Agroecological zones of Tanzania.
\r\n\tThis book aims to provide a comprehensive overview for the robotic interaction including dynamic modeling and control aspects in order to provide a guide for designers of robotic controllers. Furthermore, it helps the roboticists to select the right model, control architecture and accordingly design the appropriate control algorithm for robotic interactive task with respect to the implemented robotic technology.
",isbn:null,printIsbn:null,pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"9531ee9c84fd27d3e5f84caf963632b3",bookSignature:"Dr. Ali Leylavi Shoushtari and Prof. Andon Venelinov Topalov",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/8359.jpg",keywords:"Robotic physical interaction, Human - robot interaction, Kinematics, Dynamics, Interactive tasks, Motion planning, Anthropomorphic manipulators, Compliant joint, Back-drivability, Control approaches, Safety in robotic interaction, Soft robotics",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"July 9th 2018",dateEndSecondStepPublish:"July 30th 2018",dateEndThirdStepPublish:"September 28th 2018",dateEndFourthStepPublish:"December 17th 2018",dateEndFifthStepPublish:"February 15th 2019",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"4 years",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"266351",title:"Dr.",name:"Ali",middleName:null,surname:"Leylavi Shoushtari",slug:"ali-leylavi-shoushtari",fullName:"Ali Leylavi Shoushtari",profilePictureURL:"https://mts.intechopen.com/storage/users/266351/images/system/266351.png",biography:"He received his PhD in Biorobotics from Scuola Superiore Sant\\'Anna, Pisa and MSc in Mechatronics from South Tehran Branch, Azad University. During his PhD he designed and developed Bio-inspired inverse kinematic algorithm for anthropomorphic robotic manipulators, and designed and developed a unified motion planning and compliance control framework for upper-arm Neuro-rehabilitation robotic task. Persued research on design, fabrication and modeling or soft origami actuators in Center for Micro-BioRobotics (CMBR), IIT as a postdoctoral researcher. In 2019, the Farm Tech Group joined Wageningen University & Research and is currently working on soft adhesive grippers for delicate crop handling. The project is in collaboration with the Department of Experimental Zoology, WUR to take inspiration from adhesive properties of tree frog fingertip and Department of Physical Chemistry and Soft Matter in order to develop fabrication methods for soft actuators and sensor.",institutionString:"Wageningen University & Research",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Wageningen University & Research",institutionURL:null,country:{name:"Netherlands"}}}],coeditorOne:{id:"147800",title:"Prof.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",profilePictureURL:"https://mts.intechopen.com/storage/users/147800/images/system/147800.jpeg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. He has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:"Technical University of Sofia, branch in Plovdiv",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"22",title:"Robotics",slug:"physical-sciences-engineering-and-technology-robotics"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"247041",firstName:"Dolores",lastName:"Kuzelj",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/247041/images/7108_n.jpg",email:"dolores@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. 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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The vulnerability refereed is that caused by stress and shocks caused by the impacts of climate change [3]. The global weather change has determined the livelihood setups in most developing countries [4]. In the countries with varied ecological gradients and agroecological zones, we expect diverse impacts in the livelihood systems [5]. Tanzania has seven agroecological zones with different soils, rainfalls, temperatures, vegetations, locations, and altitudes just to mention a few [6]. Some of these zones are endowed with diverse natural resources (high potential zones) like fertile soil, water sources, and favorable climate to mention a few, while other zones are poorly endowed (low potential zones). Therefore, the people in diverse zones have different entitlements. Their responses to stress are varied depending on the livelihood assets and vulnerability [7]. In this aspect, vulnerability may refer to lack of asset to absorb shocks and recover from stress. Some of these assets include human, capital, physical, and technology just to mention few. Over the past two decades, most marginal areas (low potential areas) have been experiencing regular food insecurity due to poor crop yields [8]. This situation has been exacerbated by the rainfall variability, that is, change in seasons, erratic rainfalls, and increased droughts, which affects agricultural systems and reduces crop yields. According to Afifi et al. [9], climate change contributes up to 80% of crop failure in most vulnerable agricultural systems in Tanzania.
\nSince the 1990s, a number of wealth research findings have been done in Tanzania to address climate change impacts and its vulnerability. Among these studies are the following: Ahmed et al. [1], Paavola [3], Rowhani et al. [4], Yanda [5], Agrawala et al. [2], Mkonda and He [8], and Afifi et al. [9]. Despite addressing the temporal and spatial variability of climate change, most of these studies have limited focus on the ground exploration between the people living in low potential zones and those in high potential zones. The studies generally execute on how these impacts affect livelihoods but with little magnitudes on the comparison between groups. Climate change is expected to affect African countries in a variety of ways. For example, temperatures in Tanzania and the whole East African region are expected to rise by between 2 and 4°C by 2100, thus shifting agroecological zones in most areas [5, 10]. However, the impacts will be more pronounced in the already affected areas, especially in the semiarid agroecological zones and other marginal areas.
\nPredictions from global circulation models confirm that global warming will have a substantial impact on biodiversity and agricultural systems in Tanzania [11]. The changing weather patterns such as less predictable seasons, increasing events of erratic rainfall, and prolonged drought will stress on the already stressed areas and will threaten the sustainability of agriculture and food security in most parts of Tanzania [12]. Tanzanian rainfall is predicted to increase in areas with bimodal rainfall pattern from 5 to 45%, while decreasing in those with unimodal rainfall patterns from 5 to 15% [4, 13].
\nThe vulnerability is going to increase in areas experiencing decreased rainfall, thus affecting livelihood systems of the dwellers [14, 15]. Soil replenishment through organic matter decomposition cannot simply take place in these areas [16]. Some areas with increasing rainfall may experience temporary floods and loss of soil fertility through leaching and runoff [5]. Under normal conditions, most of the poor people are squeezed in low potential zones due to entitlement failure [17]. As a livelihood strategy, some of these people living in marginal areas migrate to other areas.
\nThey migrate (some with their herds of cattle) to areas with suitable agricultural systems and economic diversification [6, 18, 19, 20]. A good example is Usangu valleys (alluvial plain agroecological zone) which act as a destination of different people, especially pastoralists from other region with stressed environments.
\nAlthough the impacts of climate change have been globally established, there is a need to assess the magnitude of these effects in local conditions and diverse ecological gradients. Therefore, this chapter establishes the differential resiliences to climate impacts based on high and low potential zones. This will even enable climate practitioners and policy analysts to estimate the level of adjustments needed to curb climate impacts [21].
\nTanzania is located on the eastern coast of Africa, south of the equator, between latitudes 1° 00′ S and 11° 48′ S and longitudes 29° 30′ E and 39°45′. The eastern side of Tanzania is a coastline of about 800 km long marking the western side of the Indian Ocean. Tanzania has a total of 945,087 km2, and out of this area, water bodies cover 61,495 km2 which is equivalent to 6.52% of the total area.
\nThe country has about 44 million hectares of arable land. Tanzania has seven agroecological zones (\nTable 1\n). Eastern plateau and mountain blocks; southern highlands; northern highlands/northern rift valley and volcanic high lands, arid lands/central plateau; alluvial Plains/Rukwa-Ruaha rift zone; and semiarid lands/inland sedimentary plateau.
\nZone | \nSub-zones | \nSoil and topography | \nAltitude | \nRainfall (mm/yr) | \nG/season | \n
---|---|---|---|---|---|
1. Coast | \nNorth: Tanga (except Lushoto), Coast, and Dares Salaam | \nInfertile sands on gently rolling uplands Alluvial soils in Rufuji sand and infertile soils | \nUnder 3000 m | \nNorth: bimodal, 750–1200 mm | \nNorth: October–December and March–June | \n
South: eastern Lindi and Mtwara (except Makonde plateau) | \nFertile clays on uplands and river flood plains | \n\n | South: unimodal, 800–1200 mm | \nSouth: December–April | \n|
2. Arid lands | \nNorth: Serengeti, Ngorogoro Parks, and part of Masailand | \nNorth: volcanic ash and sediments. Soils are variable in texture and very susceptible to water erosion | \nNorth: 1300–1800 m | \nNorth: unimodal, unreliable, 500–600 mm | \nMarch–May | \n
Masai Steppe, Tarangire Park, Mkomazi Reserve, Pangani, and Eastern Dodoma | \n|||||
South: rolling plains of low fertility susceptible to water erosion Pangani river flood plain with saline and alkaline soil | \nSouth: 500–1500 m | \nSouth: unimodal and unreliable, 400–600 mm | \n\n | ||
3. Semiarid lands | \nCentral Dodoma, Singida, Northern Iringa, some of Arusha, and Shinyanga | \nCentral: undulating plains with rocky hills and low scarps. Well-drained soils with low fertility. Alluvial hardpan and saline soils in eastern rift valley and Lake Eyasi Black cracking soils in Shinyanga | \nCentral: 1000–1500 m | \nCentral: unimodal and unreliable: 500–800 mm | \nDecember–March | \n
Southern: Morogoro (except Kiliombero and Wami Basins and Uluguru Mts.) and also Lindi and Southwest Mtwara | \nSouthern: flat or undulating plains with rocky hills, moderate fertile loams and clays in South (Morogoro), and infertile sand soils in center | \nSoutheastern: 200–600 m | \nSoutheastern: unimodal: 600–800 mm | \n\n | |
4. Plateaux | \nWestern: Tabora, Rukwa (north and center), and Mbeya | \nWestern: wide sandy plains and rift valley scarps | \n800–1500 m | \nWestern: unimodal, 800–1000 mm | \nNovember–April | \n
North: Kigoma, part of Mara | \nFlooded swamps of Malagarasi and Ugalla rivers have clay soil with high fertility | \n\n | \n | \n | |
Southern: Ruvuma and Southern Morogoro | \nSouthern: upland plains with rock hills Clay soils of low to moderate fertility in south, and infertile sands in north | \n\n | Southern: unimodal, very reliable, 900–1300 mm | \n\n | |
5. Southern and western highlands | \nSouthern: a broad ridge from N. Morogoro to N. Lake Nyasa, covering part of Iringa, Mbeya | \nSouthern: undulating plains to dissected hills and mountains. Moderately fertile clay soils with volcanic soils in Mbeya | \nSouthern: 1200–1500 m | \nSouthern: unimodal, reliable, and local rain shadows, 800–1400 mm | \nNorthern: December–April | \n
Southwestern: Ufipa plateau in Sumbawanga | \nSouthwestern: undulating plateau above rift valleys and sand soils of low fertility | \nSouthwestern: 1400–2300 m | \nSouthern: unimodal, reliable, and 800–1000 mm | \nSouthwestern: November–April | \n|
Western: along the shore of Lake Tanganyika in Kigoma and Kagera | \nWestern: North-south ridges separated by swampy valleys, loam and clay soils of low fertility in hills, with alluvium and ponded clays in the valleys | \nWestern: 100–1800 m | \nWestern: bimodal, 1000–2000 mm | \nWestern: October–December and February–May | \n|
6. Nothern highlands | \nNorthern: Foot of Mt. Kilimanjaro and Mt. Meru Eastern rift valley to Eyasi | \nNorthern: volcanic uplands, volcanic soils from lavas and ash. Deep fertile loams. Soils in dry areas prone to water erosion | \nNorthern: 1000–2500 m | \nNorthern: bimodal, varies widely between 1000 and 2000 mm | \nNorthern: November–January and March–June | \n
Granite Mts. Uluguru in Morogoro, Pare Mts. in Kilimanjaro and Usambara Mts. in Tanga, Tarime highlands in Mara | \nGranite steep mountain side to highland plateaux. Soils are deep, arable, and moderately fertile on upper slopes, shallow and stony on steep slopes | \nGranitic Mts.: 1000–2000 m | \nGranitic Mts.: bimodal and very reliable 1000–2000 m | \nGranitic Mts.: October–December and March–June | \n|
7. Alluvial plains | \nK—Kilomberao (Morogoro) | \nK—cental clay plain with alluvial fans east and west | \n\n | K—Unimodal, very reliable, 900–1300 mm | \nK—November–April | \n
R—Rufuji (Coast) | \nR-wide mangrove swamp delta, alluvial soils, sandy upstream, loamy down steam in floodplain | \n\n | R—Unimodal, often inadequate 800–1200 mm | \nR—December–April | \n|
U—Usangu (Mbeya) | \nU—seasonally flooded clay soils in north, alluvial fans in south | \n\n | U—Unimodal, 500–800 mm | \nU—December–March | \n|
W—Wami (Morogoro) | \nW—moderately alkaline black soils in east, alluvial fans with well-drained black loam in west | \n\n | W | \nW—December–March | \n
Therefore, this study aimed to distinguish the level of vulnerability and proper adaptation strategies between the high and low potential areas of Tanzania [14].
\nIt is obvious that the impact of climate change will continue to affect the biodiversity in most developing countries [22]. These effects are more pronounced and significant in vulnerable agro-biodiversity. IPCC 2014 reports that Tanzania is among the 13 countries in the world which are affected and most vulnerable to the impact of climate change [23]. This is evidenced by the reality seen on the ground. In this sense, climate change has impacted crop production, forest ecology, fishery industry, and livestock just to mention a few [4, 20, 21, 22].
\nFurthermore, climate change has affected crop genetics, the functioning of the soil microbial (due to drought), landscape, and the entire livelihood systems of 75% of the Tanzanian population (i.e., farmers). Basing on our discussion, the people and biodiversity found in low/marginal areas are more stressed than those in high potential zones. The livelihood options of the poor people in the marginal areas are too limited as they entirely depend on the environment [5].
\nCurrently, the environment is stressed and has failed to support the people, thus the people are further subjected into distress. Prospectively, climate change will affect the ecosystem services and agricultural biodiversity, and the magnitude of the impacts will differ according to biophysical characteristics of the particular area [13].
\nThe increase in temperature and decrease in rainfall (including the shift of rainfall pattern) have significant impact to crop production in most developing countries [1, 2, 3, 4, 5]. In most areas of the country, there is significant correlation between the trend of crop production and that of rainfall [3, 4, 5]. In the years with poor yields, there have been incidences of low rainfall.
\nAgricultural systems are affected by drought and erratic rainfall, and therefore, the condition cannot support crop production. Specifically, crop failure has been more pronounced in the semiarid (i.e., Dodoma, Singida, Tabora, Manyara, and Shinyanga regions) due to prolonged drought and poor soil replenishment [2, 13]. Therefore, semiarid is among the marginal areas with excessive drought, crop failure, and food insecurity [3, 24]. As adaptation measure, farmers are advised to use drought-resistant crops and diverse crop varieties which are tolerant to drought [7, 14].
\nFor example, SARO 5 rice varieties have been adopted in some rice-producing areas (such as Kilombero and parts of Kilosa districts) that face frequent droughts. Agronomic practices done in most marginal areas provide insights on how to optimize climate resilience in these areas. The dominant agricultural systems in these areas are monoculture, shifting cultivation, and extensive livestock rearing just to mention a few [21]. These practices have significant impacts to soil and its ingredients [21, 22, 24, 25].
\nHowever, there are limited soil management practices that are sustainably done in these areas [3]. Comparatively, the high potential zones experience little impacts than their counterparts. According to IPCC 2014, Tanzania will experience diverse impacts of climate change in the agriculture sector [23]. It is predicted that rainfall will increase in bimodal rainfall pattern (high potential zone) and decrease in unimodal rainfall pattern (low potential zone), therefore affecting the already stressed areas (low potential zone). In the high potential zone, especially in Eastern Arc Mountain and alluvial plain just to mention few, the natural replenishment of soil fertility through litter and/or organic matter decomposition is high because the microbial processes such as mycorrhizae can adequately perform their functions [26, 27]. Subsequently, carbon sequestration seems to be more significant in these areas [28, 29]. Therefore, these areas become potential for crop production and other livelihood patterns as they support diverse production systems.
\nClimate is among the significant factors in the formation of the soil. Specifically, temperature, rainfall, and atmospheric carbon have specific function in the decomposition of litter and other plant biomass to organic matter [30]. The concentration of atmospheric CO2 increases the growth rate and water-use efficiency of crops and natural vegetation [5]. Subsequently, the increased microbial activity in the soil always leads to the increase in the rates of plant nutrient release (e.g., C, K, Mg, and trace nutrients just to mention a few) from weathering of soil minerals. Similarly, the mycorrhizal activity leads to better phosphate uptake [31].
\nSubsequently, the increase in soil temperature creates a favorable condition for microbial activity. In turn, this increases the rate of organic matter and litter decomposition for forming soil fertility. Among the soil nutrients formed in this process are soil organic carbon, total nitrogen, and soil Olsen-P [27, 30, 31]. These nutrients are significant for plant uptake for growth and increased production. These processes are more pronounced in the high potential zone than in the low potential zone [5, 6, 7].
\nTherefore, high potential zones can produce more crop yields than low potential zones and therefore, the peoples’ livelihoods in these areas are potentially better [3, 4, 5, 6, 7, 8]. For instance, in the northern highland of Tanzania, granite soil is dominant, and this soil is useful for plant growth and improvement of agricultural systems in those areas. Therefore, these two zones have distinct characteristics and they offer diverse livelihood options [15].
\nThe increase and decrease in rainfall have diverse impacts to different landscapes. This brings insight that different landscapes may have different ways to adapt to climate change impacts [7, 8, 9]. Geographically, highland areas have different biophysical characteristics from lowland areas. It is noted that landscape determines the flow of water runoff and infiltration [6]. It is expected that in plain areas with well-drained soil, there will be loss of soil nutrient through infiltration, while in steep slope with compact soil, nutrient will get lost through water runoff [5, 6, 7, 8, 9, 10].
\nThis scenario is expected to be significant in bimodal rainfall where rainfall is expected to increase [6]. In Mvomero and Kilosa districts of Morogoro region, there have been frequent occurrences of floods due to heavy rains [5]. This hazard is propagated by the characteristics of the landscape, that is, highland and lowland. Similarly, landslides and mudflow have been occurring and are significantly expected to occur in these areas [5].
\nBesides, drought is expected to be pronounced in areas with unimodal rainfall pattern [6]. And this will pose effects depending on the landscape of the area. In this aspect, steep slope will experience poor soil formation and thus the area is not favorable for agriculture. Lowland areas may experience less impacts of drought than highland areas [5]. And this brings insights that agricultural potentials may differ between the two areas.
\nBasing on the potentiality of the area (high and low potential zones), lowland areas often receive nutrients and water from highland areas through runoff and therefore improve the agricultural systems of the locality [1, 2, 3]. Highland and steep slope areas might be vulnerable to environmental stress, thus providing less potentials in agricultural systems unless there are other sources of resources, that is, water and soil fertility [6, 7, 8, 9, 10]. To control this, some farmers and institutions have been practicing some farming systems that are ecologically significant to adapt to climate change and impacts related to environmental stresses [1, 2, 3, 4, 5, 6]. Preferably, conservation agriculture has been opted as a possible absorber of these stresses and shocks. The “Matengo” farming systems in Ruvuma region and the “Ngitiri” pasture farming in Shinyanga, just to mention a few, are some good examples of the mentioned conservation agriculture [5, 6, 7, 8, 9].
\nThe increase in temperature at both global and local levels is predicted to impact a wide range of biodiversity, including the extinction of some animals and plant species [7]. The predicted increase in temperature by 1.5–2.5°C will increase the concentration of atmospheric carbon dioxide and eventually affect the ecosystem functions, biotic species, ecological interactions, and water supply. IPCC 2014 predicts that by 2100, the threshold of resilience of most ecosystems is going to be reduced and narrowed naturally [23].
\nAgricultural systems (animal and crop production) are most concerned in this case. Temperature will increase incidences of drought, flooding, wildfire, ocean acidification, eutrophication (especially in Lake Victoria), and pollution just to mention a few. As a response to this, farmers engage in land-use changes and overexploitation of resources to meet their needs [6].
\nBesides, ecosystem services, particularly sources, will be severely affected. However, the magnitude of these impacts will differ depending on the level of vulnerability, that is, high and low potential zones [10]. There will be relief to some agroecological zones (with high potentials) and severe impacts to low potential zones [12, 13, 14, 15, 16]. This will also be based on the ecological gradient and landscape of the area. Losses of biodiversity (agroecological systems) will automatically affect food security and socioeconomic challenges caused by ecological challenges.
\nLivestock rearing, on the other hand, will experience similar impacts. Some genetic breeds which are vulnerable to climate change impacts will be substituted by drought-resistant breeds. In most drought areas of Tanzania, drought-resistant animals have been replacing the vulnerable ones. Camels (i.e., though few) have been adopted instead of goat, sheep, and cow just to mention a few.
\nBasing on the actual and potential impacts of climate change on resources, some adaptation strategies and mechanisms have been adopted to reduce the magnitude of the impacts [3]. Similarly, landscapes have been determining the best use of the land [3, 4, 5, 6, 7, 8]. Previously, highland areas (southern highland of Tanzania) have been used for tea and coffee plantations. However, due to the changing climate, these areas have become warmer than before and therefore are not conducive for these crops.
\nInstead, maize, beans, and other moderate crops have been grown in these areas as paradigm shift [3, 4, 5, 6]. And thus, coffee, tea, and pyrethrum have been grown in small scale or are totally redundant due to change of weather.
\nAdaptive capacity to climate change impacts is varied over space and time. People have diverse capacity to adapt to climate change impacts [15, 16, 17, 18, 19, 20]. Some are vulnerable, while others are resilient and they can recover soon from the impacts. Similarly, the thresholds of adaptive capacity is subject among other things to resource entitlements, that is, human asset, financial asset, physical asset, and technological asset just to mention a few [21, 22, 24].
\nTanzania has identified a wide range of adaptation strategies through National Adaptation Program for Action [6]. The identified adaptations were based on location (ecological gradients), resource endowments, livelihood options, financial assets, and agroecological zone just to mention a few.
\nAltitude and climate were among the other significant factors in this chapter. The main aim of the program was to identify and recommend proper adaptation strategies that would reduce the vulnerability and increase the resilience of the farmers. Meanwhile, the program comes up with the wide range of adaptation option based on the aforementioned factors [24, 25, 26].
\nThe recommended adaptation strategies include the growing of drought-resistant crops such as cassava (
Modern farming techniques, changing cropping calendar, and involvement of nonfarming activities were other adaptation strategies. All these are done to curb food security in the country [5, 6, 7, 8]. Subsequently, the program report shows that there is spatial and temporal variation of onset and cessation of rain and dry seasons [15, 16, 17, 18]. The trend of rainfall and dry season during 1980–2010 shows that it is not statistically significant different (P > 0.05). Thus, erratic rainfall and rain patterns are significant in determining climate impacts.
\nSimilarly, agricultural and research institutes are responsible to review on the current changes and current recommended adaptation strategies. Policies, plans, frameworks, and projects related to agriculture and environment are keen to accommodate adaptation strategies in their action and implementation for sustainable development of both agriculture and environment. Likewise, enhancing ecosystem services (management and payment of ecosystem services) is a suitable approach of strengthening the adaptation strategies [5, 6, 7, 8].
\nBoth abiotic and biotic factors need to be well accommodated in the planning in order to reduce the magnitudes of climate change impacts [26, 27, 28, 29]. Abiotic factors may range from heat, salinity, floods, and drought to mention a few, while biotic factors are all aspects of living organisms found in the environment [6, 7, 8]. For more explanation, see the subsections below which describe specific adaptation approaches.
\nAbout 30% of the Tanzanian land is under arid and semiarid climates, of which its main activities are extensive livestock keeping and some mixed farming [6, 13]. Therefore, livestock is among the major livelihoods and is a tool of increasing resilience from the stress caused by climate change [21]. However, the impacts of climate change have subjected livestock into stress and will continue affecting it. This is more pronounced in most central regions of Tanzania.
\nThis situation dries water sources and affects grasses in the pasture and range land required for animal grazing [26, 27, 28, 29]. In turn, the situation affects most animals, and most of them die due to shortage of pasture and water. From 2008 to date, thousands of animals have died in Manyara (i.e., Kiteto District), Arusha, Shinyanga, Dodoma, and Singida regions due to drought [13, 14, 15, 16, 17, 18]. In this stance, evidences show that cows have been more vulnerable than goats and sheep. Similarly, the increase in temperature stresses the already affected areas and catalyzes the outbreak of disease and pests which affect the animals [5, 6, 7, 8, 9, 10]. As a result, a number of animals have been dying due to diseases and pest [6, 7, 8]. The effects have been more severe to some types of animal breeds/or and species due to differences of the level of tolerance.
\nSome measures have been taken by the government and local people to adjust to stress. The government has been advocating intensive livestock keeping for the purpose of increasing quality and quantity of the product and reducing overgrazing on the already stressed areas [6, 13]. Pastoralists have been shifting from the stressed environment (low potential zone) to areas with pasture and water (high potential zone). The Usangu valley in Mbeya region (high potential zone) has been the actual and potential destination of most pastoral societies [6, 7, 8, 9, 10].
\nThese pastoralists are after water and pasture for feeding their herds. Therefore, planners and policy makers need to integrate this challenge in order to rescue environmental degradation by pastoral societies as well as to reduce the disturbances to pastoralists.
\nIt is obvious that crop production can be the most affected sector by stresses and shocks of climate change [5, 6, 7, 8]. Increased incidences of drought have reduced crop yield massively. A number of studies show that crop production has been significantly affected by climate change impacts [3, 4, 5]. Crop species that need more moisture are more vulnerable than those which need little. Hybrid maize is among those which are less resistant to drought due to that factor.
\nTherefore, a number of crop species have been lost because they can no longer tolerate to the present climate change impacts. As adaptation strategies, resistant crops such as SARO 5 rice species have been adopted to reduce the vulnerability of rice crop [7, 8, 9, 10]. Otherwise, irrigation agriculture has been recommended as a solution to accommodate a wide threshold of crop species.
\nIn Kilombero, Mtibwa, Usangu, and Ruvu Basin, rice production has been growing due to irrigation. However, only 2% of the Tanzanian land potential for irrigation agriculture has been harnessed. Therefore, the vulnerability of crop species varies depending on where it is grown. In high potential zones, the crop breed may have a wide chance to survive than in low potential zones [15].
\nAgriculture provides full livelihoods to more than 75% of the Tanzanians and most of them are living in rural areas [5, 6, 7, 8]. Therefore, it is very important to make sure that adaptation strategies and coping mechanisms to the impacts of climate change are taken into full consideration [1, 2, 3, 4]. Different agroecological zones may have diverse adaptation measures depending on the climate, soil, financial asset, and human asset just to mention a few. It is obvious that low potential areas are the most fragile ecosystems and when mismanaged even the little potentials may get lost [5, 6, 7, 8].
\nTherefore, a wide range of adaptation measures are considered in various areas of the country [5, 6, 7, 8, 9, 10]. Some of the general adaptation measures taken across the country includes shifting cultivation (to more potential areas), adopting drought-resistant crops like cassava (
Another adaptation related to agricultural system is the change of agronomic practices [5, 6, 7, 8, 9, 10, 11, 12]. In this aspect, the adaptation of conservation agricultural practices such as agroforestry, better crop rotation, mixed farming, and intercropping [15, 16, 17, 18, 19, 20] will help to improve organic soil fertility, preferably soil carbon. This will increase crop yields and carbon sequestration of greenhouse gases. This goes together with the adoption of modern farming techniques, particularly irrigation [21, 22, 24, 25, 26]. Tanzania has done very little in irrigation agriculture because it has harnessed only 2% of the total irrigable land.
\nTherefore, there is a need to work on it and increase the land under irrigation in order to curb all aspects of food insecurity in the country and increase the export of agricultural products. Similarly, early planting is adopted to curb the variation of onset and cessation of both rainy and dry seasons [26, 27, 28, 29]. Erratic rainfall and the shift of onset has been a key problem in most areas in the country [15, 16, 17, 18]. Despite the prediction that rainfall will increase in areas with bimodal rainfall pattern, these areas suffer the same problem of paradigm shift of the growing season.
\nIn has been noted that most of the bimodal rainfall pattern have been experiencing unimodal rainfall with a great shift [4, 5, 6, 7, 8]. Meanwhile, experience from the field shows that the amount of rainfall has been changing in a roughly regular pattern. There have been roughly rotating patterns, that a year with low rainfall is followed by the year with high rainfall and vice versa [15, 16, 17, 18, 19, 20]. Therefore, further adaptation strategies are needed to be accommodated as climate continues to change. We need to incorporate strong adaptation measures in the policy in order to curb food insecurity in the country.
\nNonfarming practices can also help to strengthen the resilience of the people [26, 27, 28, 29]. Diversified sectors such as commercial enterprises and employment just to mention a few, can help to reduce the dependence on the already stressed agroecosystems [30, 31, 32, 33]. Therefore, diversification will enable the replenishment of the soil resources tenable for crop production.
\nTraditional agriculture has been in practice even before the Tanzanian independence [5, 6, 7, 8]. Indigenous knowledge has been limited to solve complex challenges posed by climate change. It is obvious that the number of people has been increasing every year and the demand of food has been accruing too [8, 9, 10, 11]. Sustainable agriculture is currently advocated in order to get duo benefits (environmental conservation and increased crop yields) at the same time [1, 2, 3, 4, 5, 6]. It is a great challenge for the country with about 44 million hectares of fertile land; less than 24% of this resource is harnessed while the country experiences usual food shortage [6, 7, 8].
\nThe adoption of modern farming methods especially irrigation agriculture can increase crop yield to curb food insecurity. Agroforestry system is less adopted in the country, compared to its needs. The Eastern Arc Mountain in Tanzania has the potential for agroforestry but it is least harnessed [27].
\nIn addition, Tanzania has a number of hydroecological zones such as the Ruaha, Rufiji, Ruvu, Wami, Ruvuma, Usangu, Pangani, Kilombero, and Malagarasi valleys just to mention a few [6, 7, 8, 9, 10]. These areas have potential for irrigation agriculture, but the actual situation reveals that there is underutilization and mismanagement of these resources [6]. Instead, these valleys have been sources of conflicts between resource users, therefore posing no or little benefit to users [3, 4, 5, 6, 7, 8].
\nTherefore, good agricultural practices need to be adopted to increase crop yields in various areas. It has been obvious that traditional, rain-fed agriculture is a major production technique to the people [27, 28, 29, 30]. Rain-fed agriculture has been vulnerable to the impact of climate change since the 1980s to date [31, 32, 33]. The adoption of sustainable agriculture countrywide can help to reduce the vulnerability and calibrate a quick recovery of the affected areas.
\nTanzanian agroecological zones (i.e., high and low potential zones) experience the impacts of climate change differently. Semiarid areas experience the impacts of climate change more severely than the alluvial plains. This happens because the former is a low potential zone while the latter is a high potential zone. The vulnerability of the people also depends on the resource entitlements and assets they possess. Overall, poor people have little options than the rich people.
\nThe two categories are differentiated by financial assets. It has been obvious that the poor always live in the low potential zone where they get more challenges and therefore they need a quick rescue; otherwise, their livelihood options are limited. Similarly, they can seek livelihood options by inserting more stress to the already affected environments. They move from the stressed areas to other areas where they end up degrading too.
\nThis study recommends that farmers with weak adaptive capacity should be carefully and immediately attended to; otherwise, their livelihood options can further destroy the environment. The increase in awareness to local farmers in searching for sustainable livelihood options would be more secure to the environment. Similarly, relevant policies should clearly include practical adaptations of the vulnerable societies.
\nThe author declares no conflict of interest.
Chronic myeloproliferative disorders are a group of clonal diseases of the stem cell. It is a group of several diseases with some common features. They derive from a multipotential hematopoietic stem cell. A clone of neoplastic cells in all these neoplams is characterized by a lower proliferative activity than that of acute myeloproliferative diseases. In each of these diseases, leukocytosis, thrombocythemia, and polyglobulia may appear at some stage, depending on the diagnosis [1, 2].
The research on interferon has been going on since the 1950s [3]. Then, the attention was paid to its influence on the immune system. It has been noted that it can exert an antiproliferative effect by stimulating cells of the immune system [4]. In 1987, a publication by Ludwig et al. was published, which reported the effectiveness of interferon alpha in the treatment of chronic myeloproliferative disorders [5].
More and more new studies have been showing the effectiveness of interferon alpha in reducing the number of platelets, reducing the need for phlebotomies in patients with polycythemia vera and also in reducing the number of leukocytes. Moreover, interferon reduced the symptoms of myeloproliferative disorders such as redness and itching of the skin. Additionally, it turned out to be effective in reducing the size of the spleen.
Further studies on the assessment of remission using molecular-level response assessments indicate that the interferon action in chronic myeloproliferation diseases targets cells from the mutant clone with no effect on normal bone marrow cells [6].
Over the years, interferon alpha-2a and interferon alpha-2b have been introduced into the treatment of chronic myeloproliferation, followed by their pegylated forms. The introduction of pegylated forms allowed for a reduction in the number of side effects and less frequent administration of the drug to patients. In recent years, monopegylated interferon alpha-2b has been used to further increase the interval between drug administrations while maintaining its antiproliferative efficacy.
The exact mechanism of action of interferon alpha in the treatment of chronic myeloproliferative disease is still not fully understood, but it has an impact on JAK2 (Janus Kinase) signal transducers and activates the STAT signal pathway (Janus Kinase/SignalTransducer and Activator of Transcription).
Interferon alpha binds to IFNAR1 and IFNAR2c, which are type I interferon receptors. Interferon alpha has an impact on JAK2(Janus Kinase) signal transducers and activates the STAT signal pathway. The disturbances in this signaling pathway are observed in chronic myeloproliferative disorders [7].
Interferon inhibits the JAK-STAT signaling pathway by directly inhibiting the action of thrombopoietin in this pathway [8].
So far, three driver mutations have been described in the course of chronic myeloproliferative diseases that affect the functioning of the JAK-STAT pathway.
JAK2 kinase and JAK1, JAK3, and TYK2 kinases belong to the family of non-receptor tyrosine kinases. They are involved in the intracellular signal transduction of the JAK-STAT pathway. It is a system of intracellular proteins used by growth factors and cytokines to express genes that regulate cell activation, proliferation, and differentiation. The mechanism of JAK activation is based on the autophosphorylation of tyrosine residues that occurs after ligand binds to the receptor. JAK2 kinase transmits signals from the hematopoietic cytokine receptors of the myeloid lineage (erythropoietin, granulocyte-colony stimulating factor thrombopoietin, and lymphoid lineage [9].
A somatic G/T point mutation in exon 14 of the JAK2 kinase gene converts valine to phenylalanine at position 617 (V617F) in the JAK2 pseudokinase domain, which allows constitutive, ligand-independent activation of the receptor to trigger a proliferative signal [10].
Mutation of the MPL gene, which encodes the receptor for thrombopoietin, increases the sensitivity of magekaryocytes to the action of thrombopoietin, which stimulates their proliferation [11].
Malfunction of calreticulin as a result of mutation of the CARL gene leads to the activation of the MPL-JAK/STAT signaling pathway, which is independent of the ligand, as calreticulin is responsible, for the proper formation of the MPL receptor. Consequently, there is a clonal proliferation of hematopoietic stem cells [12].
Below, we provide an overview of some clinical studies on the efficacy of interferon in chronic myeloproliferative disorders.
Polycythemia vera (PV) is characterized by an increase in the number of erythrocytes in the peripheral blood.
Polycythemia vera is caused by a clonal mutation in the multipotential hematopoietic stem cell of the bone marrow. The mutation leads to an uncontrolled proliferation of the mutated cell clone, independent of erythropoietin and other regulatory factors. As the mutation takes place at an early stage of hematopoiesis, an increase of the number of erythrocytes as well as of leukocytes and platelets is observed in the peripheral blood. The cause of proliferation in PV independent from external factors is a mutation in the Janus 2 (JAK2) tyrosine kinase gene. The V617F point mutation in the JAK2 gene is responsible for about 96% mutation, and in the remaining cases the mutation arises in exon 12. Both mutations lead to constitutive activation of the JAK-STAT signaling pathway [13].
As a result of the uncontrolled proliferation, blood viscosity increases, which generates symptoms such as headaches and dizziness, visual disturbances, or erythromelalgia. As the number of all hematopoietic cells, including the granulocytes ones, increases, the difficult to control symptoms of their hyperdegranulation may appear, among which gastric ulcer or skin itching is often observed. During the disease progression, the spleen and liver become enlarged.
The most common complication of the disease is episodes of thrombosis, especially arterial one. During the course of the disease, it can also evolve into myelofibrosis or acute myeloid leukemia.
The treatment of PV is aimed at preventing thromboembolic complications, relieving the general symptoms, the appearance of hepatosplenomegaly as well as preventing its progression.
Each patient should receive an antiplatelet drug chronically, and usually acetylsalicylic acid is the choice. Most often, the treatment is started with phlebotomy in order to rapidly lower the hematocrit level. If cytoreductive therapy is necessary, the drugs of first choice are hydroxycarbamide and interferon [2].
However, the research on the mechanism of the action of interferons is still ongoing. In vitro studies with CD34+ cells from peripheral blood of patients diagnosed with polycythemia vera showed that interferon inhibits clonal changed cells selectively. It was found that interferon alpha-2b and pegylated interferon alpha-2a reduce the percentage of cells with JAK2 V617F mutation by about 40%. Pegylated interferon alpha-2a works by activating mitogen-activated protein kinase P38. It affects CD34+ cells of patients with polycythemia vera by increasing the rate of their apoptosis [6].
A case of a patient with PV with a confirmed chromosomal translocation t(6;8) treated with interferon alpha-2b, which resulted in a reduction of the clone with translocation by 50% from the baseline value, was also described [14].
In 2019, the results of a phase II multicenter study were published, which aimed at assessing the effectiveness of recombinant pegylated interferon alpha-2a in cases of refractory to previously hydroxycarbamide therapy. The study included 65 patients with essential thrombocythemia (ET) and 50 patients with polycythemia vera. All patients had previously been treated with hydroxycarbamide and showed resistance to this drug or its intolerance.
The assessment of the response was performed after 12 months of treatment. Overall response rate to interferon was higher in patients diagnosed with ET than in patients with polycythemia vera. In essential thrombocythemia, the percentage of achieved complete remissions was 43 and 26% of partial remissions. The remission rate in ET patients was higher if calreticulin CALR gene mutation was present. Patients with polycythemia vera achieved complete remission in 22% of cases and partial remission in 38% of cases.
Treatment-related side effects that follow to discontinuation of treatment were reported in almost 14% of patients [15].
The duration of response to treatment with pegylated interferon alpha-2a and the assessment of its safety in long-term use in patients with chronic myeloproliferative disorders was the goal of a phase II of the single-center study. Forty-three adult patients with polycythemia vera and 40 patients with essential thrombocythemia were enrolled in the study. The complete hematological response was defined as a decrease in hemoglobin concentration below 15.0 g/l, without phlebotomies, a resolution of splenomegaly, and no thrombotic episodes in the case of PV, and for essential thrombocythemia—a decrease platelet count below 440,000/μl and two other conditions as above. The assessment of the hematological response was performed every 3–6 months. The median follow-up was 83 months.
The hematological response was obtained in 80% of cases for the entire group. In patients with polycythemia vera, 77% of patients achieved a complete response (CR) while 7% a partial response (PR). The duration of response averaged 65 months for CR and 35 months for PR. In the group of patients diagnosed with essential thrombocythemia, CR was achieved in 73% and PR in 3%. The durance of CR was 58 months and PR was 25 months.
The molecular response for the entire group was achieved in 63% of cases.
The overall analysis showed that the duration of hematological remission and its achievement with pegylated interferon alpha-2a treatment is not affected neither by baseline disease characteristics nor JAK2 allele burden and disease molecular status. There was also no effect on age, sex, or the presence of splenomegaly.
During the course of the study, 22% of patients discontinued the treatment, because of toxicity. Toxicity was the greatest at the beginning of treatment. The starting dose was 450 μg per week and was gradually tapered off.
Thus, on the basis of the above observations, the researchers established that pegylated interferon alpha-2a may give long-term hematological and molecular remissions [16].
The assessment of pegylated interferon alpha-2a in group of patients diagnosed with polycythemia vera only was performed. The evaluation was carried out on a group of 27 patients. Interferon decreased the JAK2 V617F allele burden in 89% of cases. In three patients who were JAK2 homozygous at baseline, after the interferon alpha-2a treatment wild-type of JAK2 reappeared. The reduction of the JAK2 allele burden was estimated from 49% to an average 27%, and additional in one patient the mutant JAK2 allele was not detectable after treatment. It can therefore be postulated that the action of pegylated interferon alpha-2a is directed to cells of the polycythemia vera clone [17].
In 2005, the results of treatment by pegylated interferon alpha-2b of 21 patients diagnosed with polycythemia vera and 21 patients diagnosed with essential thrombocythemia were published. In the case of polycythemia vera in 14 patients, PRV-1 gene mutation was initially detected. In 36% of cases, PRV-1 expression normalized after treatment with pegylated interferon alpha-2b. For the entire group of 42 patients, the remission assessment showed that complete remission was achieved in 69% cases after 6 months of treatment. However, only in 19 patients remission was still maintained 2 years after the start of the study. Pegylated interferon alpha-2b was equally effective in patients with PV and ET. The use and the type of prior therapy did not affect the achievement of remission [18].
Another study with enrolled only PV patients included 136 patients. They were divided into two arms. One group received interferon alpha-2b and the other group received hydroxycarbamide. Interferon dosage was administered in 3 million units three times a week for 2 years and then 5 million units two times a week. Hydroxycarbamide was administered at a dose between 15 and 20 mg/kg/day.
In the group of patients treated with interferon, a significantly lower percentage of patients developed erythromelalgia (9.4%) and distal parasthesia (14%) compared with the group treated with hydroxycarbamide, for whom these percentages were respectively: 29 and 37.5%. Interferon alpha-2b was found to be more effective in inducing a molecular response, which was achieved in 54.7% of cases, in comparison with hydroxycarbamide—19.4% of cases, despite the fact that the percentage of achieved general hematological responses did not differ between the groups and amounted about 70%. The 5-year progression free period in the interferon group was achieved in a higher percentage (66%) than in the hydroxycarbamide group (46.7%) [19].
The most recent form of interferon approved by the
Thanks to these changes to the structure of the molecule, it was possible to achieve a significant increase in its half-life. Ropeginterferon can be administered subcutaneously to patients every 14 days. The clinical trials conducted so far have assessed the ropeginterferon dose from 50 micrograms to a maximum dose of 500 microgams administered as standard every 2 weeks. The possible dose change in case of side effects includes not only the reduction of the drug dose itself, but also the extension of the interval between doses. The extension of the dosing interval up to 4 weeks was assessed.
Ropeginterforn was approved in 2019 by the EMA for the use in patients diagnosed with polycythemia vera without splenomegaly, as monotherapy.
Ropeginterferon, like the previous forms of interferons used in treatment, is contraindicated in patients with severe mental disorders, such as severe depression. It is also a contraindication in patients with noncompensatory standard treatment of disorders of the thyroid gland as well as severe forms of autoimmune diseases. The safety profile of ropeginterferon is similar to that of other forms of alpha interferons. The most common side effects are flu-like symptoms [20].
Ropeginterferon has been shown to exhibit in vitro activity against JAK2-mutant cells. The activity of ropeginterferon against JAK2-positive cells is similar to that of other forms of interferons used actually for standard therapy. Ropeginterferon has an inhibitory effect on erythroid progenitor cells with a mutant JAK2 gene. At the same time, it has almost no effect on progenitor cells without the mutated allele (JAK2-wile-type) and normal CD34+ cells. A gradual decrease of JAK2-positive cells was observed in patients with PV during ropeginterferon treatment. The examination was performed after 6 and 12 months of treatment. In comparison, the reduction in the percentage of JAK2 positive cells in patients treated with hydroxycarbamide was significantly lower.
These results may suggest that ropeginterferon may cause elimination of the mutant clone, but further prospective clinical trials are needed to confirm this theory. The evaluation was performed on a group of patients enrolled in the PROUD-PV study who were treated in France [21].
In 2017, a multicenter study was opened in Italy. The study was of the second phase. In total, 127 patients with polycythemia vera were included in the study. All patients enrolled on the study had low-risk PV. The clinical trial consisted of two arms. Patients received phlebotomies and low-dose aspirin in one arm and ropeginterferon in the other arm. The aim of the study was to achieve a hematocrit of 45% or lower without any evidence of disease progression. Ropeginterferon was administered every 2 weeks at a constant dose of 100 μg.
The response to the treatment was assessed after 12 months. The reduction of hematocrit to the assumed level was achieved in significantly higher percentage of patients in the ropeginterferon group than of patients who received only phlebotomies and aspirin. In addition, none of the patients treated with ropeginterferon experienced disease progression during the course of the study, while among those treated with phlebotomies, 8% of patients progressed.
Grade 4 or 5 adverse events were not observed in patients treated with ropeginterferon, and the incidence of remaining adverse event (AE) was small and comparable in both arms. The most common side effects in the ropeginterferon group were flu-like symptoms and neutropenia; however, the third-grade neutropenia was the most common (8% of cases) [22].
One of the most important clinical studies on the use of ropeginterferon was the PROUD-PV study and its continuation: the CONTINUATION-PV study. These were three-phase, multicenter studies. The aim of the study was to compare the effectiveness of ropeginterferon in relation to hydroxycarbamide. The study included adult patients diagnosed with polycythemia vera treated with hydroxycarbamide for less than 3 years and no cytoreductive treatment at all. In total, 257 patients received this treatment. The patients were divided into two groups: those receiving ropeginterferon or the other being given hydroxycarbamide.
During the PROUD-study, drug doses were increased until the hematocrit was achieved below 45% without the use of phlebotomies, and the normalization of the number of leukocytes and platelets was reached.
The PROUD-PV study lasted 12 months. After this time, the patients continued the treatment under the CONTINUATION-PV study for further 36 months. After the final analysis performed in the 12th month at the end of PROUD study, it was found that the hematological response rates did not differ between the ropeginterferon and hydroxycarbamide treatment groups. These were consecutively 43% in the ropeginterferon arm and 46% in the control arm.
However, after analyzing the CONTINUATION- PV study, it turned out that after 36 months of treatment, the rates of hematological responses begin to prevail in the group of patients receiving ropeginterferon, 53% versus 38% in the control group. Thus, from the above data, it can be seen that the response rate to ropeginterferon increases with the duration of treatment [23].
Another analysis of patients participating in the PROUD and CONTINUATION studies was based on the assessment of treatment results after 24 months, dividing patients into two groups according to age (under and over 60 years).
The initial comparison of both groups of patients showed that older patients had a more aggressive course of the disease. Patients over 60 years of age had a higher percentage of cells with a mutant JAK2 allele. They experienced both general symptoms and some complications, such as thrombosis, more frequently. Both patients under 60 years of age and over 60 years of age in the ropeginterferon arm had a higher rate of molecular response, namely 77.1 and 58.7% compared with the HU remission: 33.3 and 36.1%, respectively. Significantly higher reductions in the JAK2 allele were observed in both groups of patients after ropeginterferon treatment: it was 54.8% for younger patients and 35.1% for elderly patients. For comparison, this difference in the group of patients treated with HU was 4.5 and 18.4%, respectively.
What is more, the age did not affect the frequency of ropeginterferon side effects. In addition, the incidence of adverse ropeginterferon disorders was similar to that observed in the hydroxycarbamide group [24].
Essential thrombocythemia is a clonal growth of multipotential stem cells in the bone marrow. The consequence of this is increased proliferation of megakaryocytes in the bone marrow and an increase in the number of platelets in the peripheral blood. The level of platelets above 450,000/μl is considered a diagnostic criterion.
Essential thrombocythemia may progress over time to a more aggressive form of myeloproliferation, i.e., myelofibrosis. The disease can also evolve into acute myeloid leukemia or myelodysplastic syndrome, both with very poor prognosis. Thromboembolic complications are serious, and they concern over 20% of patients. Thrombosis occurs in the artery and venous area. Moreover, in patients with a very high platelet count, above 1,000,000/μl, bleeding may occur as a result of secondary von Willebrand syndrome [1, 2].
The treatment of ET is primarily aimed to prevent thrombotic complications.
In low-risk patients, only acetylsalicylic acid is used. In cases of high-risk patients, hydroxycarbamide is the first-line drug for most patients. Anagrelide and interferon are commonly used as second-line drugs.
Due to the possible effects of hydroxycarbamide of cytogenetic changes in the bone marrow cells after long-lasting usage, some experts recommend the use of interferon in younger patients in the first line. Interferon is also used as the drug of choice in patients planning a pregnancy [25].
The efficacy of pegylated interferon alpha-2a was assessed on the basis of the group of 39 patients with essential thrombocythemia and 40 patients with polycythemia vera.
Of the overall group, 81% of patients were previously treated prior to the study entry. The patients received pegylated interferon alpha-2a in a dose of 90 μg once a week. The dose of 450 μg was associated with a high percentage of intolerance.
In patients with essential thrombocythemia, the complete remission was achieved in 76%, while the overall hematological response rate brought 81%. Moreover, the molecular remission was achieved in 38%, in 14% of cases, JAK2 transcript became not detectable.
Patients diagnosed with polycythemia vera achieved 70% complete hematological remission and 80% general hematological response to treatment. JAK2 transcript was undetectable in 6% of patients. Molecular remission was achieved in 54% of cases.
Pegylated interferon alpha-2a at the dose of 90 μg per week was very well tolerated. In total, 20% of patients experienced a grade of 3 or 4 of adverse reaction, which was neutropenia. In addition, an increase in liver function tests was observed. Grade 4 of AE was not observed among patients who started the treatment with 90 μg/week while grade 3 neutropenia was an adverse event in only 7% of cases [26].
The effect of interferon alpha-2b treatment in patients with ET and PV was investigated. The study was prospective. Some of the results concerning the group of patients with polycythemia vera are presented in the subsection on polycythemia vera. In total, 123 patients with diagnosed essential thrombocythemia participated in the study. All of them received interferon alpha-2b. The patients were divided into two groups depending on the presence of the JAK2 V617F mutation. The enrolled patients were between 18 and 65 years of age. The treatment they received was, sequentially, interferon alpha-2b in the dose of 3 million units three times a week for the first 2 years, after which time the dose was changed into a maintenance dose, which amounted to 5 million units two times a week.
The analysis showed that the patients with the JAK2 V617F mutation present in a higher percentage achieved an overall hematological response as well as a complete hematological response. The overall hematological response was achieved in 83% of patients with JAK2 mutation, and the complete hematological remission was achieved in 23 cases. In the group of ET patients without the JAK2 V617F mutation, overall hematological response was achieved in 61.4%, while the complete hematological remission was achieved in 12 patients. The 5-year progression-free survival was obtained in 75.9% in the JAKV617F group and only in 47.6% without the mutation.
A significant proportion of patients experienced mild side effects. Grade 3 and 4 of adverse events were severe, most of them being a fever. The isolated cases of elevated liver tests and nausea have also been reported [19].
Pegylated interferon alpha-2b in patients with essential thrombocythemia who were previously treated with hydroxycarbamide, anagrelide, and other forms of interferon alpha, however, due to the lack of efficacy or toxicity, the patients required a change of treatment, was assessed. Pegylated interferon alpha-2b turned out to be effective in these cases. It led to the complete hematological remission in 91% of patients after 2 months of therapy, and in 100% of patients after 4 months. However, merely 11 patients participated in the study. Also only two patients required treatment discontinuation due to the side effects such as depression and general fatigue grade 3 [27].
In case of pregnant patients, interferon is currently considered the only safe cytoreductive drug. Over the years, several analyses of the results of interferon treatment during pregnancy have been carried out.
The assessment of 34 pregnancies in 23 women diagnosed with ET was performed retrospectively. All the pregnancies included in the analysis were of high risk. This high risk was associated with a high platelet count above 1,500,000/μl, a history of thrombotic episode, severe microcirculation disorders, or a history of major hemorrhage.
It turned out that the use of interferon allowed the birth of an alive child in 73.5% of cases. There was no difference in efficacy between the basic and pegylated forms of interferon alpha. In pregnancies without interferon treatment, the percentage of live births was only 60%. Moreover, it was not found if the presence of the JAK2 V617F mutation had any influence on the course of pregnancy [28].
An analysis of the course of pregnancy in patients with ET was assessed in Italy. Data from 17 centers were taken into account. Data from 122 pregnancies were collected from 92 women. In patients diagnosed with essential thrombocythemia, the risk of the spontaneous loss of pregnancy is about 2.5 times higher than among the general population. In the contrary to the study quoted above, it was found that the presence of the JAK2 mutation increases the risk of pregnancy loss. The proportion of live births in patients exposed to interferon during pregnancy was 95%, compared with 71.6% in the group of patients not treated with interferon.
The multivariate analysis also showed that the use of acetylsalicylic acid during pregnancy had no effect on the live birth rate of patients with ET [29].
Whatever its form, interferon is the drug of first choice in pregnancy. Hydroxycarbamide and anagrelide should be withdrawn for about 6 months, and at least for 3 months, before the planned conception. Experts recommend the use of interferon in high-risk pregnancies [30]. A Japanese analysis of 10 consecutive pregnancies in ET patients showed 100% live births in patients who received interferon [31].
In myelofibrosis (MF), monoclonal megakaryocytes produce cytokines that stimulate the proliferation of normal, non-neoplastic fibroblasts and stimulate angiogenesis. The consequence of this is the gradual fibrosis of the bone marrow, impaired hematopoiesis in the bone marrow, and the formation of extramedullary location mainly in the sites of fetal hematopoiesis, i.e., in the spleen and the liver.
The production of various cytokines by neoplastic megakaryocytes leads to the proliferation of normal, noncancerous fibroblasts as well as to increased angiogenesis.
Progressive bone marrow fibrosis leads to worsening anemia and thrombocytopenia. On the other hand, the production of proinflammatory cytokines by megakaryoblasts leads to the general symptoms such as weight loss, fever, joint pain, night sweats, and consequently, progressive worsening of general condition.
The prognosis for myelofibrosis is poor. In about 20% of patients, myelofibrosis evolves into acute myeloid leukemia with poor prognosis.
Currently, the only effective method of treatment that gives a chance to prolong the life is allogeneic bone marrow transplantation. However, this method is only available to younger patients.
The goal of treatment of patients who have not been qualified for allotranspalntation is to reduce the symptoms and to improve the patient’s quality of life. In case of leukocytosis cytoreducing drugs, such as hydroxycarbamide, melphalan, or cladribine can be used. They cause a reduction in the number of leukocytes and may, to some extent, inhibit splenomegaly. Interferon alpha has been used successfully for the treatment of myelofibrosis for many years. The results of its effectiveness will be presented below [2].
Currently, the JAK2 inhibitor ruxolitinib is approved for the treatment of myelofibrosis with enlarged spleen in intermediate and high-risk patients. Ruxolitinib reduces the size of the spleen, reduces general symptoms, and improves the quality of life; however, it does not prolong the overall survival of patients [32].
In 2015, the results of a retrospective study were published to compare the histological parameters of the bone marrow before and after interferon treatment. Twelve patients diagnosed with primary myelofibrosis as well as post-PV MF and post-ET MF were enrolled in the study. Patients were treated with pegylated recombinant interferon alpha-2a or recombinant interferon alpha-2b in standard doses. The time of treatment was from 1 to 10 years. Some patients had previously been treated with hydroxycarbamide or anagrelide. In all cases, karyotype was normal. The prognostic factor of Dynamic International Prognostic Scoring System (DIPSS) was assessed at the beginning as well as during the treatment.
Bone marrow cellularity decreased in cases with increased bone marrow cellularity before the treatment. After the interferon treatment, a reduction in the degree of bone marrow fibrosis was found. The parameters, such as the density of naked nuclei and the density of megakaryocytes in the bone marrow, also improved.
It proves that if the JAK2 V617F mutation had been present, DIPSS was decreased after interferon treatment. This relationship was not observed in patients without the JAK2 V617F mutation. The improvement in peripheral blood morphological parameters and the overall clinical improvement correlated with the improvement in the assessed histological parameters of the bone marrow.
Before the initiation of interferon, seven patients had splenomegaly. During the treatment with interferon, the complete resolution of splenomegaly was achieved in 17% of patients (two cases), and its size decreased in 25% (three cases). A good clinical response was achieved in 83% during interferon therapy. There was no significant difference in response between the two types of interferon used [33].
A prospective study was also conducted in patients with low and intermediate-1 risk group myelofibrosis. Seventeen patients were enrolled. Patients received interferon alpha-2b (0.5–3 milion units/three times a week) or pegylated interferon alpha-2a (45–90 μg/week). The duration of therapy was on average 3.3 years.
Most of the patients responded to the treatment. Partial remission was found in seven patients and complete remission in two patients. Moreover, in four cases, the disease was stabilized and in one case the clinical improvement was achieved. Three patients did not respond to treatment at all and progressed to myelofibrosis. Additionally, the assessment in reducing spleen size was performed. At baseline, 15 patients have splenomegaly, nine of them achieved the compete regression of spleen size [34].
However, the efficacy of interferon in the treatment of myelofibrosis appears to be limited only to a less advanced form, when the bone marrow still has an adequate percentage of normal hemopoiesis and the marrow stroma is not significantly fibrotic. In more advanced stages, interferon was not shown to have any significant effect on the regression of the fibrosis process [35].
In 2020, the results of the COMBI study were published. That was a two-phase, multicenter, single-arm study that investigated the efficacy and safety of the combination of ruxolitinib and pegylated interferon alpha. Thirty-two patients with PV and 18 patients with primary and secondary myelofibrosis participated in the study. The patients were at age 18 and older. Remission was achieved in 44% of myelofibrosis cases, including 28% (5 patients) of complete remission. In patients with PV, the results were slightly worse: 31% of remissions, including 9% of complete remissions. Patients received pegylated interferon alpha-2a (45 μg/week) or pegylated interferon alpha-2b (35 μg/week) in low doses and ruxolitinib in doses of 5–20 mg twice a day.
For the entire group of patients (with PV and MF), the initial JAK2 allele burden was 47% at baseline, and after 2 years of treatment with interferon and ruxolitinib, it decreased to 12%.
The treatment toxicity was low. The highest incidence of side effects occurred at initiation of therapy. It was mostly anemia and thrombocytopenia.
The observations from the COMBI study show that, for the combination of interferon in lower doses with ruxolitinib, it may be effective and well tolerated even in the group of patients who had intolerance to interferon used as the only drug in higher doses. The combined treatment improved the bone marrow in terms of fibrosis and its cellularity. It also allowed to improve the value of peripheral blood counts [36].
It is currently known that some of the additional mutations are associated with a worse prognosis in patients with myelorpoliferation, including patients with myelofibrosis. Some of these mutations have been identified as high-risk molecular mutations. These are ASXL1, EZH2, IDH1/2, or SRSF2. Earlier studies have shown their association with a more aggressive course of the disease, worse prognosis, and shorter survival of patients, as well as a poorer response to treatment. Due to their importance, they have been included in the diagnostic criteria of myelofibrosis [37].
It is also known that the presence of driver mutations, i.e., JAK2, CALR, and MPL or triple negativity, may affect the course of myeloproliferation, including the incidence of thromboembolic complications.
The assessment of the influence of driver mutations and a panel of selected additional mutations on the effectiveness of interferon treatment in patients with myelofibrosis was performed on a group of 30 patients. Only the patients with low- and intermediate-1-risk were enrolled in the study. The treatment with pegylated interferon alpha-2a or interferon alpha-2b resulted in a complete remission in two patients and partial remission in nine patients. The disease progressed in three cases. One patient relapsed and four died. The remaining patients achieved a clinical improvement or disease stabilization. In the studied group, it was not found if the effectiveness of interferon treatment was influenced by the lack of driver mutations. Among the group of four patients with additional mutations, two died and one had disease progression. It was a mutation of ASXL1 and SRSF2. The treatment with interferon in patients without additional molecular mutations in the early stages of the disease may prevent further progression of the disease [38].
The side effects of interferon in the group of patients with myelofibrosis are similar to those occurring after the treatment of other chronic myeloproliferative diseases. The most frequently described are hematological toxicity- anemia and thrombocytopenia, less often is the appearance of leukopenia. Hematological toxicity usually resolves with dose reduction or extension of the dose interval. The most frequently nonhematological toxicity was fatigue, muscle pain, weakness, and depression symptoms. All symptoms are usually mild and do not exceed grade 2 [38].
However, the use of interferon in the treatment of myelofibrosis has not been recommended as a standard therapy. Interferon is still being evaluated in clinical trials, or it is used in selected patients as a nonstandard therapy in this diagnosis.
Mastocytosis is characterized by an excessive proliferation of abnormal mast cells and their accumulation in various organs.
The basis for the development of mastocytosis is ligand-independent activation of the KIT receptor, resulting from mutations in the KIT proto-oncogene. The KIT receptor is a trans membrane receptor with tyrosine kinase’s activity. Its activation stimulates the proliferation of mast cells. That excessive numbers of mast cells infiltrate tissues and organs and release mediators such as histamine, interleukine-6, tryptase, heparin, and others, which are responsible for the appearance of symptoms typical of mastocytosis. In addition, the infiltration of tissues for mast cells itself causes damage to the affected organs.
The prognosis of mastocytosis depends on the type of the disease. In the case of cutaneous mastocytosis (CM), in the majority of cases prognosis is good and the disease does not shorten the patient’s life, but in aggressive systemic mastocytosis (ASM), the average follow-up is about 40 months. Mast cell leukemia has a poor prognosis with a median follow-up of approximately 1 year.
Systemic mastocytosis usually requires the implementation of cytoreductive therapy. The first line of therapy is interferon alone or its combination with corticosteroids. In aggressive systemic mastocytosis, the first line in addition to interferon 2-CdA can be used. An effective drug turned out to be midostaurin in the case of the present KIT mutation. In patients without the KIT D816V mutation, treatment with imatinib may be effective. In the case of mast cell leukemia, multidrug chemotherapy is most often required, as in acute leukemias, followed by bone marrow transplantation [39].
Systemic mastocytosis requiring treatment is a rare disease, this is why the studies available in the literature evaluating various therapies concern mostly small groups of patients.
In 2002, the French authors presented their experiences on the use of interferon in patients with systemic mastocytosis. They included 20 patients. The patients received interferon alpha-2b in gradually increased doses.
The patients were assessed after 6 months. In cases in which bone marrow was infiltrated for mast cells at baseline, it still remained infiltrated after 6 months of treatment.
However, the responses were obtained in terms of symptoms related to mast cell degranulation. Partial remission was achieved in 35% of patients and minor remission in 30%. It concerns mainly skin lesions and vascular congestion. Moreover, the assessment of the histamine level in the plasma revealed a decrease of it in patients who previously presented symptoms related to the degranulation of mast cells, such as gastrointestinal disorders and flushing.
A high percentage of side effects were found during treatment. They concerned 35% of patients. Depression and cytopenia were most frequent ones [40].
Another analysis was a report of five patients with systemic mastocytosis treated with interferon and prednisolone. All patients received interferon alpha-2b in a dose of 3 million units three times a week and four patients additionally received prednisolone. Four patients responded to interferon treatment at varying degrees. One patient, who at baseline had bone marrow involvement by mast cells in above 10%, progressed to mast cell leukemia. In two patients, the symptoms C resolved completely and in one of them they partially disappeared. In one case, stabilizing disease was achieved [41].
In 2009, a retrospective analysis of patients treated with cytoreductive therapy due to mastocytosis was published. The authors collected data from 108 patients treated at the Mayo Clinic. This analysis allowed for the comparison of the efficacy of four drugs used in systemic mastocytosis. There were interferon alpha alone or in the combination with prednisone—among 40 patients, hydroxycarbamide—among 26 ones, imatinib—among 22 persons, and 2-chlorodeoxyadenosine (2-CdA)—among 22 patients.
After dividing the patients into three additional groups on the basis of the type of mastocytosis—indolent systemic mastocytosis, aggressive systemic mastocytosis, and systemic mastocytosis associated with another clonal hematological nonmast cell lineage disease (SM-AHNMD)—the effectiveness of each of type of therapy was assessed.
The highest response rates in indolent and aggressive mastocytosis were achieved with interferon treatment. They were 60% of the responses in both groups, and in the SM-AHNMD group of patients, the percentage was also one of the highest and amounted to 45%. The second most effective drug was 2-CdA. The response rates were 56% for indolent MS, 50% for aggressive MS, and 55% for SM-AHNMD. The patients treated with imatinib achieved response in 14, 50, and 9% by following groups, respectively. In contrast, patients with indolent and aggressive systemic mastocytosis did not respond to hydroxycarbamide treatment at all. The response rate in both groups was 0%. However, patients with MS associated with another clonal hematological nonmast cell lineage disease achieved 21% response to hydroxycarbamide. Additionally, it was found that only interferon relieved symptoms caused by the release of inflammatory mediators by mast cells.
The additional analysis showed no influence of the TET 2 mutation on the response to treatment [42].
In the literature, there are also single cases of mastocytosis presenting trials of nonstandard treatment. That is description of a patient with systemic mastocytosis with mast cell bone marrow involvement. Mutation of c-kit Asp816Val was present. Patient progressed despite treatment with dasatinib and 2-chlorodeoxyadenosine. The patient developed symptoms related to the degranulation of mast cells and increased ascites.
The patient was treated with pranlukast, which is an anti-leukotriene receptor antagonist due to an asthma episode. The rate of ascites growth decreased significantly after one administration. The patient required paracentesis every 10 days and not every 3 days, as before starting to take the drug. After 15 days of treatment with pranlukast, the patient received interferon alpha, which resulted in complete regression of ascites, resolution of pancytopenia, and complete disappearance of the c-kit mutation clone. The infiltration of mast cells in the bone marrow significantly decreased [43].
Interferon alpha was also effective in a patient with systemic mastocytosis associated with myelodysplastic syndrome with the c-kit D816V mutation, which was refractory to imatinib treatment [44].
Interferon alpha also proved to be effective in the treatment of osteoporotic lesions appearing in the course of mastocytosis.
The series of 10 cases with resolved mastocytosis and osteoporosis-related fractures was presented in 2011. The patients received interferon alpha in a dose of 1.5 million units three times a week as well as pamindronic acid. The patients were treated for an average of 60 months. For the first 2 years, pamindronate was given at a dose of 1 mg/kg every month, and then every 3 months.
During the course of the study, no patient had a new-bone fracture. The level of alkaline phosphatase decreased by 25% in relation to the value before treatment and tryptase by 34%. Bone density increased during treated with interferon and pamindronate. The increase was on average 12% in the spine bones and 1.9% in the hip bones. At the same time, there was no increase in the density of the hip bone and a minimal increase in the density of the spine in patients treated with pamindronate alone.
The results of this observation suggest that it is beneficial to add low doses of interferon alpha to pamindronate treatment in terms of bone density increase [45].
That experiences show that interferon used in systemic mastocytosis significantly improves the quality of life of patients by inhibiting the symptoms caused by degranulation of mast cells. They prevent bone fractures and, in some patients, they cause remission of bone marrow infiltration by mast cells.
Chronic neutrophilic leukemia (CNL) is a very rare disease. It is characterized by the clonal proliferation of mature neutrophils.
The diagnostic criteria proposed by the World Health Organization (WHO) comprise leukocyte counts above 25,000/μl (including more than 80% of rod and segmented
Physical examination often shows enlargement of the liver and spleen, moreover, patients complain on weight loss and weakness [1].
The prognosis varies. The average survival time for patients with CNL is less than 2 years.
Only few descriptions of chronic neutrophilic leukemia are available in the literature, and these are mostly single case reports.
Because it is an extremely rare disease, there are no established and generally accepted treatment standards. In most cases, patients are given hydroxycarbamide or interferon. Patients who are eligible for a bone marrow transplant may benefit from this treatment. Bone marrow allotransplantation remains the only method that gives a chance for a significant extension of life.
The German authors presented a series of 14 cases of chronic neutrophilic leukemia. The group of patients consisted of eight women and six men. The average age was 64.7 years. From the entire group of patients, longer survival was achieved only in three cases. One of these patients was treated with interferon alpha and achieved hematological remission, the other underwent bone marrow allotransplantation from a family donor, and the third one was treated with hydroxycarbamide and transfusions as needed. The follow-up period of the patient after allogeneic matched related donor transplantation (allo-MRD) was 73 months, and for the patient after interferon treatment it was 41 months.
The remaining patients died within 2 years of diagnosis. Six patients, the largest group, died due to intracranial bleeding, three patients died because of leukemia cell tissue infiltration, one patient because of the disease transformation into leukemia, and one patient because of pneumonia [46].
It can be seen from these experiences that treatment with interferon alpha can significantly extend the survival time of patients.
The case of a 40-year-old woman diagnosed with chronic neutrophilic leukemia is presented by Yassin and coauthors. Initially, the patient had almost 41,000 leukocytes in the peripheral blood. In a physical examination, splenomegaly and hepatomegaly were not present. Patient received pegylated interferon alpha-2a. The initially dose was 50 μg once a week for the first 2 weeks, then the dose was increased to 135 μg weekly for 6 weeks, and then the dose interval was extended to another 2 weeks. As a result of the treatment, the general condition of the patient improved and the parameters of peripheral blood counts were normalized [47].
Another case report presented in the literature describes a 41-year-old woman diagnosed with CNL accompanied by focal segmental glomerulosclerosis (FSGS). The patient had increasing leukocytosis for several months. On the admission to the hospital, leukocytosis was 94,000/μl. Moreover, the number of platelets in the morphology exceeded 1,000,000/μl. More than a year earlier, the patient had splenectomy due to splenomegaly and spleen infraction.
Additionally, JAK2 V617F mutation was found. Some authors suggest that the presence of JAK2 mutation may be associated with longer survival in CNL.
The patient received hydroxycarbamide for 3 months and reduction in the number of leukocytes was achieved. After this time, interferon alpha-2b was added to hydroxycarbamide. As a result, focal segmental glomerulosclerosis disappeared and the renal tests improved [48].
Another case of chronic neutrophilic leukemia with a JAK2 gene mutation concerns a 53-year-old man. The patient’s baseline leukocytosis was 33,500/μl, including the neutrophil count of 29,700/μl. The patient also had splenomegaly.
The treatment with interferon alpha-2b at a dose of 3 million units every other day was started. After a month of treatment, the number of leukocytes was reduced to less than 10,000/μl. Then the patient was treated chronically with interferon alpha-2b in doses of 3 million units every 2 weeks. As a result of the therapy, the number of leukocytes remains between 8 and 10,000/μl. The patient remains in general good condition [49].
A series of two CNL cases are also shown. The first patient was a 70-year-old woman with stable leukocytosis of about 35,000/μl and the remaining morphology parameters in normal range. The patient was only observed for 5 years until hepasplenomegaly progressed rapidly. Then, interferon alpha-2b was included. Due to the treatment, the rapid regression of hepatosplenomegaly was achieved.
The second case is a 68-year-old woman with baseline leukocytosis of almost 14,000/μl. In this case, the treatment with hydroxycarbamide was started immediately. However, no improvement was achieved. After 6 weeks of HU treatment, interferon alpha-2b 3 million units 3 times a week was implemented and leukocytosis decreased. Due to the interferon treatment, the disease stabilized for a long time. Because the patient experienced an adverse reaction, a severe flu-like syndrome, interferon was discontinued. After interferon withdrawal, the disease progressed gradually and the treatment attempts by busulfan and 6-mercaptopurine were unsuccessful. Therefore, interferon was readministered and the disease went into remission. Interferon treatment was continued at a reduced dose. The disease regression was achieved again.
Additionally, the patient showed an improvement in the function of granulocytes in terms of phagocytosis and an improvement in neutral killer (NK) cell function after treatment with interferon [50].
The above examples show that interferon alpha is effective in the treatment of chronic neutrophilic leukemia. The side effects are rare and can be managed with dose reductions. Moreover, in these cases, interferon is also effective in a reduced dose. Disease remission or regression can be achieved without typical of CNL complications, such as intracranial bleeding.
Interferon has been used in the past to treat chronic myeloid leukemia. The treatment with tyrosine kinase inhibitors is now a standard practice. However, in a small number of patients, they are ineffective or exhibit unmanageable toxicity. Therefore, the attempts are underway to use interferon in combination with TKI in lower doses, which is to ensure the enhancement of the antiproliferative effect while reducing the toxicity.
There are ongoing attempts to use ropeginterferon in patients diagnosed with chronic myeloid leukemia, in whom treatment with imatinib alone has not led to deep molecular response (DMR). The first phase study was conducted in a small group of patients with chronic myeloid leukemia. The patients in first chronic phase treated with imatinib who did not achieve DMR, but in complete hematologic remission and complete cytogenetic remission, were included in the study. Patients have been treated with imatinib for at least 18 months. Twelve patients were enrolled in the study, and they completed the study according to the protocol. These patients received additional ropeginterferon to imatinib and four achieved DMR. Low toxicity was observed during the treatment. Among the hematological toxicities, neutropenia was the most common. There was no nonhematological toxicity with a degree higher than 1/2 during the treatment. Moreover, it has been found that better effects and fewer side effects are obtained when ropeginterferon is administered for a longer time, but in lower doses. The comparison of the effectiveness of interferon in chronic myeloproliferative disorders based on selected articles is presented in Table 1 [51].
Source | Type of trial | Interferon | Diagnosis | No. | Prior treatment status | Response rate |
---|---|---|---|---|---|---|
Yacoubet al. [15] | Phase II, multicenter | Pegylated IFN alfa-2a | PV | 50 | Resistance to HU or HU intolerance | CR:22% PR:38% |
ET | 65 | CR:43% PR:26% | ||||
Masarova et al. [16] | Phase II, single-center | Pegylated IFN alfa-2a | PV | 43 | Untreated or previously treated with cytoreductive therapy | CR:77% PR:7% |
ET | 40 | CR:73% PR:3% | ||||
Samuelsson et al. [18] | Phase II | Pegylated IFN alfa-2b | PV | 21 | Untreated or previously treated with cytoreductive therapy | CR: 69% for the entire group |
ET | 21 | |||||
Huang BT et al. [19] | Open label, multicenter | IFN alfa-2b | PV | 136 | Untreated or previously treated with cytoreductive therapy | OHR:70% Molecular response:54.7% |
ET | 123 | OHR (JAK2+ patients):83% CHR:23 cases OHR (JAK2-patients): 61.4% CHR:12 cases | ||||
Gisslinger et al. [23] | phase III, multicenter | Ropeginterferon | PV | 257 | Previously treated | OHR:53% |
Quintás-Cardama et al. [26] | phase II | Pegylated IFN alfa-2a | PV | 40 | Untreated or previously treated with cytoreductive therapy | OHR:80% CR:70% Molecular remission:54% |
ET | 39 | OHR:81% CR:76% Molecular remission:38% | ||||
Sørensen et al. [36] | Phase III, multicenter, COMBI | Pegylated IFN alfa-2a with ruxolitinib or Pegylated IFN alfa-2b with ruxolitinib | PV | 32 | Untreated or previously treated with cytoreductive therapy | OHR:44% CR:28% |
MF | 18 | OHR:31% CR:9% | ||||
Casassus et al. [40] | Open label, multicenter | IFN alpha-2b | Mastocytosis | 20 | Untreated and previously treated | PR:35% Minor remission: 30% |
Comparison of the effectiveness of interferon in chronic myeloproliferative disorders.
PV: polycythemia vera; ET: essential thrombocythemia; MF: myelofibrosis; HU: hydroxycarbamide/hydroxyurea; CR: complete remission; PR: partial remission; and OHR: overall hematological response.
Interferon alpha appears to be an effective and safe drug in the most type of chronic myeloproliferative disorders. Nowadays, all forms of its using have similar effectiveness. Interferon alpha can be effective even in cases of resistance for first-line treatment. Trial research is currently underway to combine it with some new drugs, such as ruxolitinib, and to add it to the already well-established therapy, it is a promising option for patients with refractory disease.
From time to time, new forms of interferon, such as ropeginterferon, are introduced, which gives hope for better effectiveness, better safety profile, and greater comfort in its use for patients who have to be treated for many years. In the case of the use of interferons alpha in the treatment of chronic myeloproliferative diseases, there are still opportunities to extend its use and to study its combination with newly introduced drugs.
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This chapter will be addressing the type of mycotoxins, its importance in food industry, preventive measures, and implementation of hazard analysis critical control point (HACCP) to control mycotoxin.",book:{id:"7913",slug:"mycotoxins-and-food-safety",title:"Mycotoxins and Food Safety",fullTitle:"Mycotoxins and Food Safety"},signatures:"Aycan Cinar and Elif Onbaşı",authors:[{id:"297267",title:"Ph.D.",name:"Aycan",middleName:null,surname:"Cinar",slug:"aycan-cinar",fullName:"Aycan Cinar"},{id:"297270",title:"MSc.",name:"Elif",middleName:null,surname:"Onbaşı",slug:"elif-onbasi",fullName:"Elif Onbaşı"}]},{id:"35124",doi:"10.5772/35353",title:"Principles and Methodologies for the Determination of Shelf-Life in Foods",slug:"principles-and-methodologies-for-the-determination-of-shelf-life-in-foods",totalDownloads:10919,totalCrossrefCites:13,totalDimensionsCites:25,abstract:null,book:{id:"1936",slug:"trends-in-vital-food-and-control-engineering",title:"Trends in Vital Food and Control Engineering",fullTitle:"Trends in Vital Food and Control Engineering"},signatures:"Antonio Valero, Elena Carrasco and Rosa Ma García-Gimeno",authors:[{id:"29379",title:"Dr.",name:"Elena",middleName:null,surname:"Carrasco",slug:"elena-carrasco",fullName:"Elena Carrasco"},{id:"35212",title:"Dr.",name:"Antonio",middleName:null,surname:"Valero",slug:"antonio-valero",fullName:"Antonio Valero"}]},{id:"27029",doi:"10.5772/29650",title:"Sensory Analysis of Virgin Olive Oil",slug:"the-sensory-analysis-of-virgin-olive-oil",totalDownloads:4850,totalCrossrefCites:7,totalDimensionsCites:25,abstract:null,book:{id:"869",slug:"olive-oil-constituents-quality-health-properties-and-bioconversions",title:"Olive Oil",fullTitle:"Olive Oil - Constituents, Quality, Health Properties and Bioconversions"},signatures:"Alessandra Bendini, Enrico Valli,Sara Barbieri and Tullia Gallina Toschi",authors:[{id:"78741",title:"PhD.",name:"Alessandra",middleName:null,surname:"Bendini",slug:"alessandra-bendini",fullName:"Alessandra Bendini"},{id:"78748",title:"Dr.",name:"Tullia",middleName:null,surname:"Gallina Toschi",slug:"tullia-gallina-toschi",fullName:"Tullia Gallina Toschi"},{id:"78750",title:"MSc.",name:"Sara",middleName:null,surname:"Barbieri",slug:"sara-barbieri",fullName:"Sara Barbieri"},{id:"78751",title:"MSc.",name:"Enrico",middleName:null,surname:"Valli",slug:"enrico-valli",fullName:"Enrico Valli"}]},{id:"27043",doi:"10.5772/30743",title:"Biological Properties of Hydroxytyrosol and Its Derivatives",slug:"biological-properties-of-hydroxytyrosol-and-its-derivatives",totalDownloads:8277,totalCrossrefCites:2,totalDimensionsCites:24,abstract:null,book:{id:"869",slug:"olive-oil-constituents-quality-health-properties-and-bioconversions",title:"Olive Oil",fullTitle:"Olive Oil - Constituents, Quality, Health Properties and Bioconversions"},signatures:"José G. Fernández-Bolaños, Óscar López, M. Ángeles López-García and Azucena Marset",authors:[{id:"84025",title:"Dr.",name:"José G.",middleName:null,surname:"Fernández-Bolaños",slug:"jose-g.-fernandez-bolanos",fullName:"José G. Fernández-Bolaños"},{id:"84258",title:"Dr.",name:"Óscar",middleName:null,surname:"López",slug:"oscar-lopez",fullName:"Óscar López"},{id:"84284",title:"MSc",name:"M. Ángeles",middleName:null,surname:"López-García",slug:"m.-angeles-lopez-garcia",fullName:"M. Ángeles López-García"},{id:"84287",title:"MSc.",name:"Azucena",middleName:null,surname:"Marset",slug:"azucena-marset",fullName:"Azucena Marset"}]}],mostDownloadedChaptersLast30Days:[{id:"71718",title:"Understanding Africa’s Food Security Challenges",slug:"understanding-africa-s-food-security-challenges",totalDownloads:1629,totalCrossrefCites:6,totalDimensionsCites:11,abstract:"Africa, sub-Saharan Africa (SSA) in particular, has for more than 10 years recorded a steady economic growth since the advent of the new millennium. Yet, despite this stellar economic growth, it faces challenges such as rapid population growth, persistent economic inequality, climate change threats, droughts, youth unemployment, undernourishment, and food insecurity. Understanding the state of food security in Africa, and addressing the above-mentioned challenges, should be the highest priority for Africa’s Political Leadership. Not doing so will forever make Africa fail to achieve a sustainable economic development and create an inclusive shared-prosperity for its people. The African Union (AU), as well as respective national governments and regional organizations, and the international community at large, have in recent decades launched a multitude of policy initiatives aimed at addressing and tackling Africa’s food insecurity and nutrition challenges. Despite those efforts and commitments by the disparate stakeholders, much remains to be done. This chapter presents Africa’s food security and nutrition challenges, and sheds light on the climate change threats and potential consequences of the rapid population growth on Africa’s food security. The chapter concludes with policy recommendations and proposals and makes points about Africa’s bright prospects if food security were to be achieved.",book:{id:"8063",slug:"food-security-in-africa",title:"Food Security in Africa",fullTitle:"Food Security in Africa"},signatures:"Mahamat Kabirou Dodo",authors:[{id:"301440",title:"Ph.D.",name:"Mahamat Kabirou",middleName:null,surname:"Dodo",slug:"mahamat-kabirou-dodo",fullName:"Mahamat Kabirou Dodo"}]},{id:"69691",title:"Food Contamination",slug:"food-contamination",totalDownloads:1072,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"This chapter discusses food contamination including mycotoxin contamination problems, biological, chemical, physical, and cross contamination. Food contamination challenges are generally referred to the presence of microorganisms or derived toxic substances such as mycotoxin in food that make them unsafe for human, animals, and crops. The mycotoxins can enter food throughout the food supply chain (from farm to fork). In terms of the safety of food, the presence of mycotoxin is a hazard threatening the consumer of contaminated food. Furthermore, it is necessary to know the nature, sources, distribution ways, and incidence of mycotoxin contamination in order to protect people and provide public health.",book:{id:"7913",slug:"mycotoxins-and-food-safety",title:"Mycotoxins and Food Safety",fullTitle:"Mycotoxins and Food Safety"},signatures:"Anna Abdolshahi and Behdad Shokrollahi Yancheshmeh",authors:[{id:"295585",title:"Dr.",name:"Anna",middleName:null,surname:"Abdolshahi",slug:"anna-abdolshahi",fullName:"Anna Abdolshahi"},{id:"297628",title:"Dr.",name:"Behdad",middleName:null,surname:"Shokrollahi Yancheshmeh",slug:"behdad-shokrollahi-yancheshmeh",fullName:"Behdad Shokrollahi Yancheshmeh"}]},{id:"72086",title:"The Role of Small-Scale Farmers in Ensuring Food Security in Africa",slug:"the-role-of-small-scale-farmers-in-ensuring-food-security-in-africa",totalDownloads:1234,totalCrossrefCites:3,totalDimensionsCites:4,abstract:"This chapter focuses on the role of African small-scale farmers in ensuring food security going into the future and the support they will need to face the projected climatic conditions. Severe climatic conditions contribute to the uncertainty in water availability for future agricultural production. Adapting to climate change and ensuring food security requires dynamic interventions that will lead to the transformation of current farming and food production patterns as well as food distribution. Nearly 95% of Africa’s agriculture is rainfed; therefore, developing and promoting rain-fed small-scale agricultural activities is a cost-effective approach for transforming rural areas in Africa and ensuring food security at local and regional levels. This is crucial in reducing vulnerability to climate change and for building sustainable livelihoods.",book:{id:"8063",slug:"food-security-in-africa",title:"Food Security in Africa",fullTitle:"Food Security in Africa"},signatures:"Samkelisiwe Nosipho Hlophe-Ginindza and N.S. Mpandeli",authors:[{id:"301810",title:"Dr.",name:"Samkelisiwe Nosipho",middleName:null,surname:"Hlophe-Ginindza",slug:"samkelisiwe-nosipho-hlophe-ginindza",fullName:"Samkelisiwe Nosipho Hlophe-Ginindza"},{id:"308051",title:"Prof.",name:"N.S.",middleName:null,surname:"Mpandeli",slug:"n.s.-mpandeli",fullName:"N.S. Mpandeli"}]},{id:"27042",title:"Oleocanthal: A Naturally Occurring Anti-Inflammatory Agent in Virgin Olive Oil",slug:"oleocanthal-a-naturally-occurring-anti-inflammatory-agent-in-virgin-olive-oil",totalDownloads:7261,totalCrossrefCites:5,totalDimensionsCites:22,abstract:null,book:{id:"869",slug:"olive-oil-constituents-quality-health-properties-and-bioconversions",title:"Olive Oil",fullTitle:"Olive Oil - Constituents, Quality, Health Properties and Bioconversions"},signatures:"S. Cicerale, L. J. Lucas and R. S. J. Keast",authors:[{id:"75123",title:"Prof.",name:"Russell",middleName:null,surname:"Keast",slug:"russell-keast",fullName:"Russell Keast"}]},{id:"69163",title:"Mycotoxins: The Hidden Danger in Foods",slug:"mycotoxins-the-hidden-danger-in-foods",totalDownloads:2302,totalCrossrefCites:12,totalDimensionsCites:30,abstract:"Mycotoxins are secondary metabolites synthesized by a variety of fungal species such as Aspergillus, Penicillium, Fusarium, and Alternaria. These secondary metabolites are toxic and have a significant impact if they enter the production and food chain. Mycotoxins have attracted worldwide attention because of their impact on human health, huge economic losses, and domestic and foreign trade. Although more than 400 mycotoxins have been identified, most studies have focused on aflatoxins (AF), ochratoxin A (OTA), Fusarium toxins, fumonisin (FUM), zearalenone (ZEA), trichothecenes (TCT), and deoxynivalenol/nivalenol due to food safety and economic losses. This chapter will be addressing the type of mycotoxins, its importance in food industry, preventive measures, and implementation of hazard analysis critical control point (HACCP) to control mycotoxin.",book:{id:"7913",slug:"mycotoxins-and-food-safety",title:"Mycotoxins and Food Safety",fullTitle:"Mycotoxins and Food Safety"},signatures:"Aycan Cinar and Elif Onbaşı",authors:[{id:"297267",title:"Ph.D.",name:"Aycan",middleName:null,surname:"Cinar",slug:"aycan-cinar",fullName:"Aycan Cinar"},{id:"297270",title:"MSc.",name:"Elif",middleName:null,surname:"Onbaşı",slug:"elif-onbasi",fullName:"Elif Onbaşı"}]}],onlineFirstChaptersFilter:{topicId:"327",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81786",title:"Mycotoxins … Silent Death",slug:"mycotoxins-silent-death",totalDownloads:6,totalDimensionsCites:0,doi:"10.5772/intechopen.104382",abstract:"There are many types of fungi that produce secondary metabolites called mycotoxins. These compounds are very dangerous to humans and animals, as exposure to them causes acute or chronic toxicity. Temperature, humidity and pH are important environmental factors in the production of mycotoxins. There are about 500 types of mycotoxins that are found in many agricultural products such as peanut, cereals, wines, fruit juice, dried fruits, feed, and other foodstuffs. Among the most important genera of fungi that produce mycotoxins are Aspergillus, Penicillium, Altenaria, Fusarium, and others. Some of them infect plants in the field and produce mycotoxin, while others infect agricultural crops, foodstuffs, and feed in the store and produce mycotoxin during storage conditions. Mycotoxins are divided into various groups according to the degree of their impact and danger, into highly toxic, low toxic, carcinogenic, and mutagenic. This is depends on the chemical composition of the different types of mycotoxins, which are an open hydrocarbon chain with low molecular weights ranging between 100 and 697 Da. The biological effects of mycotoxins include damage to living tissues, suppression of immunity, and neurological disorders. Aflatoxins are one of the most dangerous mycotoxins as they are the main cause of hepatocellular carcinoma and the fifth most common carcinogen in the world.",book:{id:"11023",title:"Mycotoxins and Food Safety - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11023.jpg"},signatures:"Azhar A. Alhaddad"},{id:"81871",title:"The Influence of Some Contaminants in Food Quality",slug:"the-influence-of-some-contaminants-in-food-quality",totalDownloads:12,totalDimensionsCites:0,doi:"10.5772/intechopen.102911",abstract:"The concept of food quality has been following scientific and technological evolution. Currently, producers, users, consumers, as well as public authorities, have well defined their expectations regarding the quality requirements in the food sector. These projections are related to several parameters that are no longer seen only from a safety and nutritional point of view. Thus, the characteristics of food products must fulfill criteria that embrace their origin, esthetics, convenience, functionality, ethics, organoleptic and must result in benefit. The needs of consumers increasingly reflect public interests, which are supervised by public authorities that hold technical and scientific information that allows them to advocate normative regulations regarding defects, adulteration, and fraud, increasing awareness in the food quality field. Since food quality and safety are two increasingly interconnected domains, the different EU legislation and regulations impose procedures for the determination of contaminants. In this chapter, we will only cover three main topics, namely heavy metals, polycyclic aromatic hydrocarbons, and mycotoxins.",book:{id:"11023",title:"Mycotoxins and Food Safety - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11023.jpg"},signatures:"Marisa Nicolai, Paula Pereira and Lídia Palma"},{id:"80942",title:"Mycotoxin Decontamination of Foods Using Nonthermal Plasma and Plasma-Activated Water",slug:"mycotoxin-decontamination-of-foods-using-nonthermal-plasma-and-plasma-activated-water",totalDownloads:55,totalDimensionsCites:1,doi:"10.5772/intechopen.103779",abstract:"Mycotoxins are food safety and public health concerns due to their widespread contamination in agricultural products and adverse health effects on humans. Several decontamination techniques, including physical-, chemical-, and thermal-based treatments, are employed to minimize the levels of mycotoxins in food. However, these treatments present disadvantages, such as negative impacts on the quality and leftover chemical residues on the treated food after physical- and chemical-based treatments. Furthermore, mycotoxins are resistant to heat, thus contributing to the insufficiency of thermal treatments for complete mycotoxin degradation. The use of alternative nonthermal-based treatments, such as nonthermal plasma (NTP) and plasma-activated water (PAW) for mycotoxin degradation in food, have been recently explored to overcome these limitations. NTP and PAW treatments are known to minimize the unfavorable changes in food quality while ensuring safety from food contaminants. The basics of NTP and PAW technologies, their mycotoxin decontamination efficiencies, their underlying mechanisms of action, effects on food quality, and the safety of mycotoxin degradation byproducts and treated food are hereby discussed in this chapter.",book:{id:"11023",title:"Mycotoxins and Food Safety - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11023.jpg"},signatures:"Hsiu-Ling Chen, Rachelle D. Arcega, Samuel Herianto, Chih-Yao Hou and Chia-Min Lin"},{id:"80268",title:"Animal Feeds Mycotoxins and Risk Management",slug:"animal-feeds-mycotoxins-and-risk-management",totalDownloads:76,totalDimensionsCites:0,doi:"10.5772/intechopen.102010",abstract:"The demand for livestock products is the main factor affecting the demand for livestock feeds worldwide. However, animal feed safety has gradually become more important, with mycotoxins representing one of the most significant hazards. Mycotoxins are toxic secondary metabolites produced naturally by fungi that grow on various agriculture commodities. Aflatoxin, fumonisin, ochratoxin, trichothecene, and zearalenone are the more prevalent mycotoxins in animal feeds. Some of mycotoxins impacts include; loss of animal and human health, reduced animal productivity, increased veterinary service costs, feed disposal and increased research costs which enhance the importance of mycotoxins detoxification. Contamination of feeds may occur both during pre-harvest and post-harvest. The purpose of this chapter is to review the most prevalent mycotoxins in animal feeds, reveal the origin of mycotoxins contamination and the possible risks they pose to feeds and livestock. This chapter also gives an overview of the most important factors that influence mold growth and mycotoxin production as well as the economic impacts of mycotoxins. To the end of this chapter, mycotoxins preventive methods, both preharvest and postharvest, are well discussed.",book:{id:"11023",title:"Mycotoxins and Food Safety - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11023.jpg"},signatures:"Zacharia Waithaka Ng’ang’a and Eric Niyonshuti"},{id:"80725",title:"Implications of Mycotoxins in Food Safety",slug:"implications-of-mycotoxins-in-food-safety",totalDownloads:78,totalDimensionsCites:0,doi:"10.5772/intechopen.102495",abstract:"The chapter aims to address an overview of the implications of mycotoxins in food safety and the presence of mycotoxins in various foods. Nowadays, everyone wants safe food with a long shelf life. Food safety has become a major strategic issue worldwide and has attracted worldwide attention. Mycotoxins are widely found in food and feed, and dietary exposure to them can induce various types of adverse health effects in humans and animals. Contamination of food by fungi and mycotoxins results in loss of dry matter, quality and nutrition, and poses a significant danger to the food chain. Moreover, mycotoxin contamination decreases product quality and reduces export values, which can lead to significant economic losses for producing countries. Mycotoxin contamination directly reduces food availability and has its own contribution to hunger and malnutrition, and the consumption of food contaminated with mycotoxins has major repercussions on human health.",book:{id:"11023",title:"Mycotoxins and Food Safety - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11023.jpg"},signatures:"Romina Alina Marc"},{id:"79582",title:"Cunninghamella bertholletiae’s Toxins from Decomposing Cassava: Mitigation Strategy for Toxin Reduction Using Nepenthes mirabilis ‘Monkey Cup’ Digestive Fluids",slug:"cunninghamella-bertholletiae-s-toxins-from-decomposing-cassava-mitigation-strategy-for-toxin-reducti",totalDownloads:94,totalDimensionsCites:0,doi:"10.5772/intechopen.101353",abstract:"A fermentation technique was utilised to assess a fungus, i.e. Cunninghamella bertholletiae/polymorpha, isolated from rotting cassava, ability to produce mycotoxins and resultant oxidation by-products of the mycotoxins using liquid chromatography–mass spectrometry (LC/MS). Thus, the mycotoxins/secondary metabolites, fumonisin B1 (FB1) and deoxynivalenol (DON) were produced while, heptadecanone, octadecanamide, octadecenal and 3-keto-deoxynivalenol (DON) were successfully identified as biodegradation by-products in the fermentation broth treated with hydrolysing ‘monkey cup’ juice from Nepenthes mirabilis. Exposure to the mycotoxins and the biodegradation by-products through consumption of contaminated produce including contact due to the cumulative presence in arable agricultural soil can be harmful to humans and animals. Therefore, this work reports on a strategy for the mitigation and reduction of mycotoxins in agricultural soil using natural plant pitcher juices from N. mirabilis’ ‘monkey cup’.",book:{id:"11023",title:"Mycotoxins and Food Safety - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11023.jpg"},signatures:"Elie Fereche Itoba-Tombo, Seteno Karabo Obed Ntwampe, John Baptist Nzukizi Mudumbi, Lukhanyo Mekuto, Enoch Akinbiyi Akinpelu and Nkosikho Dlangamandla"}],onlineFirstChaptersTotal:7},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:141,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:124,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"August 2nd, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:33,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. 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He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. 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He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. 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Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. 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She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. 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He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:{name:"Association for Computing Machinery",country:{name:"United States of America"}}},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. 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:"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:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{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:"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:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"426586",title:"Dr.",name:"Oladunni A.",middleName:null,surname:"Daramola",slug:"oladunni-a.-daramola",fullName:"Oladunni A. Daramola",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Federal University of Technology",country:{name:"Nigeria"}}},{id:"357014",title:"Prof.",name:"Leon",middleName:null,surname:"Bobrowski",slug:"leon-bobrowski",fullName:"Leon Bobrowski",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Bialystok University of Technology",country:{name:"Poland"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"354126",title:"Dr.",name:"Setiawan",middleName:null,surname:"Hadi",slug:"setiawan-hadi",fullName:"Setiawan Hadi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Padjadjaran University",country:{name:"Indonesia"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"332603",title:"Prof.",name:"Kumar S.",middleName:null,surname:"Ray",slug:"kumar-s.-ray",fullName:"Kumar S. Ray",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Statistical Institute",country:{name:"India"}}},{id:"415409",title:"Prof.",name:"Maghsoud",middleName:null,surname:"Amiri",slug:"maghsoud-amiri",fullName:"Maghsoud Amiri",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Allameh Tabataba'i University",country:{name:"Iran"}}},{id:"357085",title:"Mr.",name:"P. Mohan",middleName:null,surname:"Anand",slug:"p.-mohan-anand",fullName:"P. Mohan Anand",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356696",title:"Ph.D. Student",name:"P.V.",middleName:null,surname:"Sai Charan",slug:"p.v.-sai-charan",fullName:"P.V. Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}}]}},subseries:{item:{id:"1",type:"subseries",title:"Oral Health",keywords:"Oral Health, Dental Care, Diagnosis, Diagnostic Imaging, Early Diagnosis, Oral Cancer, Conservative Treatment, Epidemiology, Comprehensive Dental Care, Complementary Therapies, Holistic Health",scope:"
\r\n\tThis topic aims to provide a comprehensive overview of the latest trends in Oral Health based on recent scientific evidence. Subjects will include an overview of oral diseases and infections, systemic diseases affecting the oral cavity, prevention, diagnosis, treatment, epidemiology, as well as current clinical recommendations for the management of oral, dental, and periodontal diseases.
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Her qualifications are: a specialist in Dental Imaging and Radiology, Master in Dentistry (Periodontics) from the University of São Paulo (FORP-USP, Ribeirão Preto, SP), and Doctor (Ph.D.) in Dentistry (Stomatology Clinic) from Hospital São Lucas of the Pontifical Catholic University of Rio Grande do Sul (HSL-PUCRS, Porto Alegre, RS). She held a postdoctoral internship at the Federal University from Jequitinhonha and Mucuri Valleys (UFVJM, Diamantina, MG). She is currently a member of the Brazilian Society for Dental Research (SBPqO) and the Brazilian Society of Stomatology and Pathology (SOBEP). Dr. Marinho's experience in Dentistry mainly covers the following subjects: oral diagnosis, oral radiology; oral medicine; lesions and oral infections; oral pathology, laser therapy and epidemiological studies.",institutionString:null,institution:{name:"State University of Paraíba",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,series:{id:"3",title:"Dentistry",doi:"10.5772/intechopen.71199",issn:"2631-6218"},editorialBoard:[{id:"267724",title:"Prof.",name:"Febronia",middleName:null,surname:"Kahabuka",slug:"febronia-kahabuka",fullName:"Febronia Kahabuka",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZpJQAW/Profile_Picture_2022-06-27T12:00:42.JPG",institutionString:"Muhimbili University of Health and Allied Sciences, Tanzania",institution:{name:"Muhimbili University of Health and Allied Sciences",institutionURL:null,country:{name:"Tanzania"}}},{id:"70530",title:"Dr.",name:"Márcio",middleName:"Campos",surname:"Oliveira",slug:"marcio-oliveira",fullName:"Márcio Oliveira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRm0AQAS/Profile_Picture_2022-08-01T12:34:46.jpg",institutionString:null,institution:{name:"State University of Feira de Santana",institutionURL:null,country:{name:"Brazil"}}}]},onlineFirstChapters:{paginationCount:2,paginationItems:[{id:"82936",title:"Soil Degradation Processes Linked to Long-Term Forest-Type Damage",doi:"10.5772/intechopen.106390",signatures:"Pavel Samec, Aleš Kučera and Gabriela Tomášová",slug:"soil-degradation-processes-linked-to-long-term-forest-type-damage",totalDownloads:3,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Forest Degradation Under Global Change",coverURL:"https://cdn.intechopen.com/books/images_new/11457.jpg",subseries:{id:"94",title:"Climate Change and Environmental Sustainability"}}},{id:"82124",title:"Assessment of Diversity, Growth Characteristics and Aboveground Biomass of Tree Species in Selected Urban Green Areas of Osogbo, Osun State",doi:"10.5772/intechopen.104982",signatures:"Omolara Aremu, Olusola O. 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Currently, he is a professor of Orthodontics. He holds a Certificate of Advanced Study type A in Technology of Biomaterials used in Dentistry (1995); Certificate of Advanced Study type B in Dento-Facial Orthopaedics (1997) from the Faculty of Dental Surgery, University Denis Diderot-Paris VII, France; Diploma of Advanced Study (DESA) in Biocompatibility of Biomaterials from the Faculty of Medicine and Pharmacy of Casablanca (2002); Certificate of Clinical Occlusodontics from the Faculty of Dentistry of Casablanca (2004); University Diploma of Biostatistics and Perceptual Health Measurement from the Faculty of Medicine and Pharmacy of Casablanca (2011); and a University Diploma of Pedagogy of Odontological Sciences from the Faculty of Dentistry of Casablanca (2013). 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