cell Research & Therapy. 2018;9(1):268. DOI: 10.1186/s13287-018-0982-2\n'},{id:"B87",body:'\nLe Blanc K, Samuelsson H, Gustafsson B, Remberger M, Sundberg B, Arvidson J, et al. Transplantation of mesenchymal stem cells to enhance engraftment of hematopoietic stem cells. Leukemia. 2007;21(8):1733-1738. DOI: 10.1038/sj.leu.2404777\n'},{id:"B88",body:'\nFang B, Li N, Song Y, Li J, Zhao RC, Ma Y. Cotransplantation of haploidentical mesenchymal stem cells to enhance engraftment of hematopoietic stem cells and to reduce the risk of graft failure in two children with severe aplastic anemia. Pediatric Transplantation. 2009;13(4):499-502. DOI: 10.1111/j.1399-3046.2008.01002.x\n'},{id:"B89",body:'\nKurtzberg J, Prockop S, Teira P, Bittencourt H, Lewis V, Chan KW, et al. Allogeneic human mesenchymal stem cell therapy (Remestemcel-L, Prochymal) as a rescue agent for severe refractory acute graft-versus-host disease in pediatric patients. Biology of Blood and Marrow Transplantation. 2014;20(2):229-235. DOI: 10.1016/j.bbmt.2013.11.001\n'},{id:"B90",body:'\nČesen Mazič M, Girandon L, Kneževič M, Avčin SL, Jazbec J. Treatment of severe steroid-refractory acute-graft-vs.-host disease with mesenchymal stem cells–single center experience. Frontiers in Bioengineering and Biotechnology. 2018;6. DOI: 10.3389/fbioe.2018.00093\n'},{id:"B91",body:'\nBaron F, Storb R. Mesenchymal stromal cells: A new tool against graft-versus-host disease? Biology of Blood and Marrow Transplantation. 2012;18:822-840. DOI: 10.1016/j.bbmt.2011.09.003\n'},{id:"B92",body:'\nVan Pham P. Mesenchymal stem cells in clinical applications. In: Stem Cell Processing. Cham: Springer; 2016. pp. 37-69. DOI: 10.1007/978-3-319-40073-0_2\n'},{id:"B93",body:'\nKeto J, Kaartinen T, Salmenniemi U, Castrén J, Partanen J, Hänninen A, et al. Immunomonitoring of MSC-treated GvHD patients reveals only moderate potential for response prediction but indicates treatment safety. Molecular Therapy. Methods & Clinical Development. 2018;9:109-118. DOI: 10.1016/j.omtm.2018.02.001\n'},{id:"B94",body:'\nGalleu A, Milojkovic D, Deplano S, Szydlo R, Loaiza S, Wynn R, et al. Mesenchymal stromal cells for acute graft-versus-host disease: Response at 1 week predicts probability of survival. British Journal of Haematology. 2019;185(1):89-92. DOI: 10.1111/bjh.15749\n'},{id:"B95",body:'\nElgaz S, Kuçi Z, Kuçi S, Bönig H, Bader P. Clinical use of mesenchymal stromal cells in the treatment of acute graft-versus-host disease. Transfusion Medicine and Hemotherapy. 2019;46:27-34. DOI: 10.1159/000496809\n'},{id:"B96",body:'\nGalipeau J, Sensébé L. Mesenchymal stromal cells: Clinical challenges and therapeutic opportunities. Cell Stem Cell. 2018;22:824-833. DOI: 10.1016/j.stem.2018.05.004\n'},{id:"B97",body:'\nSeng A, Dunavin N. Mesenchymal stromal cell infusions for acute graft-versus-host disease: Rationale, data, and unanswered questions. Advances in Cell and Gene Therapy. 2018;1(2):e14. DOI: 10.1002/acg2.14\n'},{id:"B98",body:'\nTipnis S, Viswanathan C. Umbilical cord matrix derived mesenchymal stem cells can change the cord blood transplant scenario. Int J Stem Cells. 2010;3(2):103-118. DOI: 10.15283/ijsc.2010.3.2.103\n'},{id:"B99",body:'\nRizvanov AA, Persson J, Şahin F, Bellusci S, Oliveira PJ. Hematopoietic and mesenchymal stem cells in biomedical and clinical applications. Stem Cells International. 2016;2016. DOI: 10.1155/2016/3157365\n'},{id:"B100",body:'\nFernández-García M, Yañez RM, Sánchez-Domínguez R, Hernando-Rodriguez M, Peces-Barba M, Herrera G, et al. Mesenchymal stromal cells enhance the engraftment of hematopoietic stem cells in an autologous mouse transplantation model. Stem Cell Research & Therapy. 2015;6(1):165. DOI: 10.1186/s13287-015-0155-5\n'},{id:"B101",body:'\nLi H, Wang L, Pang Y, Jiang Z, Liu Z, Xiao H, et al. In patients with chronic aplastic anemia, bone marrow-derived MSCs regulate the Treg/Th17 balance by influencing the notch/RBP-J/FOXP3/RORγt pathway. Scientific Reports. 2017;7:42488. DOI: 10.1038/srep42488\n'},{id:"B102",body:'\nJaganathan BG, Tisato V, Vulliamy T, Dokal I, Marsh J, Dazzi F, et al. Effects of MSC co-injection on the reconstitution of aplastic anemia patient following hematopoietic stem cell transplantation. Leukemia. 2010;24:1791-1795. DOI: 10.1038/leu.2010.164\n'},{id:"B103",body:'\nYamei W, Rongmu L, Yongbin C, Yingjian S, Xiaohong L, Xiaomei Z, et al. Improved outcome of haploidentical transplantation in severe aplastic anemia using reduced-intensity fludarabine-based conditioning. Oncotarget. 2017;8(48):83817. DOI: 10.18632/oncotarget.19745\n'},{id:"B104",body:'\nLiu Z, Zhang Y, Xiao H, Yao Z, Zhang H, Liu Q , et al. Cotransplantation of bone marrow-derived mesenchymal stem cells in haploidentical hematopoietic stem cell transplantation in patients with severe aplastic anemia: An interim summary for a multicenter phase II trial results. Bone Marrow Transplantation. 2017;52(5):704-710. DOI: 10.1038/bmt.2016.347\n'},{id:"B105",body:'\nWang ZK, Yu HJ, Cao FL, Liu ZH, Liu ZY, Feng WJ, et al. Donor-derived marrow mesenchymal stromal cell co-transplantation following a haploidentical hematopoietic stem cell transplantation trail to treat severe aplastic anemia in children. Annals of Hematology. 2019;98(2):473-479. DOI: 10.1007/s00277-018-3523-2\n'},{id:"B106",body:'\nChen M, Zheng Z, He G, Lin S, Zhang D, Hu H, et al. Co-transplantation of mesenchymal stem cells can ameliorates acute Gvhd and viremia after allogeneic hematopoietic stem cell transplantation for severe aplastic Anemia: A multi-Center retrospective study of 119 patients. Blood. 2018;132(1):4653-4653. DOI: 10.1182/blood-2018-99-118758\n'},{id:"B107",body:'\nPang Y, Xiao HW, Zhang H, Liu ZH, Li L, Gao Y, et al. Allogeneic bone marrow-derived mesenchymal stromal cells expanded In vitro for treatment of aplastic Anemia: A Multicenter phase II trial. Stem Cells Translational Medicine. 2017;6(7):1569-1575. DOI: 10.1002/sctm.16-0227\n'},{id:"B108",body:'\nClé DV, Santana-Lemos B, Tellechea MF, Prata KL, Orellana MD, Covas DT, et al. Intravenous infusion of allogeneic mesenchymal stromal cells in refractory or relapsed aplastic anemia. Cytotherapy. 2015;17(12):1696-1705. DOI: 10.1016/j.jcyt.2015.09.006\n'},{id:"B109",body:'\nKim HJ, Park J-S. Usage of human mesenchymal stem cells in cell-based therapy: Advantages and disadvantages. Development & Reproduction. 2017;21(1):1-10. DOI: 10.12717/dr.2017.21.1.001\n'},{id:"B110",body:'\nFigueroa FE, Carrión F, Villanueva S, Khoury M. Mesenchymal stem cell treatment for autoimmune diseases: A critical review. Biological Research. 2012;45(3):269-277. DOI: 10.4067/S0716-97602012000300008\n'},{id:"B111",body:'\nParekkadan B, Milwid JM. Mesenchymal stem cells as therapeutics. Annual Review of Biomedical Engineering. 2010;12(1):87-117. DOI: 10.1146/annurev-bioeng-070909-105309\n'},{id:"B112",body:'\nFagioli F, Ferrero I. Mesenchymal stem cell manufacturing for clinical use. In: Progress in Stem Cell Transplantation. Rijeka: InTechOpen; 2015. DOI: 10.5772/61370\n'},{id:"B113",body:'\nErickson B, Nelson WP. Perspective on opportunities in industrial biotechnology in renewable chemicals. Biotechnology Journal. 2012;7:176-185. DOI: 10.1002/biot.201100069\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Vivian Gonzaga",address:"vivia_gonzaga@hotmail.com",affiliation:'
Laboratory of Genetics, Butantan Institute, Brazil
Laboratory of Genetics, Butantan Institute, Brazil
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1. Introduction
The first sheep were brought to the Magallanes region from Chiloe in 1845 as a food source for the region’s new human settlements. The Magallanes governor encouraged the development of a larger sheep industry, which began in January 1877 with the arrival of the first Cheviot sheep from the Falkland Islands (Malvinas). Progress in Magallanes throughout the last 145 years has transformed the region into the most important sheep farming area of Chile via the development of both, meat and wool production. In the last 20 years, improvements have been realized through a strategic use of management techniques (strategic feeding, grazing, soil fertility, water supply, crossbreeding and brush control) and new technologies (plow machinery, direct drilling, artificial insemination, embryo transfer, dietary supplement formulation, satellite imagery, silage baling, and electric fence) that have enhanced both, process efficiency and product quality, forward to sustainability management.
To understand the different aspects of sheep farming and its development within the socioeconomic and environmental context of the Magallanes region, this chapter covers topics including location, climatic conditions and main characteristics of the livestock use area, common grazing management systems, locally-adapted fodder crops, artificial insemination, the main breeds (Corriedale, Merino mainly and meat crossbreed), breeding, lamb meat quality under different grazing regimes, wool management, lactation curve and cheese production, animal welfare, sheep-wildlife interactions, and rural tourism.
2. Geographical area and weather
The Magallanes region corresponds to an extensive territory located in the extreme south of Chile and the South American continent, encompassing the meridional section of Patagonia and the occidental part of the Isla Grande de Tierra del Fuego, and the numerous archipelagos that make up a strip adjacent to both parts, ending in the south with the Cape Horn archipelago. The region extends from 48° 40′ to 56° 30′ south latitude (the greatest latitudinal amplitude in Chile), covering an area of 132,033.5 km2 (Figure 1A) [1]. The region is characterized by a marked physical contrast, generating different geological, orographic and climatic zones, which determine high amplitude in terms of vegetation types [3]. Likewise, there is a pronounced gradient of precipitation from west to east, going from more than 5.000 to less than 200 mm per year respectively [4, 5]. These characteristics make it evident that, in Magallanes, the territory of the eastern section is the most suitable for human life, and that is where the cattle activity has been established since 1870 [1, 6].
Figure 1.
Cartographies of the area of livestock use in the Magellan region. A: General location. B: Livestock use according to administrative division. C: Elevation ranges. Source: Own elaboration from ASTER GDEM digital elevation model. D: isohyets (mm·year−1) and isotherms (annual mean ° C) (prepared by author based in Ref. [2]).
The livestock use area is located mainly in the eastern section of the Magallanes region, extending between 50° 36′ and 55° 19′ south latitude and 67° 2 ‘and 73° 47’ west longitude, covering a surface area of 35,962.6 km2 distributed mainly in the provinces of Magallanes, Tierra del Fuego and Ultima Esperanza (15,577.9, 13,502.2 and 6,559.9 km2 respectively). With less representativeness and in the southernmost distribution lies the livestock territory of the Chilean Antarctic province with 322.5 km2(Figure 1B) [7]. The livestock use area can be divided into three provinces from north to south (the area corresponding to the Chilean Antarctic province is not considered in this analysis). The first section located in the Ultima Esperanza province presents spatial and topographic patterns different from the other sections (Magallanes and Tierra del Fuego), corresponding mainly to a transition strip between mountain ranges and the eastern plains, characterized by plateau sectors crossed by mountain chains with heights that rarely exceed 1000 masl (Figure 1B). The Magallanes and Tierra del Fuego sections present similar characteristics, beginning with a western sub-Andean transition strip that gives way to extensive eastern plains, corresponding to mainly flat territories, with low elevations and moderate undulations (Figure 1C) [3].
According to [8], from a climatic point of view, based on Koppen classification, this area can be defined as a trans-Andean climate with steppe degeneration in its western fringe and a cold steppe climate in the eastern plains sector. In the former, we can find annual average temperatures ranging from 2.6 to 6.6° C, while in the cold steppe climate the annual average temperatures can range between 4 and 7.4°C (Figure 1D) [2, 8]. On the other hand, the area of interest is located in the sotavento zone (east) of the Andean Patagonian mountain range, which despite presenting spatial discontinuities in its southern distribution, is the main geographical feature of the region and forms an orographic barrier that generates local climatic changes [5, 9]. This is how rainfall in the livestock use area can drop from approximately 600 mm to less than 200 mm per year in the direction of the Atlantic coast in the sections of Magallanes and Tierra del Fuego, while in Ultima Esperanza the rainfall ranges from 1,000 mm to 300 mm in the same direction W-E (Figure 1D) [2].
The marked variation in rainfall in the area of livestock use is reflected in the present vegetation, which could be categorized into three ecoregions: the Patagonian steppe, the deciduous Magellan forest and evergreen forest, but the latter have a small participation. The dominates the sub-Andean region, is present in the three provinces of the area of livestock use, characterized by associations of Nothofagus pumilio (lenga) and also including forests of Nothofagus antarctica (ñirre) and associations with Nothofagus betuloides (coihue de Magallanes) in the most humid sectors [3]. It is worth mentioning that in this ecoregion and specifically in the area of livestock use, there are extensive areas of forests that were formerly burned with the purpose of enabling land for livestock [10] and that today are known as naturalized grasslands. Dominating the area of the eastern plains, we find the Patagonian steppe, defined as a hard grass community without the presence of trees [8]. The characteristic specie of this ecoregion in Magallanes is the tussock coiron (Festuca gracillima), which may be present to different degrees of dominance or even absent in some cases. In this ecoregion, three large types of communities can be distinguished: a) natural grasslands, made up of coiron grasslands, vegas (mesic grasslands) and saline grasslands, b) scrublands, represented mainly by Chilliotrichium diffusum (romerillo) and other species less distributed and c) heaths (sub-shrubs), where Empetrum rubrum (murtilla) stands out [11]. It is important to highlight that 91.8% (24,434.2 km2) of the Patagonian steppe area present in Chile is located in the livestock use area of the Magallanes region and the Chilean Antarctic [11].
3. Grazing systems in Patagonian grasslands
The soils in the grazing fields in the region de Magallanes in Southern Chile are glacial and fluvio-glacial, with sandy-loam and loam-clay-sandy textures and a shallow surface soil horizon with mid to high organic matter content. The soils classification is dominated mainly for mollisols, but also histosols, inceptisols, espodosols and aridisols. Mineralization is very slow, implying severe nitrogen deficiency, also phosphorus and sulfur are limiting factors; pH values range from west to east from less than 4.8 rising to 7.7 where topography favors humidity and the accumulation of salts [11]. The photoperiod in summer is 12–14 hours/day, favorable for most long-day grasses. Dominant vegetation includes 32.7% of native shrubs and tussock grasses (Chiliotrichium diffusum – Festuca gracillima); 26.9% of tussock and naturalized grasslands (Festuca spp, Poa spp); 12.2% of dense shrubs (Ch. diffusum-Empetrum rubrum) and 16.5% forests (Nothofagus pumilio). Sown and improved pastures (T. repens; D. glomerata; Festuca spp) comprise 2.5% of the total area, and about 5% is scattered highly productive humid areas or wetlands (also called vegas) of glacial and morrenic origin (graminoids). The mean nutritive value of native grasslands is low (roughly less than 9% protein and 8.75 MJ EM/kg DM) but selectivity and seasonal variations allow an extensive grazing system sustaining at present over 1,570,000 sheep [12] and 100,000 cattle [7].
3.1 Patagonian grazing systems
Sub-Antarctic rangelands were originally dominated by dense high tussocks (Festuca sp.) and less palatable shrubs. However, after the onset of the sheep industry, stock numbers rose to about 3 million by mid-20th century [13] and the grazing vegetation community shifted, first towards short tussocks and an inter-tussock cover of dense, low stature grasses and geofites, and later towards growing patches of invaders such as Taraxacum sp., Agrostis sp., Aira sp. or Hieracium sp. and even bare soil following the humidity gradient. In contrast, wetlands are dominated by more palatable species [14, 15] with higher growth rates in comparison to the sites dominated by F. gracillima [16].
The extensive grazing management in Patagonia (Magallanes region in Chile and Southern Patagonia in Argentina) is defined as a seasonal continuous grazing system, with summer set-stocking on paddocks above 150 m of altitude. Early on, grazing was adapted for wool production, a productive system with lower nutritional demand. The productive system has since shifted towards meat production, increasing the nutritional requirements of sheep due to the pregnant ewe and lamb raising [17]. Considering an estimation of dry matter consumption by an ewe of 50 kg live weight raising one lamb is around 650 kg DM year−1.
The Sub-Antarctic rangelands (also called coironales) have an herbage mass production between 33 and 1439 kg DM ha−1 year−1 (depending on edaphoclimatic condition and grazing management) and are dominated by F. gracillima [16], a low palatability tussock species with low nutritional value that does not fulfill the minimum requirements of energy and protein for sheep maintenance and growth [18]. By comparison, wetlands or valley greens in Magallanes represent just 5% of the total productive surface with herbage mass production that ranges from 500 kg DM to 11,000 kg DM ha year−1 [16, 19]. These differences are due to the wetland’s intrinsic properties [14, 20] and poor farm organization to do not separately fence wetlands from the less productive sites (rangelands dominated by F. gracillima), leading to overgrazing due to continuous use, and increasing the heterogeneity within and between paddocks due to selective grazing [21], increasing the risks of soil erosion and ecosystem degradation for both rangelands and wetlands. Therefore, due to their difference in growth potential, rangelands dominated by F. gracillima need to be managed from an extensive management approach whereas wetlands are more adapted to an intensive use [17].
3.1.1 Continuous grazing system
Extensive pasture size and large herd numbers (thousands of animals), combined with the climatic conditions and cultural traditions, have led to seasonal continuous grazing being the most common livestock production management approach. This extensive management system is characterized by large paddocks of hundreds of hectares, designed to separate stock categories rather than to target defoliation periods. The defoliation period is determined by season, sheep physiological periods and location of the grazing sites. In sub-Antarctic rangeland, snow cover determines when and where herds graze. The grazing year is split in two periods, with summer grazing from December to May in wetlands or sites with altitudes of 150 m above sea level or greater. Winter grazing occurs from May to December in lower altitude sites with a more favorable temperature range during the coldest months [17, 22]. Winter grazing generally overlaps with lactation and postpartum periods [22, 23].
Even though the disadvantages of continuous grazing in highly productive livestock systems are clear, in low-producing rangelands, the disadvantages are more ambiguous. It has been indicated in medium and long-term experiments [24] continuous grazing with the correct stocking rate, calculated based on herbage mass production, is an effective way to control desertification and achieve good animal performance [24, 25]. However, it is recognized that continuous grazing can increase heterogeneity [25] and weed invasion [26] on overgrazed sites.
Sheep actively select preferred species based on plant phenology (tender shoots and new regrowth, flowers and fruits) thus, in continuous grazing management, sheep overgraze the more palatable material, under grazing or leaving untouched older shoots. Recommended grazing practices imply an even, controlled defoliation height, followed by a specific regrowth period. The latter is supported by physiological plant research performed in several species [27, 28, 29, 30, 31], suggesting that, independent of the grazing system or ecosystem evaluated, vegetative species, particularly forage species, depend on energy reserves to regrow following defoliation [32] and to survive after drought periods [33]. Thus, selectivity must be avoided through careful estimation of grazing pressure. This requires more, smaller paddocks of similar vegetative communities, and strict control of grazing frequency. Animal nutrition must be considered, since enforcing the consumption of low nutritive value material may not be tolerated by younger or pregnant sheep. Modifying the traditional system is a major task implying qualitative and quantitative changes in both labor and mind set.
3.1.2 Rotational grazing
For rotational grazing to be performed, it is necessary to improve farm organization and increase the number of paddocks, separating different vegetative communities, such as wetlands, rangeland and forests, to avoid the negative effects of seasonal continuous grazing [21]. Several types of rotational grazing have been proposed for rangeland grazing management, however, as sheep reproductive phenology has to be considered [23], two of them could be applied in the Magallanes region: 1) rotational deferred grazing; 2) traditional rotational grazing with a high animal density [17, 24, 25].
Rotational deferred grazing: In this system, each paddock is rested for a full year at some point in a multi-year rotation to allow species recovery and reseeding [24] and to recover ecosystem resilience after years of defoliation [25]. There are no clear results in animal performance when rotational deferred grazing is compared to continuous grazing [24]. Furthermore, [25] indicated that in Moy Aike Chico, there were no important differences between a rotational deferred grazing system and continuous grazing in terms of animal production.
Traditional rotational grazing: There have been a few examples in the region with different frequencies and intensities. However, high intensity grazing is not recommended in rangeland settings due to the diminishment in animal performance and the low durability of the rangeland [24]. Grazing with low intensity and short duration at an experimental level (Experimental station Leleque, Southern Patagonia) showed an improvement in animal performance, however, the low growth rates during winter together with a low precipitation, mains factors that limit the herbage growth in Patagonia, meant the resting periods would not be long enough for forage species to recover [25]. There is not enough evidence of the benefits of rotational grazing over continuous grazing in ecosystems with low potential growth under a proper stocking rate [24, 25, 34]. However, rotational grazing showed benefits over continuous grazing in sites with high potential growth such as in sites with higher rainfall or wetlands.
In 2004 a rotational experiment with lambs was carried out on a wetland in Tierra del Fuego. The wetland was excluded from the rest of the paddock and regenerated by direct drilling (zero tillage) with a mix of species including Lolium perenne, Festuca arundinacea, Dactylis glomerata, Trifolium repens and Plantago lanceolata at a seeding rate of 28 kg ha−1 of grasses and 8 kg ha−1 of broadleaf species. Nitrogen, phosphorus, potassium and sulfur were applied at 46–46 – 22 – 22 kg ha−1, respectively. The original botanical composition evaluation identified Azorella trifurcata, a creeping plant without livestock value, as the dominant species. The natural grassland reported an average gross protein value of 40 g kg−1 in. After four seasons, the trend of dry matter production was analyzed. In the first year, approximately 1035 kg DM ha−1 were produced, and the annual average for the next three years was no more than 3600 kg DM ha−1 while the natural grassland in the exclusion zone (5 hectares) produced up to 700 DM kg ha−1 annually during the four seasons. In the last season, lamb liveweight gain after one month of rotational grazing (stocking density of 80 lambs ha−1) was 2.05 kg per lamb moth−1, significantly higher than the gains in the traditional grazing system (1.39 kg per lamb and a stock density of 2 lambs ha−1).
3.2 Future perspective
Modification of the traditional management is imperative to stop the depletion of the ecosystem functioning caused by sheep overgrazing in the Magallanes region. Ecosystem parameters such as vegetation, soil and water have to be considered to reach a sustainable productive system. Remote sensing technologies are an excellent tool for planning and evaluating changes in paddock grazing duration and timing, where University of Magallanes has developed this technology with use of satellite image in the agricultural area of the region from 2003. Also, the study of soil microbiology is an incipient area in development and could be an excellent assistance for soil fertility and grassland production. Efforts to shift the traditional paradigm from a sole focus on animal condition and performance to one that includes ecosystem functioning exist [35]. However, controlled experiments have to be performed to determine the necessary resting periods for the recovery of the rangeland and wetland vegetation, soil and water parameters.
4. Fodder crop
Livestock production in Magallanes depends on rangelands as the main source of food [36]. However, rangeland vegetation alone cannot meet sheep nutritional requirements, especially during peak nutritional demand (for example, the third trimester of pregnancy) [37]. Although wetland areas can provide food in quantity and quality, these are in a state of progressive degradation or are not capable of sustaining an acceptable production throughout the year due to erratic forage production. Since the beginning of sheep production in the region, farmers have seen the need to establish forage crops as a hay source, during critical physiological periods and harsh weather, or for grazing with the objective of increasing lamb weights before slaughter.
Establishment and development of sheep farming began in the Magallanes region during the second half of the 19th century. Large land concessions by the State and investment from private companies allowed the growth of the sector in the southernmost region of Chile [36]. Establishment of forage crops should be considered within its historical context.
In 1976, the Magallanes region had around 248,504.6 ha of sown grasslands, which could be divided between annual crops and permanent grasslands [38]. Ten years later, there were between 104,878 ha [39] and 194,185 ha [40], which were based on the use of forage mixtures such as cocksfoot (Dactilys glomerata), common velvetgrass (Holcus lanatus), white clover (Trifolium repens), monophytic grasslands of common velvetgrass, alfalfa (Medicago sativa), Festuca rubra and Agropyron elongatum. Although the Tierra del Fuego Livestock Society planted 10,000 ha year−1, today the vast majority are missing or in a state of degradation [41].
Current numbers indicate that there are no more than 6,039.2 ha of forage crops, of which the vast majority is alfalfa. However, [42], estimates that there are currently around 9,800 ha of alfalfa in the region. This is because state subsidy programs that begun in 2004 have allowed ranchers to establish fodder crops. Sowing grasslands is a necessity on the part of the agricultural sector and the area devoted to forage crops has been increasing. Although there is a wide range of species and cultivars on the market, only a few are able to establish themselves and produce desired yields due to edaphoclimatic conditions.
Among the most adaptable species are oats (Avena sativa) as the main annual crop and alfalfa and mixed meadows (mixes of cocksfoot -Dactylis glomerata-, tall fescue -Festuca arundinacea- and white clover –Trifolium repens) as permanent meadows. There are two different establishment methods for perennial plantings in Magallanes: a) traditional tillage; b) zero tillage by direct drilling. This last method is unique, but its effectiveness depends on site conditions such as species competition, soil humidity and soil depth. Some examples of typical direct drilling in the region are alfalfa on tussock steppe (without use of herbicide) and mix of grasses with white clover on meadows.
Rainfall during the growing season strongly influences yields since regional production is based on dryland systems with no irrigation, but there is an incipient advanced irrigation technologies as center pivot in Tierra del Fuego. The current varieties of oats have yields that can range between 5,000 and 10,000 kg DM ha−1 [43, 44]. Other annual crops such as hybrid rye can produce between 8,000–12,000 kg DM ha−1 [45]. Cocksfoot can yield from 3,000 to 7,000 kg DM−1 in the third year from the establishment, while tall fescue can produce 4,000–6,000 kg DM ha−1.
Without a doubt, alfalfa is the main forage crop in the Magallanes region. This species is preferred because of its ability to establish itself in the vast majority of the soils and climatic districts of Magallanes (Figure 2). Fall dormancy level 3–4 varieties capable of going into dormancy in the autumn-winter months are used. At least three years are required for the crop to enter full production, increasing forage production from 400 kg DM ha−1 [46] in the first year to a potential of 12,000 kg DM ha−1 [47].
Figure 2.
Fodder crop of Alfalfa in Torres del Paine, Magallanes region (Image by Jorge Ivelic-Sáez).
Management of forage crops in Magallanes is based, normally, on cutting for hay or silage during December and January. In March and April, following regrowth, fields are grazed in order to increase the weight of lambs before slaughter.
5. Artificial insemination
Farm productivity depends on each sheep producing at least one lamb each year. The use of natural service during the breeding period is the most common practice in commercial Magallanes farms. However, since the 1970s, artificial insemination (AI) has been part of the production system, especially in stud farms, in order to accelerate the genetic progress and the production of flock replacements (males and females).
5.1 Artificial insemination: a productive tool
AI has been used mainly in genetic and selection programs, in order to improve the commercial traits of interest [48]. For dual purpose breeds such as Corriedale, increasing fleece weight, reducing fiber diameter, and augmenting lamb weight at weaning are normally the traits to be improved via introduction of animals with a higher genetic value [49]. In Merino animals, fleece weight and reduced fiber diameters are the main selection traits. Among the different alternatives, intracervical AI using fresh semen is the most widely used AI technique.
5.1.1 Preparing the animals for artificial insemination with fresh semen
Selection of males is the first step in AI programs. Regardless of the origin (self-produced or acquired from a sheep stud farm), rams will be selected according to their phenotypic and productive characteristics. Genital tract soundness, evaluation for brucellosis (Brucella ovis), and conformation of legs, hoofs, and mouth, are normally checked by the farmer at least one month before the onset of the reproduction season. A good body condition and body weight will also be checked prior to the AI program as it influences the reproductive efficiency of animals [50], particularly prolificacy in Magallanes [51]. Similarly, females selected as recipients will be checked for body condition and any health issues, paying special attention to age, teeth, mouth and udder conformation and soundness.
5.1.2 Estrus synchronization protocols
Different estrus synchronization protocols are used in Magallanes selected based on factors such as labor, cost and efficiency. Although some producers may use the natural estrus, two options of synchronization are commonly utilized. The first one is the use of prostaglandin analogs in one or 2 doses, separated by 11–12 days [52]. The second one uses progestogens in the form of sponge pessaries or CIDR devised, used for 11 to 14 days available in the market with estrus concentration of 90% of the animal in 81 h after sponge withdrawal [53]. A protocol using equine chorionic gonadotrophin (eCG) hormone at the time of CIDR withdrawal is normally used to improve ovulation rate and fertility [54].
5.1.3 Artificial insemination facilities in Patagonia
Due to cold weather conditions, the use of indoor facilities is highly recommended. The basic infrastructure is a room for semen extraction, with a head stock for a female in heat, and a lower area for the personnel to have a better access to the ram penis. Lubricant gel, warmed water and artificial vagina for practicing, are the basics for obtaining semen. After semen collection, quality evaluation (e.g., volume, concentration, motility, etc.) and dilution takes place. This occurs in the lab area, where room temperature is maintained between 20 and 25°C. Access to the sheep in heat is through a window located at the height of the vulva, with the operator standing in an insemination pit in the floor of the lab and barn, and the ewes will be transported in a trolley with wheels on rails.
5.1.4 Fresh semen artificial insemination
Regardless of the synchronization protocol, the use of teaser rams helps in the identification of ewes in heat. Teaser rams are painted with a mix of edible oil and colored soil in a ratio of 2 liters of oil per 1 kg of soil. The use of a harness with a crayon has been previously evaluated, however; special attention must be paid to crayon selection, since temperatures below 0°C, which are normally observed during the winter, interfere with a good painting of ewes in heat. The mix with oil must follow a soil color gradient, starting with light colors and finishing with dark ones (e.g. yellow, red, blue and finally black) as this allows the identification of animals in different reproductive cycles, which normally lasts between 14 to 17 days.
Females are normally taken into the yards once a day, early in the morning. Those ewes showing a clear rump mark are separated, while those not presenting heat returns to the paddock with the teaser rams. Ewes in heat are artificially inseminated in the afternoon. However, in order to increase pregnancy rates, two checks in the day are recommended, early in the morning and in the afternoon, with ewes being artificially inseminated in the afternoon and the following morning, respectively. Every two or three days, the painting of the teaser rams is redone.
Fertility rates between 60 and 70% can be achieved with this method [48]. During AI the ear tag of each of the ewes is recorded, in addition to ram number and day and time of AI. After AI, ewes are maintained in a quiet place, with access to food and water, before being taken to their paddock. The use of dogs during all process is normally restricted in order to reduce stress in the animals, which could affect fertility.
5.1.5 Frozen semen artificial insemination
Sometimes, the farmer has the opportunity to import frozen semen from different countries (e.g., New Zealand and Australia due to their good sanitary status, similar to Magallanes). If this is the case, the use of intrauterine laparoscopic AI is the best course of action, with the use of eCG (200–300 IU) as a complementary management, to increase ovulation rate and the number of twins, with higher expected genetic potential. Fertility with frozen semen has been calculated to be over 70% [55].
5.2 Management concepts associated to artificial insemination
Good animal nutrition before and after AI reduces stress, and the farmer needs to consider forage quantity and quality, as well as access to water. Ultrasound pregnancy diagnosis is performed 90 days after AI, in order to check for fertility, but more importantly, to identify single- from twin-bearing ewes. Hence, the latter can be supplemented with a high protein (22%) concentrate to reduce lamb mortality at birth [18], which, under Magallanes environmental conditions, can range from 22 to 62%, being higher in twins [56]. All these managements contribute to increased AI success in Magallanes, making the system more productive and sustainable.
6. Breeding, breeds, and management of sheep production system in Magallanes
Since the second half of the 19th century, the establishment and development of sheep ranching began in the southernmost region of Chile, Magallanes. Large land concessions by the State, and an important commitment from private companies allow an accelerated growth of this industry, being sheep an intrinsic part of the local culture until today.
Natural rangelands in the world, which largely dominate the geography of Magallanes, are those areas used mainly for grazing because they cannot be cultivated. In these large rangelands, the grazing system is “extensive”, not only in the sense that it is carried out over large areas, but also because level of inputs, and management of animals is relatively low, with a stocking rate around 0.8 sheep equivalent ha−1.
6.1 Animal and natural resources
The sheep population in Chile is 2,037,516 heads and the 77.1% is located in Magallanes (1,571,056), the southern region of Chile [12]. In this area, sheep production is the most important, and almost the only agricultural industry. It has been developed for the last 145 years (Figure 3).
Figure 3.
Number of sheep in Chile and Magallanes region. Dots in red and blue lines counting data between VI to XII region and farms with higher than 60 sheep [7, 12, 13, 38, 39, 57].
Corriedale is the main breed and represents 55% of the regional stock, just as a purebreed. Some operations have introduced different Merinos, as Australian Merino, MPM (Multi Purpose Merino, developed by an Australian stud, and imported for some breeding seasons into Magallanes), 4 M (Marin Magellan Meat Merino, developed by Marin family in a big sheep operation, from MPM and other Merino lines, and registered officially as the first local purebreed), and most important in recent years the Dohne Merino, and crosses during the last three decades. Because of the increasing value of meat in the total income of sheep business, it is common to see terminal cross use, typically with Suffolk rams but also some Polled Dorset, Texel, and White Suffolk. The regional average weaning percent is below 80%.
Breeding season is in fall, and lambing in spring. The extensive management system with very low inputs, low human intervention, and changing annual climatic conditions leads to erratic results.
Land is owned by medium to large producers. The most common situation are flocks with over 4,000 sheep. The meat and wool market is well developed in Magallanes and strongly oriented to exportation. The region has the potential to increase sheep numbers by at least 30% based on increased production estimates from improving 600,000 ha. of rangeland [58].
6.1.1 Management
Sheep production has traditionally been dual purpose; producing wool and meat, with a carcass average weight for lamb increasing from 10.8 in 1987 to 14.1 in 2020, meanwhile the market is targeting 14 to 16 kg [35].
In this scenario, meat, which at one time in the past was considered a by-product of the wool-focused Magellan sheep industry, today drives the income of sheep ranching in the region. Furthermore, San Isidro Farm (Canepa family) in conjunction with INIA Kampenaike introduced three races of hair sheep (White Dorper, Dorper, Katahdin) in 2012 with a high meat performance.
Sheep operations are based on year-round grazing of private land, with incipient use of strategic supplementation. Most ranches own summer range and winter on separate range (Figure 4). Over half do pre-lambing shearing, and lambing is on pasture at springtime.
Figure 4.
Herding sheep from summer to winter range, Tierra del Fuego (Image by Oscar Strauch).
7. Meat quality
The Magallanes region is not only recognized for its natural parks, such as Torres del Paine, but also for the vast pastoral landscapes and extensive sheep farming developed in this unique environment. The main product is lamb meat, which is exported to different countries, predominately in Asia (China: 45%) and the EEC (Italy: 12%) [59].
Magallanes lamb meat is a grass-fed product that normally comes from young animals (4 to 5 months of age), with an average carcass weight of around 13 kg, raised on natural pastures and maintained, in general, with their mothers until mark time. This gives them a mix of milk and grass nutrition which results in a very interesting product quality. Studies developed by INIA (Agricultural Research Institute), have demonstrated that lamb meat from Magallanes has on average 21% protein content, and a total fat content of 6.4%, which is lower compared to other type of meats. When considering the intramuscular fat (2.5%) and cholesterol (53 mg/100 g), this product may be considered as lean. Tenderness is another remarkable attribute of Magallanes lamb meat, with Warner-Bratzler shear-force results of 1.75 kgf, which positions it as a very tender meat. In addition, it has a similar content for SFA (2900 mg/100 g) to other meats, but a higher PUFA content (628 mg/100 g), compared to some reports in beef. However, the n-6/n-3 ratios (1.3 mg / 100 g) and conjugated linoleic acid (CLA; 25 mg / 100 g) contents represent values that are considered good and desirable from a nutraceutical point of view [60].
7.1 The role of Magallanes lamb meat in human nutrition
The meat of lamb produced in Magallanes is characterized for having a high content of iron (Fe) and zinc (Zn). The average content of Fe for lamb meat in the three different areas of production in Magallanes is 3.9 mg/100 g of meat. This value is significantly higher compared to other meats (Table 1). Similar results are observed for Zn content which, with an average of 4.5 mg/100 g of meat, is superior to the Zn content described for other meats (Table 1).
Meat
Fe
Zn
Magallanes lamb
3.9
4.5
Foal
3.3
2.4
Lamb
2.3
2.4
Chicken
0.8
1.3
Beef
1.9
4.0
Pork
0.9
2.1
Table 1.
Iron and zinc levels in meat from different species (mg/100 g) [61, 62].
Iron is well known for its role in human health and disease, where deficiencies may result in anemia, leading to functional impairments, affecting cognitive development, immunity mechanisms, work capacity, learning ability, and are associated with increased rates of morbidity. Deficiencies during pregnancy may result in higher risk of sepsis, maternal mortality, perinatal mortality, and low birth weight [64]. According to the WHO [65], the iron requirements of 97.5% of individuals, in terms of absorbed iron, are higher in menstruating women (2.38 mg/day), 12–16 year-old girls and boys (2.02 and 1.92 mg/day, respectively), and lactating (1.31 mg/day) and pregnant woman (1.14 mg/day). Therefore, Magallanes meat lamb consumption is an excellent source for these groups to cover their daily iron requirements.
An adequate intake of zinc has critical impacts for human homeostasis, immune function, oxidative stress, apoptosis, and aging. A deficiency, even mild, may lead to arteriosclerosis and anemia [66]. The recommended daily dietary zinc requirement is estimated at 15 mg/day [67, 68]. The consumption of Magallanes lamb meat could certainly help cover this recommendation. In conclusion, the high content of iron and zinc, the low n-6/n-3 ratio and high CLA content, low cholesterol, and tenderness, make Magallanes lamb meat a healthy food with desirable organoleptic characteristics.
8. Wool production
Magallanes was an adequate location for extensive sheep production when wool was a commodity of worldwide importance. Historically, wool was bought in bulk directly on the farm through private deals, but since the 1980s the system has evolved to prices defined by proper conditioning and bale sampling for wool fineness (Table 2 and Figure 5).
Price, yield, and wool stock purchased by Standard Wool Cia. from 1998 to 2021 [63].
In these seasons, many farmers did not sell their wool production for low prices, because of the pandemic situation.
M.T. = metric tons.
Figure 5.
Net and clean wool purchased according to fleeces fibre diameter (season 2018/2019) [69].
Almost the entire wool crop is exported to a world market dominated by China. The wool exportation of Magallanes 50 years ago was 13,000 tons [70], but decreased to 5000 tons in the 2017 season [57]. Table 2 shows the price evolution to higher values while wool stocks have simultaneously trended down in recent years with a mean yield of 65% for Standard Wool Company [63] and Agropat1.
Industry trends towards lamb production and fine wools has changed traditional management from extensive grazing with the dominant Corriedale breed, focused on medium fineness wool production (24.5–31.5 μm and 4.0 kg fleece weight per ewe), to more intensive grazing systems based on dual purpose breeds, focused on lamb production and finer wools. Evaluation and breeding programs to meet shifting market demands have been proposed for different resources availability. In Magallanes there are some Corriedale studs grouped in the Corriedale Breeders Association: El Kark (Kroger family); America (Cardenas family); Jerónima (Vilicic family); Avelina (Menendez family); El Trébol (Maclean family); Tehuel Aike (Almonacid family); Chañarcillo (Gutierrez family); Las Vegas (Retamal family); Maria Isabel (Cavada family)2.
In Magallanes two new Merino crosses breeds have been registered in the past ten years: 4 M Merino (Marin Magellan Meat Merino – Tres Chorrillos farm by Marin family) and PRM (Patagonian Robertson Merino – Tres Hermanos farm by Robertson family), both aiming for finer wool (17–22 μm) and heavier lambs, while maintaining the hardiness of Corriedale. For another side, Dohne Merino has been introduced successfully in the region by Hugo Vera in 2004 (Josefina farm), and has resulted in higher profitability on some farms in comparison to traditional breeds [71]. Figure 5 show fleeces fibre diameter for one season, highlighting the range 26.1 to 28 microns as the main diameter in the region.
Shearing practices have also changed to include two options: (a) traditional timing of post-lambing shearing from the end of December to February; (b) pre-lambing shearing in late August and September. The pre-lambing shearing with positive results in lamb marking, lessened ewe mortality [69] and cleaner fleeces [35], this management arrived late in 80′ by the farmers Carlos García and Ivo Robertson. The tally-hi shearing method used in Magallanes was upgraded by New Zealand technicians. The shearing process starts with animals separated in a corral (Figure 6A) into different categories, and then they are moved into the shed (Figure 6B and C). Subsequently the sheep are sheared (Figure 6D and E), fleeces are cleaned on a table (Figure 6F) and placed into the wool press (Figure 6G) to build the bale (Figure 6H), and finally the wool bales are placed all together where each one has a note with a description of wool type and farm name (Figure 6I) and the ewe is released to outside (Figure 6J).
Figure 6.
The traditional shearing process in Magallanes, different process stages from A to J. (Image by Sergio Radic S.).
9. Lactation curve and cheese production
There is one dairy sheep operation that was set up as a pilot program in the 1990s by the University of Magallanes (coordinated by Sergio Kusanovic) in the city of Puerto Natales (Chilean Patagonia). The program uses East Friesian sheep (from Bolson city in Argentina) and was developed with the goal of cheese production at a local scale. The lactation curve (Figure 7) and cheese production is based on grassland grazing and strategic supplementation with 200 g d−1 of commercial concentrate (15% CP; 2.6 Mcal EM kg DM−1) from flushing two weeks prior to breeding through the breeding period. The sheep are fed under a grazing system in the first 100 days of pregnancy. For the last 50 days of pregnancy, 400 g DM d−1 of alfalfa hay is supplemented [73]. Because the nutritional management is mainly by grasslands, it is a way to develop organic farming, a production method with a specific market focus on products of premium quality and high standards [72].
Figure 7.
Milk yield (dotted green line) in lactation period and body live weight (solid blue line) during the year of East Friesian sheep [72].
The feed ration and body reserve are very important inputs for adequate milk yields in dairy sheep at the end of pregnancy and during lactation. For the latter, in systems that base their feeding management on grasslands, body weight at pregnancy, lambing and lactation may be considered indicators of animal nutritional status and body reserve level.
This initiative developed by the University of Magallanes produces the southernmost cheese of Chile. The higher concentrations of fat, total solids and protein (6.2%), present in sheep milk compared to goat (3.4%) and dairy cattle (3.2%), result in high yields in the production of dairy products [74]. There is a possibility to generate a brand image with this kind of cheese in the Chilean Patagonia. The commercialization of sheep cheese in Magallanes traditionally corresponds to consumers of foreign origin, but also markets to gourmet stores, hotels or restaurants, where there is the highest consumption [75].
10. Best livestock practices and animal welfare in Magallanes
In a highly globalized world characterized by increasing demands by the large international markets, the Magallanes region has some intrinsic advantages, including its geographical location, associated with characteristics of extensive production that allow for reducing the risks associated with animal welfare. Although this system minimizes human-animal interactions (limited number of operations and/or contacts)3, livestock should be managed and overseen by capable personnel to ensure the correct execution of management and create a positive human-animal interaction.
Although the concept of welfare refers to a state of physical and mental health where the animal is in complete harmony with the environment that surrounds it [76], today we focus on “one health”, a concept that entails good management and animal care that leads to good human health and positive collateral outcomes, both economic and social [77].
Animal welfare today is structured on five fundamental domains: adequate nutrition and water availability, health and disease prevention, good environment and provision of opportunities, behaviors and freedom to express them, and finally, mental state, which is determined by the experience of the four former domains, logically resulting in both negative and positive parameters. The complex part for extensive production systems is to find the right moment(s) to apply practical, quick, valid, reliable, and repeatable measuring techniques (direct and indirect indicators, based on the resources or the animal, to evaluate its state and condition) to generate an accurate picture of sheep production today in the Magallanes region.
In order to ensure a livestock sector that is both sustainable and adheres to both national (Law Chile 20380, decree-law numbers 28–29-30) and international requirements, rules, and regulations, the sheep industry, farms and livestock personnel are slowly but satisfactorily developing changes in some practices, especially those related to animal handling and painful procedures (tail docking, castration), where the Good Livestock Practices manual is one of the first to be generated on this subject in the region. It is essential today to have plans that allow for storage of adequate food and water supplies, constant health monitoring, and adequate facilities to minimize and facilitate animal handling in delicate procedures such as transport, herding, and shearing, among others, as well as allowing the manifestation of both natural and normal behaviors during production processes.
Finally, it is highly recommended that the personnel working in production units know and understand the concepts related to sheep management and production, which will result in adequate competence, minimizing risks, injuries and potential processes that generate negative effects in the production chain.
11. Sheep farming and wildlife interactions in Magallanes
The relationship between wildlife and animal production involves ecological interactions such as competition for foraging resources and space, and predation [78]. Wildlife-livestock interactions are mostly assumed to be detrimental to human economic activities, leading to wrong attitudes and prosecution of wild species in areas of coexistence with livestock [78]. The situation of sheep ranching in Magallanes is not different; sheep either compete with wild herbivores or are killed due to carnivore predation. Therefore, producer views towards wild species are generally negative [79, 80]. However, despite the economic importance of sheep production in Magallanes, studies about sheep interactions with wildlife are rather scarce, with more information from Argentinean Patagonia [81, 82].
When sheep ranching arrived in southern South America in the late 19th century [83], guanaco (Lama guanicoe), a large South American camelids and the main wild herbivore of the Patagonian steppe, numbered between 7 and 10 million individuals [84]. Since that time, guanaco have been considered the main competitor for sheep by ranchers [85], and their numbers declined to about 600,000 animals by the end of the 20th century. They currently occupy less than 40% of their original range [86]. The decline in guanaco abundance and distribution is associated with high numbers of sheep and resulting reduction in preferred forage [85]. Extensive sheep ranching seems to have produced an increasing degradation of guanaco habitat due to overgrazing, changes in the structure and composition of vegetation, displacing guanaco and changing their distribution [87]; however, sheep-guanaco interaction outcomes are still controversial [88, 89].
Available information is mostly limited to dietary composition of both species, indicating a large overlap in food items [81, 90]. It is assumed that this large herbivore consumes great amounts of vegetation, the equivalent of two to three sheep. Camelids, however, have low metabolism rates, implying lower food consumption, so the opposite situation should be considered [91]. Although ranchers in Magallanes do not place an economic value on guanaco, they are perceived as an obstacle to domestic sheep production [79]. There are efforts from Chilean government agencies under the Ministry of Agriculture to support the sustainable use of guanaco [92]. After several years of guanaco counts, annual hunting quotas under 3% of estimated guanaco population have been established to give guanaco economic value [92]. Currently, the guanaco population inhabiting productive lands in Magallanes is estimated at 297,844 individuals [93].
Other wildlife that might use similar food resources and space with sheep are herbivorous birds like the lesser rhea (Rhea pennata; [94]) and wild geese (Chloëphaga spp) like the upland goose (C. picta; [95]). However, these herbivorous birds are not seeing as competitors like guanaco because of their smaller size and lower conspicuity. Nonetheless, there is a lack of studies on wild birds interacting with sheep ranching in Magallanes and most of information occurs in Argentinean Patagonia [96] and the Falkland Islands [95].
Similarly, since the advent of sheep ranching in southern Patagonia, large predators, like puma (Puma concolor), and meso predators, like culpeo (Lycalopex culapeus) and gray foxes (L. griseous), have been interacting with sheep ranching in rural Magallanes [97]. This interaction with wild native carnivores generates economic losses to ranchers because puma and foxes are a source of sheep mortality. Additionally, the attack and predation of sheep by domestic dogs is a growing concern worldwide, and Magallanes is not an exception. In Chile, domestic dog predation on livestock lacks legal regulation.
According to official government records, carnivores impact animal production in Magallanes [98]. Between 2012 and 2017, 2259 livestock animals were killed by carnivores, 83% of which were sheep (1887 head) [98]. The majority of those attacks were reported on the Island of Tierra del Fuego (59%). If reported attacks are organized by predator species causing mortality, 78% of attacks corresponded to domestic dogs (55 events) accounting for 1855 predated livestock (82%) [98]. Foxes (Lycalopex spp) were reported to predate 208 livestock (9%), and puma predation on livestock was 1% (13 animals) [98].
Farmers hunt native carnivores despite this activity is illegal in Chile [80]. This situation could be associated to the lack of governmental programs to verify livestock mortality causes and issue compensation of economic loss [80]. Recently, sheep ranches near Torres del Paine National Park, one of the main protected areas in Magallanes, have changed their perception of puma because the presence of this large carnivore is a source of an important touristic activity in the area producing important economic revenues [80]. Other animals that are perceived as harmful for sheep farmers include raptors like southern caracara (Caracara plancus) and buzzard eagle (Geranoaetus melanoleucus), which predate on newborn lambs [99], but there are not formal reports from Magallanes.
It is necessary to differentiate sheep losses because of wildlife from those caused by deficient ranch management. Several sheep ranches seem to have incorrect estimates of appropriate stocking rate density that can cause overgrazing and degradation of the steppe that finally drive to poor animal conditions and economic losses, which is not directly related to the presence of wild herbivores. The importance of large carnivores in overall ecosystem health must be considered before lethal control. Predation prevention methods like night shelters or guard dogs, should also be used where appropriate [100].
12. The agritourism potential in Magallanes: Farm tourism or tourism on farms?
The farms in the Magallanes region have been characterized by developing and preserving an extensive infrastructure, consisting of numerous interrelated buildings to meet the demands and services of a sheep farm, which has historically been extensively developed [101]. Usually the farms are huge estates, hundreds or thousands of hectares in size, and in many of them there are still tools, machinery and furniture typical of the colonizing era from the mid-19th century to the early 20th century [102]. These locations are nestled within natural landscapes that include lakes, rivers and wide landscapes such as the Patagonian steppe, where the horizon and the sky display dramatic sunrises and sunsets. Furthermore, prior to the establishment of these ranches, these sites were inhabited by ancestral peoples who knew the territory and its resources very well [103]. All these conditions provide an ideal setting for agritourism [104] as a way to combine culture, nature, leisure and recreation in a landscape experience.
Tourism on farms in the Magallanes region is emerging and poses opportunities and challenges to innovate in regional economic development. Currently, the offer for tourism on estancias is traditional and restricted to activities typical of nature tourism such as wildlife observation, walks, horseback riding, photography and fishing, among others. To a lesser degree, activities typical of agriculture (Figure 8) are available, such as organic agriculture and observation of traditional tasks such as sheep herding or shearing, among others. Often, but not always, this offer is associated with spending the night in the manor houses itself and tasting local cuisine, so that the experience is complemented by the charm of the architectural heritage and historical legacy [101]. However, this type of tourism faces endemic problems such as seasonality, lack of specialized human resources and poor connectivity. Usually the distances are exaggerated, the accesses are tortuous, and even in many of them digital connectivity problems persist, which makes it difficult to implement online marketing and reservation systems, resulting in a loss of service. In addition, many times the tourist product offered is limited to passive observation experiences, but the tourist storytelling to enrich the visitor’s experience and feed their learning and interest, is absent. Thus, this type of tourism wanders between “farm tourism”, where the central activities are related to the ranch trade [105], or “tourism on farm”, a farm where tourist activities other than the traditional.
Figure 8.
a) Herding of sheep in Magallanes, one of the favorite activities to observe by tourists in estancias in the region (image by Claudio Vidal). b) Sheep bath, as another interesting farm task for tourism (image by Sergio Radic K.).
Today, the particularities of the tourist atlas of the Magallanes territory can be considered counterproductive for the development of farm tourism in isolated areas. The profitability of agritourism as such is low and occurs as a complementary element to other economic activities, but it is not the main one [106]. Tourist concentration is persistently monopolized and overshadowed by Torres del Paine National Park, considered by many to be the gem of Patagonia and the main pole of attraction for regional tourism [107]. Thus, perhaps a relevant option would be the diversification of tourism content on the basis of local identity; generate a local identity to offer a different product, where tourists enjoy and learn about distinctive aspects such as architecture, history, ethnography and rural life. This identity could be re-created from and for the territory, starting from the cultural histories and the memory of the ancestral peoples. There are numerous ethnographic, historical, architectural and family resources [103, 108, 109] to implement a touristic storytelling and generate an “experience scape”, as has happened in other areas of farm tourism [110]. However, tourism research is required to consolidate facts, protagonists, sites and narratives for a continuous valorization of the cultural and natural heritage with potential for the development of tourism, whether it is for farm tourism or tourism on farms.
13. Final comments
After 145 years of sheep production, the Magallanes region has become a characteristic and important territory for sheep industry, and must continue to improve the quality level of products demanded by consumers. Three key points lead the future of the industry in the region: sustainable management, markets, and human resources; but the ability to integrate all these points in the same direction will support farm success. Through technology adoption and sustainable management practices, the industry can achieve soil, water, and grassland conservation and utilize best livestock practices that improve animal welfare and sheep-wildlife interactions. Improving and/or intensifying utilization of a small percentage of each farm (approximately between 2 and 5% depending mainly to stocking rate used and the dry matter production of grasslands) will achieve sustainable and profitable long-term production. Considering the economic side of production in the region, the market currently demands lamb carcasses around 14 to 16 kg and finer wool, between 17 to 22 μm. Then, each decision making must consider existing management and farm production system (meat, wool, or dual purpose) and quality product that can be produced. Broadening market potential through diversification is an important consideration, but must be evaluated within the context of each farm, in this way tourism, dairy products or knowledge of ecosystem services could play a significant role. Finally, human resources need to be specialized to face these challenges, for which technical abilities, undergraduate and postgraduate studies are a key component. The Agricultural and Aquiculture Sciences Department of Magallanes University and the Agricultural Research Institute (Kampenaike Experimental Station) will have an important role in disseminating technical knowledge and providing professional development in our region.
Acknowledgments
This work is derived of the compromise acquired in the memorandum of understanding signed by Agricultural Research Institute (Kampenaike Experimental Station) and University of Magallanes. The authors acknowledge all technicians, students and scientists were involved in each research developed in the region in the last years. The farmers what contribute to the progress and sustainability of sheep production in Magallanes.
Conflict of interest
The authors declare no interest conflict.
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To fully describe sheep farming in the Magallanes region, many topics need to be addressed, including sheep production and management, existing vegetative communities, livestock-wildlife interactions, and economic diversification into agritourism and another sheep industry products. All these give shape to the story of the development of sheep farming in Magallanes, which is important at the regional and national level. 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Sales",slug:"francisco-sales",email:"fsales@inia.cl",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Research Institute of Agricultural Economics",institutionURL:null,country:{name:"Hungary"}}},{id:"428990",title:"MSc.",name:"Raúl",middleName:null,surname:"Lira",fullName:"Raúl Lira",slug:"raul-lira",email:"rlira@inia.cl",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Research Institute of Agricultural Economics",institutionURL:null,country:{name:"Hungary"}}},{id:"428991",title:"MSc.",name:"René",middleName:null,surname:"Muñoz-Arriagada",fullName:"René Muñoz-Arriagada",slug:"rene-munoz-arriagada",email:"rene.munoz@umag.cl",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Magallanes",institutionURL:null,country:{name:"Chile"}}},{id:"428992",title:"Dr.",name:"Paulo",middleName:null,surname:"Corti",fullName:"Paulo Corti",slug:"paulo-corti",email:"pcorti@uach.cl",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Austral University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"428993",title:"Dr.",name:"Nilo",middleName:null,surname:"Covacevich",fullName:"Nilo Covacevich",slug:"nilo-covacevich",email:"covacevichnilo@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"428994",title:"MSc.",name:"Jorge",middleName:null,surname:"Ivelic-Sáez",fullName:"Jorge Ivelic-Sáez",slug:"jorge-ivelic-saez",email:"jorge.ivelic@inia.cl",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Research Institute of Agricultural Economics",institutionURL:null,country:{name:"Hungary"}}},{id:"428995",title:"Dr.",name:"Iván",middleName:null,surname:"Ordoñez",fullName:"Iván Ordoñez",slug:"ivan-ordonez",email:"ivan.ordonez@inia.cl",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Research Institute of Agricultural Economics",institutionURL:null,country:{name:"Hungary"}}},{id:"428996",title:"Dr.",name:"Osvaldo",middleName:null,surname:"Vidal",fullName:"Osvaldo Vidal",slug:"osvaldo-vidal",email:"osvaldo.vidal@umag.cl",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Magallanes",institutionURL:null,country:{name:"Chile"}}},{id:"428997",title:"Mr.",name:"Ricardo",middleName:null,surname:"Echeverría",fullName:"Ricardo Echeverría",slug:"ricardo-echeverria",email:"ricardo.echeverria@umag.cl",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Magallanes",institutionURL:null,country:{name:"Chile"}}},{id:"428998",title:"Dr.",name:"Camila",middleName:null,surname:"Sandoval",fullName:"Camila Sandoval",slug:"camila-sandoval",email:"camila.sandoval.torres@inia.cl",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Research Institute of Agricultural Economics",institutionURL:null,country:{name:"Hungary"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Geographical area and weather",level:"1"},{id:"sec_3",title:"3. Grazing systems in Patagonian grasslands",level:"1"},{id:"sec_3_2",title:"3.1 Patagonian grazing systems",level:"2"},{id:"sec_3_3",title:"3.1.1 Continuous grazing system",level:"3"},{id:"sec_4_3",title:"3.1.2 Rotational grazing",level:"3"},{id:"sec_6_2",title:"3.2 Future perspective",level:"2"},{id:"sec_8",title:"4. Fodder crop",level:"1"},{id:"sec_9",title:"5. Artificial insemination",level:"1"},{id:"sec_9_2",title:"5.1 Artificial insemination: a productive tool",level:"2"},{id:"sec_9_3",title:"5.1.1 Preparing the animals for artificial insemination with fresh semen",level:"3"},{id:"sec_10_3",title:"5.1.2 Estrus synchronization protocols",level:"3"},{id:"sec_11_3",title:"5.1.3 Artificial insemination facilities in Patagonia",level:"3"},{id:"sec_12_3",title:"5.1.4 Fresh semen artificial insemination",level:"3"},{id:"sec_13_3",title:"5.1.5 Frozen semen artificial insemination",level:"3"},{id:"sec_15_2",title:"5.2 Management concepts associated to artificial insemination",level:"2"},{id:"sec_17",title:"6. Breeding, breeds, and management of sheep production system in Magallanes",level:"1"},{id:"sec_17_2",title:"6.1 Animal and natural resources",level:"2"},{id:"sec_17_3",title:"6.1.1 Management",level:"3"},{id:"sec_20",title:"7. Meat quality",level:"1"},{id:"sec_20_2",title:"7.1 The role of Magallanes lamb meat in human nutrition",level:"2"},{id:"sec_22",title:"8. Wool production",level:"1"},{id:"sec_23",title:"9. Lactation curve and cheese production",level:"1"},{id:"sec_24",title:"10. Best livestock practices and animal welfare in Magallanes",level:"1"},{id:"sec_25",title:"11. Sheep farming and wildlife interactions in Magallanes",level:"1"},{id:"sec_26",title:"12. The agritourism potential in Magallanes: Farm tourism or tourism on farms?",level:"1"},{id:"sec_27",title:"13. Final comments",level:"1"},{id:"sec_28",title:"Acknowledgments",level:"1"},{id:"sec_31",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Martinic M. Nociones De Geografía De Magallanes. Ediciones de la Universidad de Magallanes, Punta Arenas; 2001.'},{id:"B2",body:'Fick S, y Hijmans R. WorldClim 2: new 1 km spatial resolution climate surfaces for global land areas. 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Diet, Feeding behaviour and food intake of the upland goose (Chloëphaga picta) and ruddy-headed goose (C. rubidiceps) in the Falkland Islands. Journal of Applied Ecology. 1988; 19783-804. DOI: 10.2307/2403282'},{id:"B96",body:'Antún M, Baldi R, Bandieri LM, D’Agostino RL. Analysis of the spatial variation in the abundance of lesser rheas using density surface models. Wildlife Research. 2018; 45:47-54. DOI: 10.1071/WR16233'},{id:"B97",body:'Nanni AS, Teel T, Lucherini M. Predation on livestock and its influence on tolerance toward pumas in agroecosystems of the Argentine Dry Chaco. Human Dimensions of Wildlife. DOI: 10.1080/10871209.2019.1668987'},{id:"B98",body:'Soto N. Perros bravíos en Magallanes, contexto y marco normativo. In: Comisión de Agricultura, Senado de la República de Chile; 21 January 2019; Valparaíso, Chile.'},{id:"B99",body:'Moreira-Arce D, Ugarte CS, Zorondo-Rodríguez F, Simonetti JA. 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Etnobiológica 3: 1-20.'},{id:"B104",body:'Blanco M. & Riveros H. 2010. El agroturismo como diversificación de la actividad agropecuaria y agroindustrial. In: Desarrollo de los agronegocios y la agroindustria rural en América Latina y el Caribe. Conceptos, instrumentos y casos de cooperación técnica, Instituto Interamericano de Cooperación para la Agricultura.'},{id:"B105",body:'Phillip S., Hunter C. & Blackstock K. 2010. A typology for defining agritourism. Tourism Management 31: 754-758.'},{id:"B106",body:'Blanco M. 2007. Agroturismo en Costa Rica. Retos y Oportunidades. Escuela Centroamericana de Ganadería (ECAG) 40: 25-27.'},{id:"B107",body:'Vidal O.J. 2012. Torres del Paine, ecoturismo e incendios forestales: perspectivas de investigación y manejo para una biodiversidad erosionada. Revista Bosque Nativo 50: 33-39.'},{id:"B108",body:'Prieto A. 1988. Cazadores-recolectores del Istmo de Brunswick. Anales del Instituto de la Patagonia 18: 113-131.'},{id:"B109",body:'Martinic M.B. 2011. Documentos inéditos de la historia de Magallanes: Las vivencias patogénicas de Mateo Ivanovic Sapunar. Magallania 39: 277-299.'},{id:"B110",body:'Mei X.Y., Hagensen A.M.S. & Kristiansen H.S. 2020. Storytelling though experiencescape: Creating unique stories and extraordinary experiences in farm tourism. Tourism and Hospitality Research 20: 93-104.'}],footnotes:[{id:"fn1",explanation:"Cecilia Cavada, Agropat Ltda, Punta Arenas."},{id:"fn2",explanation:"https://www.asogama.com/los-planteles; Peter Maclean (El Trébol) and Cecilia Cavada, Agropat Ltda."},{id:"fn3",explanation:"At least three times per year, for operations (shearing, branding, and breeding)."}],contributors:[{corresp:"yes",contributorFullName:"Sergio Radic-Schilling",address:"sergio.radic@umag.cl",affiliation:'
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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. 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Research in automatic face recognition has been conducted since the 1960s, but the problem is still largely unsolved. Last decade has provided significant progress in this area owing to advances in face modelling and analysis techniques. Although systems have been developed for face detection and tracking, reliable face recognition still offers a great challenge to computer vision and pattern recognition researchers. There are several reasons for recent increased interest in face recognition, including rising public concern for security, the need for identity verification in the digital world, face analysis and modelling techniques in multimedia data management and computer entertainment. In this chapter, we have discussed face recognition processing, including major components such as face detection, tracking, alignment and feature extraction, and it points out the technical challenges of building a face recognition system. 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A new opportunity is obtained using the application of statistical methods for evaluating the performance of the system. Evaluation methods are the yardstick to examine the efficiency and performance of any face recognition system. Methods for performance evaluation seek to distinguish, compare, and interpret the various factors such as characteristics of subjects, location, illumination, and images. In this chapter, we show how to adapt popular performance measures commonly used in face recognition research, including—precision, recall, F-measure, fallout, accuracy, efficiency, sensitivity, specificity, error rate, receiver operating characteristics (ROC). 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The use of social media is ubiquitous and cuts across all age groups, social classes and cultures. However, the increased use of these media is accompanied by privacy issues and ethical concerns. These privacy issues can have far-reaching professional, personal and security implications. Ultimate privacy in the social media domain is very difficult because these media are designed for sharing information. Participating in social media requires persons to ignore some personal, privacy constraints resulting in some vulnerability. The weak individual privacy safeguards in this space have resulted in unethical and undesirable behaviors resulting in privacy and security breaches, especially for the most vulnerable group of users. An exploratory study was conducted to examine social media usage and the implications for personal privacy. We investigated how some of the requirements for participating in social media and how unethical use of social media can impact users’ privacy. Results indicate that if users of these networks pay attention to privacy settings and the type of information shared and adhere to universal, fundamental, moral values such as mutual respect and kindness, many privacy and unethical issues can be avoided.",book:{id:"8423",slug:"security-and-privacy-from-a-legal-ethical-and-technical-perspective",title:"Security and Privacy From a Legal, Ethical, and Technical Perspective",fullTitle:"Security and Privacy From a Legal, Ethical, and Technical Perspective"},signatures:"Nadine Barrett-Maitland and Jenice Lynch",authors:[{id:"311821",title:"Ph.D. Student",name:"Nadine",middleName:null,surname:"Barrett-Maitland",slug:"nadine-barrett-maitland",fullName:"Nadine Barrett-Maitland"},{id:"311822",title:"Ms.",name:"Jenice",middleName:null,surname:"Lynch",slug:"jenice-lynch",fullName:"Jenice Lynch"}]},{id:"66135",doi:"10.5772/intechopen.85003",title:"Multimodal Biometrics for Person Authentication",slug:"multimodal-biometrics-for-person-authentication",totalDownloads:1353,totalCrossrefCites:1,totalDimensionsCites:4,abstract:"Unimodal biometric systems have limited effectiveness in identifying people, mainly due to their susceptibility to changes in individual biometric features and presentation attacks. The identification of people using multimodal biometric systems attracts the attention of researchers due to their advantages, such as greater recognition efficiency and greater security compared to the unimodal biometric system. To break into the biometric multimodal system, the intruder would have to break into more than one unimodal biometric system. In multimodal biometric systems: The availability of many features means that the multimodal system becomes more reliable. A multimodal biometric system increases security and ensures confidentiality of user data. A multimodal biometric system realizes the merger of decisions taken under individual modalities. If one of the modalities is eliminated, the system can still ensure security, using the remaining. Multimodal systems provide information on the “liveness” of the sample being introduced. In a multimodal system, a fusion of feature vectors and/or decisions developed by each subsystem is carried out, and then the final decision on identification is made on the basis of the vector of features thus obtained. In this chapter, we consider a multimodal biometric system that uses three modalities: dorsal vein, palm print, and periocular.",book:{id:"8423",slug:"security-and-privacy-from-a-legal-ethical-and-technical-perspective",title:"Security and Privacy From a Legal, Ethical, and Technical Perspective",fullTitle:"Security and Privacy From a Legal, Ethical, and Technical Perspective"},signatures:"Ryszard S. Choras",authors:[{id:"151381",title:"Prof.",name:"Ryszard S.",middleName:null,surname:"Choras",slug:"ryszard-s.-choras",fullName:"Ryszard S. 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This chapter presents a comprehensive discussion on some of the existing schemes of intrusion detection based on misuse detection, anomaly detection and hybrid detection approaches. Some future directions of research in the design of algorithms for intrusion detection are also identified.",book:{id:"8423",slug:"security-and-privacy-from-a-legal-ethical-and-technical-perspective",title:"Security and Privacy From a Legal, Ethical, and Technical Perspective",fullTitle:"Security and Privacy From a Legal, Ethical, and Technical Perspective"},signatures:"Jaydip Sen and Sidra Mehtab",authors:[{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen"},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab"}]}],mostDownloadedChaptersLast30Days:[{id:"70973",title:"Social Media, Ethics and the Privacy Paradox",slug:"social-media-ethics-and-the-privacy-paradox",totalDownloads:2582,totalCrossrefCites:3,totalDimensionsCites:8,abstract:"Today’s information/digital age offers widespread use of social media. The use of social media is ubiquitous and cuts across all age groups, social classes and cultures. However, the increased use of these media is accompanied by privacy issues and ethical concerns. These privacy issues can have far-reaching professional, personal and security implications. Ultimate privacy in the social media domain is very difficult because these media are designed for sharing information. Participating in social media requires persons to ignore some personal, privacy constraints resulting in some vulnerability. The weak individual privacy safeguards in this space have resulted in unethical and undesirable behaviors resulting in privacy and security breaches, especially for the most vulnerable group of users. An exploratory study was conducted to examine social media usage and the implications for personal privacy. We investigated how some of the requirements for participating in social media and how unethical use of social media can impact users’ privacy. Results indicate that if users of these networks pay attention to privacy settings and the type of information shared and adhere to universal, fundamental, moral values such as mutual respect and kindness, many privacy and unethical issues can be avoided.",book:{id:"8423",slug:"security-and-privacy-from-a-legal-ethical-and-technical-perspective",title:"Security and Privacy From a Legal, Ethical, and Technical Perspective",fullTitle:"Security and Privacy From a Legal, Ethical, and Technical Perspective"},signatures:"Nadine Barrett-Maitland and Jenice Lynch",authors:[{id:"311821",title:"Ph.D. Student",name:"Nadine",middleName:null,surname:"Barrett-Maitland",slug:"nadine-barrett-maitland",fullName:"Nadine Barrett-Maitland"},{id:"311822",title:"Ms.",name:"Jenice",middleName:null,surname:"Lynch",slug:"jenice-lynch",fullName:"Jenice Lynch"}]},{id:"51031",title:"Face Recognition: Issues, Methods and Alternative Applications",slug:"face-recognition-issues-methods-and-alternative-applications",totalDownloads:11849,totalCrossrefCites:11,totalDimensionsCites:16,abstract:"Face recognition, as one of the most successful applications of image analysis, has recently gained significant attention. It is due to availability of feasible technologies, including mobile solutions. Research in automatic face recognition has been conducted since the 1960s, but the problem is still largely unsolved. Last decade has provided significant progress in this area owing to advances in face modelling and analysis techniques. Although systems have been developed for face detection and tracking, reliable face recognition still offers a great challenge to computer vision and pattern recognition researchers. There are several reasons for recent increased interest in face recognition, including rising public concern for security, the need for identity verification in the digital world, face analysis and modelling techniques in multimedia data management and computer entertainment. In this chapter, we have discussed face recognition processing, including major components such as face detection, tracking, alignment and feature extraction, and it points out the technical challenges of building a face recognition system. We focus on the importance of the most successful solutions available so far. The final part of the chapter describes chosen face recognition methods and applications and their potential use in areas not related to face recognition.",book:{id:"5183",slug:"face-recognition-semisupervised-classification-subspace-projection-and-evaluation-methods",title:"Face Recognition",fullTitle:"Face Recognition - Semisupervised Classification, Subspace Projection and Evaluation Methods"},signatures:"Waldemar Wójcik, Konrad Gromaszek and Muhtar Junisbekov",authors:[{id:"24059",title:"Dr.Ing.",name:"Konrad",middleName:null,surname:"Gromaszek",slug:"konrad-gromaszek",fullName:"Konrad Gromaszek"}]},{id:"71455",title:"Security and Privacy in Three States of Information",slug:"security-and-privacy-in-three-states-of-information",totalDownloads:702,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"In regard to computational context, information can be in either of three states at a time: in transit, in process, or in storage. When the security and privacy of information is of concern, each of these states should be addressed exclusively, i.e., network security, computer security, and database/cloud security, respectively. This chapter first introduces the three states of information and then addresses the security as well as privacy issues that relate to each state. It provides practical examples for each state discussed, introduces corresponding security and privacy algorithms for explaining the concepts, and facilitates their implementation whenever needed. Moreover, the security and privacy techniques pertaining to the three states of information are combined together to offer a more comprehensive and realistic consideration of everyday security practices.",book:{id:"8423",slug:"security-and-privacy-from-a-legal-ethical-and-technical-perspective",title:"Security and Privacy From a Legal, Ethical, and Technical Perspective",fullTitle:"Security and Privacy From a Legal, Ethical, and Technical Perspective"},signatures:"Ebru Celikel Cankaya",authors:[{id:"313853",title:"Dr.",name:"Ebru",middleName:null,surname:"Cankaya",slug:"ebru-cankaya",fullName:"Ebru Cankaya"}]},{id:"68421",title:"Ethical Issues in the New Digital Era: The Case of Assisting Driving",slug:"ethical-issues-in-the-new-digital-era-the-case-of-assisting-driving",totalDownloads:980,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Mobility is associated with driving a vehicle. Age-related declines in the abilities of older persons present certain obstacles to safe driving. The negative effects of driving cessation on older adults’ physical, mental, cognitive, and social functioning are well reported. Automated driving solutions represent a potential solution to promoting driver persistence and the management of fitness to drive issues in older adults. Technology innovation influences societal values and raises ethical questions. The advancement of new driving solutions raises overarching questions in relation to the values of society and how we design technology (a) to promote positive values around ageing, (b) to enhance ageing experience, (c) to protect human rights, (d) to ensure human benefit and (e) to prioritise human well-being. To this end, this chapter reviews the relevant ethical considerations in relation to assisted driving solutions. Further, it presents a new ethically aligned system concept for assisted driving. It is argued that human benefit, well-being and respect for human identity and rights are important goals for new automated driving technologies. 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Some future directions of research in the design of algorithms for intrusion detection are also identified.",book:{id:"8423",slug:"security-and-privacy-from-a-legal-ethical-and-technical-perspective",title:"Security and Privacy From a Legal, Ethical, and Technical Perspective",fullTitle:"Security and Privacy From a Legal, Ethical, and Technical Perspective"},signatures:"Jaydip Sen and Sidra Mehtab",authors:[{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen"},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab"}]}],onlineFirstChaptersFilter:{topicId:"560",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:11,numberOfPublishedChapters:91,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:333,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:11,numberOfPublishedChapters:144,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:125,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:113,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:23,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:12,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:"25",title:"Environmental Sciences",doi:"10.5772/intechopen.100362",issn:"2754-6713",scope:"
\r\n\tScientists have long researched to understand the environment and man’s place in it. The search for this knowledge grows in importance as rapid increases in population and economic development intensify humans’ stresses on ecosystems. Fortunately, rapid increases in multiple scientific areas are advancing our understanding of environmental sciences. Breakthroughs in computing, molecular biology, ecology, and sustainability science are enhancing our ability to utilize environmental sciences to address real-world problems. \r\n\tThe four topics of this book series - Pollution; Environmental Resilience and Management; Ecosystems and Biodiversity; and Water Science - will address important areas of advancement in the environmental sciences. They will represent an excellent initial grouping of published works on these critical topics.
",coverUrl:"https://cdn.intechopen.com/series/covers/25.jpg",latestPublicationDate:"August 8th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:1,editor:{id:"197485",title:"Dr.",name:"J. Kevin",middleName:null,surname:"Summers",slug:"j.-kevin-summers",fullName:"J. Kevin Summers",profilePictureURL:"https://mts.intechopen.com/storage/users/197485/images/system/197485.jpg",biography:"J. Kevin Summers is a Senior Research Ecologist at the Environmental Protection Agency’s (EPA) Gulf Ecosystem Measurement and Modeling Division. He is currently working with colleagues in the Sustainable and Healthy Communities Program to develop an index of community resilience to natural hazards, an index of human well-being that can be linked to changes in the ecosystem, social and economic services, and a community sustainability tool for communities with populations under 40,000. He leads research efforts for indicator and indices development. Dr. Summers is a systems ecologist and began his career at the EPA in 1989 and has worked in various programs and capacities. This includes leading the National Coastal Assessment in collaboration with the Office of Water which culminated in the award-winning National Coastal Condition Report series (four volumes between 2001 and 2012), and which integrates water quality, sediment quality, habitat, and biological data to assess the ecosystem condition of the United States estuaries. He was acting National Program Director for Ecology for the EPA between 2004 and 2006. He has authored approximately 150 peer-reviewed journal articles, book chapters, and reports and has received many awards for technical accomplishments from the EPA and from outside of the agency. Dr. Summers holds a BA in Zoology and Psychology, an MA in Ecology, and Ph.D. in Systems Ecology/Biology.",institutionString:null,institution:{name:"Environmental Protection Agency",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"38",title:"Pollution",coverUrl:"https://cdn.intechopen.com/series_topics/covers/38.jpg",isOpenForSubmission:!0,editor:{id:"110740",title:"Dr.",name:"Ismail M.M.",middleName:null,surname:"Rahman",slug:"ismail-m.m.-rahman",fullName:"Ismail M.M. Rahman",profilePictureURL:"https://mts.intechopen.com/storage/users/110740/images/2319_n.jpg",biography:"Ismail Md. Mofizur Rahman (Ismail M. M. Rahman) assumed his current responsibilities as an Associate Professor at the Institute of Environmental Radioactivity, Fukushima University, Japan, in Oct 2015. He also has an honorary appointment to serve as a Collaborative Professor at Kanazawa University, Japan, from Mar 2015 to the present. \nFormerly, Dr. Rahman was a faculty member of the University of Chittagong, Bangladesh, affiliated with the Department of Chemistry (Oct 2002 to Mar 2012) and the Department of Applied Chemistry and Chemical Engineering (Mar 2012 to Sep 2015). Dr. Rahman was also adjunctly attached with Kanazawa University, Japan (Visiting Research Professor, Dec 2014 to Mar 2015; JSPS Postdoctoral Research Fellow, Apr 2012 to Mar 2014), and Tokyo Institute of Technology, Japan (TokyoTech-UNESCO Research Fellow, Oct 2004–Sep 2005). \nHe received his Ph.D. degree in Environmental Analytical Chemistry from Kanazawa University, Japan (2011). He also achieved a Diploma in Environment from the Tokyo Institute of Technology, Japan (2005). Besides, he has an M.Sc. degree in Applied Chemistry and a B.Sc. degree in Chemistry, all from the University of Chittagong, Bangladesh. \nDr. Rahman’s research interest includes the study of the fate and behavior of environmental pollutants in the biosphere; design of low energy and low burden environmental improvement (remediation) technology; implementation of sustainable waste management practices for treatment, handling, reuse, and ultimate residual disposition of solid wastes; nature and type of interactions in organic liquid mixtures for process engineering design applications.",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"201020",title:"Dr.",name:"Zinnat Ara",middleName:null,surname:"Begum",slug:"zinnat-ara-begum",fullName:"Zinnat Ara Begum",profilePictureURL:"https://mts.intechopen.com/storage/users/201020/images/system/201020.jpeg",biography:"Zinnat A. Begum received her Ph.D. in Environmental Analytical Chemistry from Kanazawa University in 2012. She achieved her Master of Science (M.Sc.) degree with a major in Applied Chemistry and a Bachelor of Science (B.Sc.) in Chemistry, all from the University of Chittagong, Bangladesh. Her work affiliations include Fukushima University, Japan (Visiting Research Fellow, Institute of Environmental Radioactivity: Mar 2016 to present), Southern University Bangladesh (Assistant Professor, Department of Civil Engineering: Jan 2015 to present), and Kanazawa University, Japan (Postdoctoral Fellow, Institute of Science and Engineering: Oct 2012 to Mar 2014; Research fellow, Venture Business Laboratory, Advanced Science and Social Co-Creation Promotion Organization: Apr 2018 to Mar 2021). The research focus of Dr. Zinnat includes the effect of the relative stability of metal-chelator complexes in the environmental remediation process designs and the development of eco-friendly soil washing techniques using biodegradable chelators.",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorThree:null},{id:"39",title:"Environmental Resilience and Management",coverUrl:"https://cdn.intechopen.com/series_topics/covers/39.jpg",isOpenForSubmission:!0,editor:{id:"137040",title:"Prof.",name:"Jose",middleName:null,surname:"Navarro-Pedreño",slug:"jose-navarro-pedreno",fullName:"Jose Navarro-Pedreño",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRAXrQAO/Profile_Picture_2022-03-09T15:50:19.jpg",biography:"Full professor at University Miguel Hernández of Elche, Spain, previously working at the University of Alicante, Autonomous University of Madrid and Polytechnic University of Valencia. Graduate in Sciences (Chemist), graduate in Geography and History (Geography), master in Water Management, Treatment, master in Fertilizers and Environment and master in Environmental Management; Ph.D. in Environmental Sciences. His research is focused on soil-water and waste-environment relations, mainly on soil-water and soil-waste interactions under different management and waste reuse. His work is reflected in more than 230 communications presented in national and international conferences and congresses, 29 invited lectures from universities, associations and government agencies. 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He has developed his research activity in the fields of fauna and soil ecology, and in the treatment of organic waste, having been the founder and principal investigator of the Environmental Biotechnology Group of the University of Vigo.\r\nHis research activity in the field of Environmental Biotechnology has been focused on the development of novel organic waste treatment systems through composting. The result of this line of work are three invention patents and various scientific and technical publications in prestigious international journals.",institutionString:null,institution:{name:"University of Vigo",institutionURL:null,country:{name:"Spain"}}},editorTwo:{id:"60498",title:"Prof.",name:"Josefina",middleName:null,surname:"Garrido",slug:"josefina-garrido",fullName:"Josefina Garrido",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRj1VQAS/Profile_Picture_2022-03-31T10:06:51.jpg",biography:"Josefina Garrido González (Paradela de Abeleda, Ourense 1959), is a doctor in biology from the University of León and a Professor of Zoology at the Department of Ecology and Animal Biology at the University of Vigo. She has focused her research activity on the taxonomy, fauna and ecology of aquatic beetles, in addition to other lines of research such as the conservation of biodiversity in freshwater ecosystems; conservation of protected areas (Red Natura 2000) and assessment of the effectiveness of wetlands as priority areas for the conservation of aquatic invertebrates; studies of water quality in freshwater ecosystems through biological indicators and physicochemical parameters; surveillance and research of vector arthropods and invasive alien species.",institutionString:null,institution:{name:"University of Vigo",institutionURL:null,country:{name:"Spain"}}},editorThree:{id:"464288",title:"Dr.",name:"Francisco",middleName:null,surname:"Ramil",slug:"francisco-ramil",fullName:"Francisco Ramil",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003RI7lHQAT/Profile_Picture_2022-03-31T10:15:35.png",biography:"Fran Ramil Blanco (Porto de Espasante, A Coruña, 1960), is a doctor in biology from the University of Santiago de Compostela and a Professor of Zoology at the Department of Ecology and Animal Biology at the University of Vigo. His research activity is linked to the taxonomy, fauna and ecology of marine benthic invertebrates and especially the Cnidarian group. Since 2004, he has been part of the EcoAfrik project, aimed at the study, protection and conservation of biodiversity and benthic habitats in West Africa. He also participated in the study of vulnerable marine ecosystems associated with seamounts in the South Atlantic and is involved in training young African researchers in the field of marine research.",institutionString:null,institution:{name:"University of Vigo",institutionURL:null,country:{name:"Spain"}}}},{id:"41",title:"Water Science",coverUrl:"https://cdn.intechopen.com/series_topics/covers/41.jpg",isOpenForSubmission:!0,editor:{id:"349630",title:"Dr.",name:"Yizi",middleName:null,surname:"Shang",slug:"yizi-shang",fullName:"Yizi Shang",profilePictureURL:"https://mts.intechopen.com/storage/users/349630/images/system/349630.jpg",biography:"Prof. Dr. Yizi Shang is a pioneering researcher in hydrology and water resources who has devoted his research career to promoting the conservation and protection of water resources for sustainable development. He is presently associate editor of Water International (official journal of the International Water Resources Association). He was also invited to serve as an associate editor for special issues of the Journal of the American Water Resources Association. He has served as an editorial member for international journals such as Hydrology, Journal of Ecology & Natural Resources, and Hydro Science & Marine Engineering, among others. He has chaired or acted as a technical committee member for twenty-five international forums (conferences). Dr. Shang graduated from Tsinghua University, China, in 2010 with a Ph.D. in Engineering. Prior to that, he worked as a research fellow at Harvard University from 2008 to 2009. Dr. Shang serves as a senior research engineer at the China Institute of Water Resources and Hydropower Research (IWHR) and was awarded as a distinguished researcher at National Taiwan University in 2017.",institutionString:"China Institute of Water Resources and Hydropower Research",institution:{name:"China Institute of Water Resources and Hydropower Research",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:10,paginationItems:[{id:"82465",title:"Agroforestry: An Approach for Sustainability and Climate Mitigation",doi:"10.5772/intechopen.105406",signatures:"Ricardo O. 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He received his Ph.D. in Environmental Analytical Chemistry from Assiut University, Egypt, in 1989. His research interest is in analytical and environmental chemistry with special emphasis on: (1) monitoring and assessing biological trace elements and toxic metals in human blood, urine, water, crops, vegetables, and medicinal plants; (2) relationships between environmental heavy metals and human diseases; (3) uses of biological indicators for monitoring water pollution; (4) environmental chemistry of lakes, rivers, and well water; (5) water and wastewater treatment by adsorption and photocatalysis techniques; (6) soil and water pollution monitoring, control, and treatment; and (7) advanced oxidation treatment. Prof. Rashed has supervised several MSc and Ph.D. theses in the field of analytical and environmental chemistry. He served as an examiner for several Ph.D. theses in analytical chemistry in India, Kazakhstan, and Botswana. 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He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:'"Politechnica" University Timişoara',institution:null},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:null,institution:null},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"417317",title:"Mrs.",name:"Chiedza",middleName:null,surname:"Elvina Mashiri",slug:"chiedza-elvina-mashiri",fullName:"Chiedza Elvina Mashiri",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Midlands State University",country:{name:"Zimbabwe"}}},{id:"352140",title:"Dr.",name:"Edina",middleName:null,surname:"Chandiwana",slug:"edina-chandiwana",fullName:"Edina Chandiwana",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Midlands State University",country:{name:"Zimbabwe"}}},{id:"342259",title:"B.Sc.",name:"Leonard",middleName:null,surname:"Mushunje",slug:"leonard-mushunje",fullName:"Leonard Mushunje",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Midlands State University",country:{name:"Zimbabwe"}}},{id:"347042",title:"Mr.",name:"Maxwell",middleName:null,surname:"Mashasha",slug:"maxwell-mashasha",fullName:"Maxwell Mashasha",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Midlands State University",country:{name:"Zimbabwe"}}},{id:"2941",title:"Dr.",name:"Alberto J.",middleName:"Jorge",surname:"Rosales-Silva",slug:"alberto-j.-rosales-silva",fullName:"Alberto J. Rosales-Silva",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"437913",title:"Dr.",name:"Guillermo",middleName:null,surname:"Urriolagoitia-Sosa",slug:"guillermo-urriolagoitia-sosa",fullName:"Guillermo Urriolagoitia-Sosa",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"435126",title:"Prof.",name:"Joaquim",middleName:null,surname:"José de Castro Ferreira",slug:"joaquim-jose-de-castro-ferreira",fullName:"Joaquim José de Castro Ferreira",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Aveiro",country:{name:"Portugal"}}},{id:"437899",title:"MSc.",name:"Miguel Angel",middleName:null,surname:"Ángel Castillo-Martínez",slug:"miguel-angel-angel-castillo-martinez",fullName:"Miguel Angel Ángel Castillo-Martínez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"289955",title:"Dr.",name:"Raja",middleName:null,surname:"Kishor Duggirala",slug:"raja-kishor-duggirala",fullName:"Raja Kishor Duggirala",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jawaharlal Nehru Technological University, Hyderabad",country:{name:"India"}}}]}},subseries:{item:{id:"19",type:"subseries",title:"Animal Science",keywords:"Animal Science, Animal Biology, Wildlife Species, Domesticated Animals",scope:"The Animal Science topic welcomes research on captive and wildlife species, including domesticated animals. The research resented can consist of primary studies on various animal biology fields such as genetics, nutrition, behavior, welfare, and animal production, to name a few. 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A dynamic career research platform which is based on the thematic areas of comparative vertebrate physiology, stress endocrinology, reproductive endocrinology, animal health and welfare, and conservation biology. \nEdward has supervised 40 research students and published over 60 peer reviewed research.",institutionString:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null,series:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517"},editorialBoard:[{id:"258334",title:"Dr.",name:"Carlos Eduardo",middleName:null,surname:"Fonseca-Alves",slug:"carlos-eduardo-fonseca-alves",fullName:"Carlos Eduardo Fonseca-Alves",profilePictureURL:"https://mts.intechopen.com/storage/users/258334/images/system/258334.jpg",institutionString:null,institution:{name:"Universidade Paulista",institutionURL:null,country:{name:"Brazil"}}},{id:"191123",title:"Dr.",name:"Juan 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\r\n\tThis topic will focus on the current challenges and advantages in the diagnosis and treatment of bacterial infections. We will discuss the host-microbiota relationship, the treatment of chronic infections due to biofilm formation, and the development of new diagnostic tools to rapidly distinguish between colonization and probable infection.
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In many cases, these diseases have adapted so well that they have developed efficient resilience methods in the human host and can live in the host for years. Others, particularly some blood parasites, can cause very acute diseases and are responsible for millions of deaths yearly. Many parasitic diseases are classified as neglected tropical diseases because they have received minimal funding over recent years and, in many cases, are under-reported despite the critical role they play in morbidity and mortality among human and animal hosts. The current topic, Parasitic Infectious Diseases, in the Infectious Diseases Series aims to publish studies on the systematics, epidemiology, molecular biology, genomics, pathogenesis, genetics, and clinical significance of parasitic diseases from blood borne to intestinal parasites as well as zoonotic parasites. We hope to cover all aspects of parasitic diseases to provide current and relevant research data on these very important diseases. 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