IAH classification based on IAP value [5].
\r\n\t
",isbn:null,printIsbn:null,pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"a26ccbc19aca1adeac18323671b48289",bookSignature:"Dr. Gunvant Birajdar",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/8387.jpg",keywords:"Finite Difference Method, Fractional PDEs, Laplace Transform method, Fourier Transform Method, Katugampola , Hilfer-Katugampola Derivatives, Hilfer Derivatives, Fractional Differential Operator, History of Fractional Calculus, Different Fractional Operators",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 8th 2018",dateEndSecondStepPublish:"November 29th 2018",dateEndThirdStepPublish:"January 28th 2019",dateEndFourthStepPublish:"April 18th 2019",dateEndFifthStepPublish:"June 17th 2019",remainingDaysToSecondStep:"2 years",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"191049",title:"Dr.",name:"Gunvant",middleName:null,surname:"Birajdar",slug:"gunvant-birajdar",fullName:"Gunvant Birajdar",profilePictureURL:"https://mts.intechopen.com/storage/users/191049/images/system/191049.jpeg",biography:"Dr. Birajdar earned a Ph.D. in Mathematics from Department of Mathematics, Dr. Babasaheb Ambedkar\nMarathwada University, Aurangabad (M.S.) with a PhD thesis On Numerical Techniques in Nonlinear Fractional Partial Differential Equations and Applications. He is presently performing the role of a Assistant Professor at Tata Institute of Social Sciences (TISS), Tuljapur, Maharashtra since July 2013.",institutionString:"Tata institute of Social Sciences",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Tata Institute of Social Sciences",institutionURL:null,country:{name:"India"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"15",title:"Mathematics",slug:"mathematics"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"205697",firstName:"Kristina",lastName:"Kardum Cvitan",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/205697/images/5186_n.jpg",email:"kristina.k@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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It is grown on about 219 million hectares all over the world (Figure 1) and is the basic staple food of mankind, providing humans with 18% of their daily intake of calories and 20% of their protein (http://faostat.fao.org/). The wheat-growing area within the Mediterranean Basin represents 27% of the arable land (Figure 2), and the region represents 60% of the world’s growing area for durum wheat, the species used for pasta manufacturing. The Mediterranean dietary traditions have often been related to health benefits and the prevention of cardiovascular disease [1]. The Mediterranean diet is the heritage of millennia of exchanges between people, cultures and foods of all countries around the Mediterranean Basin, and during the twentieth century, it has been the basis of food habits in all countries of the region, originally based on Mediterranean agricultural and rural models [2]. Cereals, and mostly wheat in the form of bread, pasta or couscous, form the base of the pyramid and are daily included as part of the main meals [3].
\nGlobal wheat distribution. Each point represents 20,000 t of grain production (modified from CIMMYT).
Total wheat harvested area and wheat production in coastal countries to the Mediterranean Sea from 1961 until 2014 (own elaboration from FAOSTAT data;
There are several species of the wheat genus (
Wheat was one of the first domesticated food crops and its history is that of humanity. The domestication of wheat and the beginning of agriculture go hand in hand. Kislev [4] classified the data of wheat husbandry into three major phases: (
The crucial separation of individuals of the
The first signs of cultivation of the so-called emmer (an awned wild wheat) correspond to the Pre-Pottery Neolithic A period (10,300–9500 BP), at the end of which all basic agricultural practices had already been established [6]. The transformation of some wild cultivated forms into domesticated wheats proceeded very rapidly from this stage. From the Karacadaĝ Mountains, emmer spread first northward and then southward. There is a general agreement that domestication occurred at the beginning of the Pre-Pottery Neolithic B (9500–7500 BP) [7, 12], when the spontaneous crosses between grasses that led to the appearance of bread wheat probably took place. Plant domestication was driven by humans’ need to secure the greatest possible amount of food with the least possible labour.
\nWheat domestication involved major morphological, physiological and adaptive changes in plants, most of them induced by humans. One of the clearest examples of the contribution of humans to domestication was the transformation of the spike axis from brittle to tough. In wheat ancestors, the spike became brittle at maturity, falling apart into small pieces (spikelets) containing the seeds, which were spread by wind and animals as an essential mechanism of propagation and survival. However, a small number of plants (those carrying a recessive allele conferring axis robustness) tended to develop robust spike axes, and this caused the seeds to remain together in the spike at ripeness without falling down. This feature was very beneficial for humans, as it allowed them to harvest complete spikes at ripening instead of unripe spikes. It is likely that seed collectors gradually increased the proportion of tough-axis spikes gathered, thus unconsciously favouring the tough-axis genes in the harvested grains, which led to a suppression of the brittle axis in domesticated wheats [13]. Thus, due to the loss of the seed-dispersal mechanism, wheat started to depend on humans for survival. Other important changes that occurred during domestication were the reduction of grain self-protection (due to the loss of the leaf-like glumes that covered each seed), which made the grains free-threshing, and the loss of seed dormancy, which favoured a uniform and rapid seed germination.
\nThe establishment of agriculture in the Levant and the neighbouring regions was a very gradual evolutionary process that took place over a period of several hundred years [7, 12]. Studies conducted today to imitate different harvest techniques of wild wheats grown in a dense stand suggest that at that time, it was possible to obtain about 0.5–1 kg of pure grain per hour or 300–700 kg of grain per hectare or even more [14, 15]. This significant improvement led to a substantial population growth.
\nIn the Ceramic or Pottery Neolithic, the wheat culture spreads from the western flank of the Fertile Crescent to southeast Europe through Transcaucasia, reaching the Balkan Peninsula and Greece in about 8000 years BP. Primitive wheat was transported by ships along the coast of the Mediterranean Sea to Italy and Spain (7000 BP) [5, 16] and south of Gibraltar. Two possible ways have been proposed for the introduction of durum wheat into the Iberian Peninsula: North Africa and south-eastern Europe [6, 17]. Wheat reached Egypt through Israel and Jordan [5].
\nAfter arriving in a given territory, wheat underwent a progressive adaptation to the varying conditions of the new area and gradually established new strategies for yield formation, which likely conferred adaptive advantages under the new environmental conditions [18]. During the dispersal of wheat along the Mediterranean Basin, the farmers took their habits wherever they went, not just sowing, reaping and threshing but also other well-established technologies such as baking and fermenting. This process of migration and natural and human selection resulted in the establishment of a wide diversity of local landraces specifically adapted to different agro-ecological zones. These dynamic populations with distinct identities are considered to be genetically more diverse than currently cultivated varieties (Figure 3); they show local adaptation and are associated with traditional farming systems [19].
\nVariability in spike morphology in durum wheat Mediterranean landraces.
The Mediterranean Basin comprises countries between 27° and 47°N and between 10°W and 37°E, including three continents with a coastline of 46,000 km. In this region, wheat is grown in a range of environmental conditions varying from favourable to dry land areas. In the Mediterranean climate, most rain falls in autumn and winter, and a water deficit appears in spring, resulting in moderate stress for wheat around anthesis that increases in severity throughout the grain-filling period. However, the climatic conditions of the north and the south of the Mediterranean Basin have great differences. While the north has temperate and cold climates (classes C and D, respectively, according to the Koppen climate classification), the south has a dry climate (class B according to the same classification) [20]. Scientific evidence has shown that contrasting adaptation strategies occurred during the spread of wheat over the north (via Turkey, Greece and Italy) and south (via North Africa) of the Mediterranean Basin. The different climates prevalent in the zones of adaptation may have induced gradual changes in crop phenology and in the strategies used by wheat to form its yield during its dispersal from the east to the west of the Mediterranean Basin [21]. Royo et al. [18] demonstrated that the number of days to heading and flowering of traditional durum wheat varieties (landraces) increased from the warmest and driest zone of the Mediterranean Basin to the coldest and wettest one. Durum wheat landraces collected in the north of the Mediterranean Basin have been found to have more stems per unit area, more biomass, a higher proportion of biomass and leaf area allocated on tillers at flowering and heavier grains than those collected in the south [18, 21, 22]. African landraces of diploid, tetraploid and hexaploid wheats have been reported to carry genes for tolerance to physical environmental stresses [23] and are therefore better adapted to drought environments than those of northern countries [22]. Durum wheat landraces from southern Mediterranean countries allocate more biomass to the main stem, produce more grains per spike and per unit area and have higher harvest index than those from northern countries [21, 22]. These differences mean that grain yield of landraces collected in northern Mediterranean countries is mainly related to variations in grain weight, whereas grain yield of landraces collected in the drier and warmer southern countries is mainly related to the number of spikes per unit area [21].
\nDuring the first few decades of the twentieth century, the wheat varieties grown in the Mediterranean were the so-called traditional varieties or landraces. Landraces resulted jointly from the evolution of wheat during its dispersal to new territories and from the role of humans in selecting large spikes for planting the next generation after the advent of agriculture. Landraces are heterogeneous in their shape because they are populations formed by sets of plants with different genetic constitutions. Their huge genetic diversity makes them a particularly important group of genetic resources. Knowledge of the genetic diversity and population structure of landraces is essential for their conservation and efficient use in breeding programmes. The first diversity studies used phenotypic markers of morphological and physiological traits, but DNA-based markers are currently extensively used as they are not affected by the environment and can be detected in all tissues at all developmental stages. Among them, microsatellites or simple sequence repeats (SSRs) have proven to be very useful for evaluating the genetic diversity and population structure of Mediterranean wheat collections [17, 24–29].
\nA number of studies have been conducted by our team to assess the genetic diversity and population structure of Mediterranean durum wheat germplasm. In all cases, the genetic structure of the landrace populations proved to be associated with the geographical origin of accessions. The study of Moragues et al. [17], which used a set of 63 durum wheat landraces from 12 Mediterranean countries, grouped the accessions in two clusters: (
A recent study by Soriano et al. [29] classified a collection of 152 durum wheat landraces and old varieties from 21 Mediterranean countries into four subpopulations that showed an eastern-western geographical pattern (Figure 4): eastern Mediterranean, eastern Balkans and Turkey, western Balkans and Egypt and western Mediterranean. The genetic diversity found by Soriano et al. [29] was lower in the eastern Mediterranean group, indicating that the diversity of wheat increased during the dispersal from its area of domestication to the western Mediterranean Basin.
\nGenetic structure of the Mediterranean durum wheat landraces and old varieties reported by Soriano et al. [
A study was carried out by Ruiz et al. [26] on a collection of 190 durum wheat Spanish landraces. The results showed that the diversity and agro-morphological traits were correlated with geographic and climatic features. The distribution of the collection in nine clusters was largely determined by the three subspecies,
During the last century, a large number of wheat germplasm accessions have been collected by Mediterranean gene banks. Western Mediterranean countries (Portugal, Spain, southern France, Morocco, Algeria and Tunisia) have been identified as one of the principal regions for collecting tetraploid wheats due to the variability gathered by local germplasm [23]. As the management of the whole collections is costly and inefficient, if the collection shows a significant level of redundancy, core collections consisting of a limited set of accessions that maximize the genetic variation contained in the whole collection with a minimum of repetitiveness [30] have been created. The bread wheat worldwide core collection formed by Balfourier et al. [31] from 3942 cultivars included 372 accessions, 149 of which came from 18 countries around the Mediterranean Basin. The accessions were grouped using molecular markers according to their geographical distribution—western and southern Europe, the eastern Mediterranean Basin, North Africa, Turkey, the Balkans and finally France—which was grouped with cultivars from central and northern European countries. The Spanish durum wheat core collection created by Ruiz et al. [26] includes 94 accessions representative of a collection of 555 Spanish landraces and old cultivars and contains a wide range of genotypes adapted to Mediterranean environments.
\nMediterranean landraces have a good adaptation to Mediterranean environments. They can be considered as likely sources of putatively lost variability and may provide favourable alleles for the improvement of commercially valuable traits, especially in breeding for suboptimal environments. However, their plant height, general lateness and low harvest index limit the attainment of high yields, particularly when they are grown in intensive agricultural systems. A study by our team conducted on 154 durum landraces from 20 Mediterranean countries revealed that landraces from western Mediterranean countries had greater grain-filling rates and heavier grains than those of eastern ones [32]. The contribution of landraces in wheat breeding programmes also seems possible in terms of end-product quality, given the high level of polymorphism of key quality genes and the large genetic diversity found for quality traits between and within landrace populations [33–35]. It has been reported that specific Mediterranean durum wheat landraces may be used as sources of quality improvement for grain protein content, gluten strength, grain weight, test weight and general quality [32]. In order to identify durum wheat landraces as potential parents in breeding programmes for gluten strength enhancement, Nazco et al. [35, 36] analysed the allelic composition at five glutenin loci on a collection of 155 durum wheat landraces and old varieties from 21 Mediterranean countries and 18 representative modern cultivars. The results indicated that landraces with outstanding gluten strength were more frequent in eastern than in western Mediterranean countries. Only 9 different allelic combinations were identified in modern cultivars, but 126 in the landraces, 3 of them new with a positive effect on gluten strength [36]. Twelve banding patterns positively affecting gluten strength were identified in the landraces [35].
\nThe pioneer breeders or entrepreneurial Mediterranean agriculturalists started selecting from within landrace populations (sometimes from foreign countries) the plants with the most favourable characteristics in terms of vigour, phenological adaptation, spike length and yield in order to produce superior lines. This pure-line selection did not entail the development of new genotypes as the improvement was only achieved by identifying and isolating the best lines already existing within the original landrace. This methodology was used by Nazareno Strampelli in Italy to release the durum wheat cultivar ‘Senatore Cappelli’ in 1915 from the Algerian population ‘Jean Retifah’ [37], by Enrique Sánchez-Monge Parellada in Spain to release the barley variety ‘Albacete’ from a selection within a local population, the bread wheat ‘Aragón 03’ selected by Manuel Gadea from a selection within the local variety ‘Catalán de Monte’ and the durum wheat varieties ‘Andalucía 344’ and ‘Jerez 36’ obtained in Spain by Juan Bautista Camacho from ‘Manchón de Alcalá la Real’ and ‘Raspinegro de Alcolea’, respectively [38].
\nThe first organized wheat programme in France was implemented by the Vilmorin family in the eighteenth century [39]. When Mendel’s laws were rediscovered at the beginning of the twentieth century plant breeding was established as a science, making crosses between varieties or breeding lines selected in the previous phase of breeding. The Italian breeder Nazareno Strampelli, considered the local promotor of the Mendelian findings, started to make crosses around 1900 [40]. In parallel, breeders started to interchange germplasm and to use foreign varieties or lines developed by their colleagues in other countries, for crossing with their best types. Farmer breeding was also encouraged by the collection and distribution of wheat seed from all over the world. In the 1850s, the harvest index (the partitioning of photosynthates between the grain and the vegetative plant) of most wheats was about 0.3 or less [41].
\nFrom around 1940, breeding programmes based on scientific findings were created in a number of countries. One of the most famous was the Rockefeller-Mexico programme, led by Dr. Norman Borlaug, which started in 1945, which used germplasm from different origins in his crosses. The particularities of Mexico allowed Borlaug’s programme to grow two cropping seasons every year, thus speeding the breeding process. Using Norin 10, a Japanese variety, and the cross Norin/Brevor as a parental, Borlaug obtained ‘semi-dwarf wheats’ that yielded far better than the taller wheats grown in most parts of the world at that time. The incorporation of the dwarfing genes designated as
Field plots of a durum wheat landrace (left) and a semi-dwarf improved variety (right).
The semi-dwarf varieties developed in Mexico were rapidly adopted by Mediterranean countries, leading to the progressive abandonment of the cultivation of landraces. The adoption of improved semi-dwarf varieties was accompanied by the intensification of management practices to allow the semi-dwarf wheats to express their potentiality. The progress achieved for grain yield until 1982 was the result of combining improved varieties with appropriate crop management strategies. Sowing densities, application of fertilizers (particularly nitrogen), irrigation and the use of pesticides to control weeds and diseases increased resulting in yield rises in many countries. International Maize and Wheat Improvement Center (CIMMYT) was formally launched in 1966, and Norman Borlaug was honoured with the Nobel Peace prize in 1970 for his contribution to the Green Revolution.
\nAdvances in yield during the twentieth century in Mediterranean countries due to variety improvement have been widely reported in the literature for bread wheat [43–45] and durum wheat ([42, 46] and references therein). The role played by the variety is generally ascertained by growing historical series of cultivars in a common environment. Following this approach, our group quantified yield increases during the last century in 35.1 kg ha−1 y−1, or 0.88% y−1 in relative terms, for bread wheat in Spain [43] and in 16.9 and 23.6 kg ha−1 y−1 (0.51 and 0.72% y−1 in relative terms) for durum wheat in Italy and Spain, respectively [47]. For both species, the modification of plant architecture by the introduction of dwarfing alleles played a major role in the achieved gains [42, 43], by reducing plant height and reallocating photosynthates in reproductive organs of plants with more grains per spike and improved tillering capacity [42, 43]. In Spain, changes of harvest index during the twentieth century have been estimated by our team to be from 0.25 to 0.40 in bread wheat [44] and from 0.36 to 0.44 in durum wheat [42, 48]. However, the GA insensitivity conferred by the dwarfing genes
The effect of dwarfism was greater on the root system than on aerial biomass, reducing the aerial biomass of each plant at anthesis by 7.6% and the root by 28.1% [49]. However, despite their reduced root biomass, modern cultivars are more responsive in terms of yield and number of grains per spike to environments with high water input after anthesis [50]. Breeding also improved adaptation to Mediterranean conditions by reducing cycle length to flowering [44, 51], thus benefiting grain setting [46] and improving photosynthesis during grain filling [44] in environments characterized by terminal stresses. The adaptation pattern of bread wheat changed towards varieties with a wider adaptation to variable environmental conditions and spring types that performed better than landraces in environments with high temperatures before heading [52]. However, our results also evidenced a slowdown in bread wheat yield increases since 1970 [43]. Breeding activities improved the overall processing quality of wheat for making bread and pasta. Although most modern cultivars have less grain protein content than traditional varieties, breeding activities during the twentieth century in Mediterranean countries resulted in an improvement of global grain quality in both bread and durum wheat [44, 53].
\nComprehensive information about the history of wheat breeding in Mediterranean countries may be found in Bonjean et al. [39, 54] and Royo et al. [55].
\nAlthough the Green Revolution was critical for raising wheat production enough to mitigate the effect of rapid demographic growth, it affected the natural habitat of wheat. Landraces and pure-line cultivars obtained through mass selection from them during the first decades of the twentieth century were widely grown until the late 1960s, but due to the massive introduction of the homogeneous and more productive semi-dwarf cultivars released since the Green Revolution, they practically disappeared from farmer’s fields. Particularly, in the domestication area of wheat and the Mediterranean regions, which are the reservoir of the greatest genetic variability of the species, wild relatives and landraces were displaced by improved varieties. In consequence, the variability present on farmer fields due to the cultivation of old unimproved varieties (landraces) gave way to the genetic uniformity of the most productive modern cultivars. The decrease in cultivar diversity and the loss of the natural variation present in landraces increased the genetic vulnerability of wheat crops [23] and led to a loss of the diversity exploitable by plant breeders, the so-called genetic erosion. Among the factors that have been reported to contribute to the narrow genetic background underlying successful modern wheat varieties, the reduced number of ancestors and the relatively small number of varieties cultivated at present are among the most significant [56, 57].
\nAnother important change derived from the advent of modern cereal culture was the requirement of field uniformity, which led to the planting of large extensions of a single variety or a small number of varieties, managed under similar cultural practices. This homogeneity is very convenient from the industrial and commercial viewpoints as it allows sets of tons of wheat grains with similar quality characteristics to be obtained. However, it most likely increases the vulnerability to diseases as the pressure exerted by large extensions of uniform varieties pushes the races of fungal species to mutate, and to very rapidly overcome the genetic resistance of cultivars [58].
\nSeveral global and regional climate models suggest that the Mediterranean Basin might be an especially vulnerable region to global change [59]. A pronounced decrease in precipitation and warming are projected, particularly in the summer season, with large interannual variability leading to a greater occurrence of extremely high-temperature events [59, 60]. The impact of agricultural practices on climate change has redesigned the breeding paradigm. While past yield improvements relied on the development of improved varieties that needed the intensification of agricultural practices to maximize yields, the new released varieties have to be able to produce with the minimum environmental impact, that is, they must fit into the concept of ‘sustainable agricultural ecosystems’. This entails their genetic adaptation to environmental conditions, making it unnecessary to modify the environment through the use of non-sustainable practices to cover the variety requirements, as was the case in the past. This is a huge challenge for breeders, as wheat breeding today largely depends on the incorporation in improved varieties of adaptive traits for specific environments.
\nGiven that most traits useful for improving the adaptation of modern cultivars to abiotic or biotic constraints cannot be found in modern cultivars, in many cases the enlargement of the genetic variability has to be sought in local landraces and close-related species. The high genetic diversity of landraces buffers them against spatial and temporal variability and upgrades the resilience to abiotic and biotic stresses in comparison with modern varieties [61, 62]. The essential role of landraces as likely sources of highly beneficial untapped diversity has led them to be considered essential for food security because they are potential providers of new favourable genes to be incorporated into modern cultivars. However, as the genetic variation contained in them is usually unknown, the effective use of landraces in breeding programmes will make necessary to evaluate the existing diversity in the gene pool and to characterize the available accessions [62]. Detecting the presence of variants of potential interest for breeding purposes in landraces may be particularly useful in situations of breeding for suboptimal environments.
\nAmong the set of wheat landraces, the ones coming from the Mediterranean Basin are considered to hold the largest genetic variability within the species as shown by the genetic variability found in Portuguese [63] and Spanish [34] wheats. Mediterranean wheat landraces are considered as a potential genetic resource of drought resistance, frost tolerance and biotic and abiotic stresses in general. In addition, as mentioned above, an increase in the available genetic variation through the use of landraces in breeding programmes seems possible in terms of yield component enhancement and end-product quality.
\nThe enormously expanding potential of recently developed technologies offers opportunities for improvement of plant traits and agricultural management that were inconceivable few decades ago. Genomics offers new opportunities to dissect traits of quantitative inheritance and chromosomal regions whose allelic variation may be statistically associated with a specific trait. During the last few decades, several types of molecular markers have been used for wheat genetic studies, providing effective genotyping but resulting costly and time-consuming due to the low number of markers to be screened in a single reaction. In the last few years, the advances in next-generation sequencing (NGS) technologies has reduced the costs of DNA sequencing to the point that genotyping based on sequence data is now feasible for high-diversity and large-genome species. New high-throughput platforms have been developed in bread wheat, such as single nucleotide polymorphism (SNP) arrays [64, 65] and genotyping by sequencing (GBS) platforms, e.g., DArT-seq, developed by Diversity Arrays Technology Pty Ltd (Canberra, Australia). In early 2017 the bread wheat genome sequence was released providing wheat researchers with a new resource to identify the most influential genes that are important to wheat adaptation, stress response, pest resistance and improved yield. Recent scientific breakthroughs in genome-editing technologies, such as the clustered regularly interspaced short palindromic repeat (CRISPR), have opened new avenues for accelerating basic research and plant breeding by providing the means to modify genomes rapidly in a precise and predictable manner [66]. With recent biotechnology developments, advances in statistics, precision agriculture and information technologies such as geographic information system (GIS), remote sensing and the exploitation of big data among other new tools will hopefully help to meet the challenges of breeders and agronomists in the next few decades.
\nThe authors thank INIA, MINECO (projects AGL2012-37217 and AGL2015-65351-R) and IRTA for supporting wheat research programmes in Spain. JM Soriano is employed by the INIA-DOC program funded by the European Social Fund with the contribution of the CERCA Programme (Generalitat de Catalunya).
\nA progressive increase in intra-abdominal pressure initially results in intra-abdominal hypertension and later, affects end-organ perfusion resulting in abdominal compartment syndrome. It is often under-diagnosed as the end-organ perfusion caused by intra-abdominal hypertension in this patient population can also be explained by their overall critical condition. Thus, clinicians must have a high suspicion for intra-abdominal hypertension to prevent it from progressing to compartment syndrome and death.
The abdomen is a closed cavity with a steady state pressure within it. This pressure is called Intra-abdominal pressure (IAP). Intra-abdominal pressure depends on the abdominal wall compliance and volume of the organs within the abdominal cavity. Thus, it is affected by the conditions that decreases the compliance of the wall (burn eschars or third spacing) or by additional volume of organs (such as fecal matter, presence of ascites, or space-occupying lesions such as tumors) [1].
Normal IAP varies between 5–7 mmHg [2]. Body Mass Index positively affects IAP with pressure being high in pregnant and morbidly obese individuals. Similarly, recent abdominal surgery can also affect the IAP.
Abdominal perfusion pressure (APP) is measured by subtraction of intra-abdominal pressure from the mean arterial pressure (MAP) [3].
With the increase in IAP, APP decreases, and thereby, causing decreased perfusion to the abdominal viscera. APP is a better maker than arterial pH, base deficit, arterial lactate and hourly urine output, as an endpoint for resuscitation.
The World Society of Abdominal Compartment Syndrome (WSACS) established the definition of IAH and ACS in 2004 [4].Intra-abdominal hypertension (IAH) is defined as intra-abdominal pressure (IAP) greater than or equal to 12 mmHg.
IAH is further graded based on the IAP as shown in Table 1.
Grades | IAP |
---|---|
Grade I | 12–15 mmHg |
Grade II | 16–20 mmHg |
Grade III | 21–25 mmHg |
Grade IV | >25 mmHg |
IAH classification based on IAP value [5].
IAH can also be divided as follows based on duration:
Hyperacute IAH refers to the transient elevation of the intra-abdominal pressure lasting for seconds such as while laughing, sneezing, straining, coughing.
Acute IAH refers to the sustained elevation of IAP over hours such as in intra-abdominal trauma or hemorrhage and has the potential to progress to ACS.
Subacute IAH refers to the elevation of IAP over days and is mostly seen in the MICU patients receiving large volume resuscitation and also has potential to progress to ACS.
Chronic IAH refers to the elevation of IAP over months to years such as in patients with increased abdominal wall compliance (pregnant or morbidly obese). These patients are at high risk for development of ACS if they have superimposed acute or subacute IAH [6].
Oliguria is most often the first sign of IAH. FG is measured as glomerular filtration pressure (GFP) – PTP (proximal tubular pressure) and is a measure of pressure across the glomerulus.
Since,
Therefore,
Thus,
This equation shows that changes in IAP have a higher effect on renal function and urine production than changes in MAP [7].
Abdominal compartment syndrome (ACS) is defined as sustained IAP above 20 mmHg with evidence of end-organ dysfunction. ACS is further classified into primary, secondary, and recurrent based on the etiology and duration of end-organ failure.
Primary: ACS occurring due to etiology primarily within the abdominopelvic cavity is termed as primary; for example, abdominal trauma, pancreatitis, abdominal surgery, hemoperitoneum, liver transplantation. It frequently requires early surgical or interventional radiology intervention [8].
Secondary: ACS occurring due to extra-abdominal etiology; example: fluid resuscitation, sepsis, burns.
Recurrent: Development of ACS again after the early resolution of the previous either primary or secondary ACS. It can occur despite the presence of an open abdomen or after abdominal closure following the resolution of the first episode. It is associated with significant morbidity and mortality [9].
Abdominal compartment syndrome has been studied widely in surgical and trauma patients. However, very few studies are available on the MICU patients. Many patients in MICU undergo large-volume resuscitation common conditions such as sepsis, hemorrhage, systemic inflammatory response syndrome, and are at high risk for the development of IAH. An incidence study done on MICU patients receiving large-volume resuscitation showed that 85% of patients enrolled developed IAH with IAP > 12 mmHg, 33% developed IAP > 20 mmHg and 25% met the criteria for ACS. These patients had median fluid balance of +6.9 L and Acute Physiology and Chronic Health Evaluation II (APACHE II) score of 23. Thus, data emphasized the high incidence of IAH in MICU patients receiving large-volume resuscitation [10]. In another prospective multi-institutional study done in 15 ICUs, of 491 patients enrolled, IAH occurred in almost half of all the patients and was twice as common in mechanically ventilated patients compared to those who were breathing spontaneously The study revealed that intra-abdominal hypertension proportionally increased the 28 and 90-day mortality [11]. Given the prevalence of IAH/ACS and associated mortality, it is important to be vigilant regarding the ACS development in MICU, especially in patients receiving the large-volume resuscitation.
The abdomen is a closed cavity surrounded by rigid (pelvic bones, rib cage, spine) and flexible borders (Visceral organs, abdominal wall, diaphragm). There is an extent to which abdominal girth can increase and after an extent, the girth does not increase and results in intra-abdominal hypertension and thus, progressing to abdominal compartment syndrome.
Risk factors for IAH and ACS development can be divided as follows Table 2:
Risk factors for IAH and ACS |
1. Decrease in abdominal wall compliance Burn Eschars Rectus sheath hematoma Obesity (BMI > 30 kg/m2) Ascites Abdominal surgery Mechanical ventilation with high PEEP Prone positioning |
2. Increase in intra-abdominal volume Fecal matter/air/fluid within the organs Intestinal/Gastric distention such as colonic pseudo-obstruction, ileus, gastroparesis Damage control laparotomy Retroperitoneal tumor or hemorrhage Pancreatitis Abdominal abscess Hemo/Pneumoperitoneum Liver transplantation Peritoneal dialysis Peritonitis |
3. Secondary ACS Large volume resuscitation (> 5 L fluids in 24 hours) Hypothermia (core temperature less than 33 degree Celsius) Acidosis (pH < 7.2) Massive blood transfusion (>10 PRBC in 24 hrs) Coagulopathy (platelets <55,000 or prothrombin time > 15 secs or INR >1.5) Sepsis Major burns |
Risk factors predisposing to IAH and ACS [12].
Like any other compartment syndrome, an increase in IAH, causes the decrease in perfusion of the contents within the abdominal cavity due to increased venous resistance, causing decreased capillary perfusion. However, IAH is an area of particular significance given the multi-systemic effect involving cardiac, pulmonary, and renal systems. Patients with underlying cardiomyopathy, renal insufficiency, pulmonary diseases are at high risk of decompensation [13].
Increase in IAP causes cephalad movement of the diaphragm leading to increased intrathoracic pressure. This phenomenon results in the following:
Decrease venous return: Increase in IAP, increases the pressure in the IVC and with the cephalad motion of the diaphragm, the thoracic inlet of the IVC constricts; thus, decreasing the venous return and the preload, thereby, affecting a component of cardiac output. Decreased venous return increases the hydrostatic pressure in lower extremities resulting in peripheral edema and increased risk for development of deep vein thrombosis [14].
Increase SVR: Increase in IAP causes increased pressure in systemic and aortic vasculature and also, increase pulmonary vascular resistance secondary to increased intrathoracic pressure. These factors thus increase SVR and thereby, decreasing the cardiac output [15].
Impaired cardiac function: Elevation of the diaphragm and increased intrathoracic pressure caused by IAH also causes cardiac compression, thus, decreasing ventricular compliance and contractility.
In conclusion, the MAP is affected by both SVR and Cardiac output. In absence of severe IAH, SVR increases, and cardiac output decreases (due to decreased preload). Thus, MAP remains stable despite a decrease in both preload and cardiac output. However, in patients with decreased intravascular volume or with poor cardiac function, even a mild to moderate increase in IAP can result in decreasing MAP. Therefore, preload augmentation with volume resuscitation appears to be beneficial to compensate for the increasing systemic vascular resistance. In ventilated patients, high PEEP or auto-PEEP can further decrease the venous return and thus, are also at risk of decompensation at the lower elevation of IAP.
An increase in the IAP compresses the lung parenchyma by direct transmission of IAP and cephalad deviation of the diaphragm. Compression of lung parenchyma thus results in atelectasis, which results in increasing shunting of the blood and causes ventilation-perfusion mismatch. The atelectatic lung is also at higher risk for infection. In mechanically ventilated patients, increased IAP causes the peak inspiratory pressure and mean airway pressure to increase, thus causing the alveolar barotrauma. These patients also have decreased chest wall compliance and spontaneous tidal volume, causing hypoxemia and hypercarbia, which are the clinical features of ACS [16].
IAH significantly decreases the renal function and thus urine output by significantly affecting the renal blood flow. In comparison with superior mesenteric and celiac blood flow, studies have shown preferential decrease in renal blood flow with elevated IAP [17]. IAH results in renal arterial constriction and an increase in renal venous resistance, thus causing decrease in the venous drainage from the kidney. Secondarily, a decrease in cardiac output also results in activation of the renin-angiotensin-aldosterone system, thus causing renal arterial vasoconstriction. As mentioned above an increase in IAP affects the filtration gradient and thus, resulting in a net decrease in urine output. A study has shown development of oliguria at IAP of approximately 15 mmHg, whereas elevation of IAP to 30 mmHg results in anuria [18].
The gut is most sensitive to increased IAP. It affects the gut in the following ways:
Decreasing mesenteric blood flow: Mesenteric blood flow is decreased at IAP as low as 10 mmHg. A study showed 43% decrease in the celiac artery blood flow and 69% decrease in superior mesenteric artery blood flow when IAP is elevated to 40 mmHg. This is accentuated by shock and hypotension [17].
Compressing mesenteric veins: IAH compresses mesenteric veins in the intestinal wall causing impaired venous flow from the intestine and thus, causing intestinal edema. This edema in turn causes an elevation in the IAP, thus initiating a vicious cycle. This results in worsened hypoperfusion leading to elevation of lactic acid and intestinal ischemia.
Loss of intestinal mucosa: Gut hypoperfusion results in the loss of protective intestinal mucosal barrier, leading to gut bacterial translocation and results, in sepsis with multi-organ failure [19].
Elevation in IAP causes decreased hepatic arterial flow and increases the portal venous and hepatic venous resistance, thus, resulting in decreased microcirculatory blood flow in the liver. This results in decreased mitochondrial function and production of ATPs. Overall, the liver’s capacity to clear lactic acid decreases. This has been seen at IAP elevation to as low as 10 mmHg in presence of normal cardiac output and MAP [20].
Elevation in IAP causes increase in intracranial pressure (ICP) by decreasing the lumbar venous plexus blood flow and decreasing the cerebral venous outflow. Overall increase in partial pressure of carbon dioxide results in cerebral venous constriction resulting in increased ICP This, in turn, decreases the cerebral perfusion pressure and function [21].
Increased IAP can cause a decrease in blood flow to the abdominal wall, leading to wall ischemia and edema. Rectus sheath blood flow decreases in proportion to increase in the intra-abdominal pressure. It decreases by approximately 58% from baseline with IAP as low as 10 mmHg. This further reduces the abdominal wall compliance and exacerbates the IAH [22].
Early identification of IAH is imperative to prevent further progression to ACS. Most patients with ACS are critically ill and unable to express the symptoms, therefore, identifying the signs of IAH or developing ACS is very important.
Intraabdominal hypertension through its delirious effect on multi-organ system including kidney, lungs and cardiovascular system results in following clinical entities as mentioned in Table 3 [23]. These clinical signs are seen commonly in critically ill patients having multiple comorbidities. Thus, it is very important to measure IAP at early stage and have high suspicion for ACS.
Signs of ACS |
|
Clinical signs of abdominal compartment syndrome [23].
These are not diagnostic for ACS, however, can be used as signs for early identification for developing abdominal compartment syndrome. Chest X-ray significant for elevated hemidiaphragm, pulmonary atelectasis and decreased lung volumes. CT scan findings are consistent with abdominal distention, tense infiltration of retroperitoneum out of proportion to the retroperitoneal disease, extrinsic compression of IVC or renal displacement, bowel wall thickening [24].
In multiple prospective studies, the sensitivity of clinical examination in the diagnosis of IAH is only 40–60% [25, 26]. Abdomen being a hollow cavity filled with viscera, IAP can be measured by measuring the pressure within various viscera. However, IAP is typically measured via trans-bladder pressure measurement as recommended by the World Society of Abdominal Compartment Syndrome (WSACS) in 2006 due to ease of measurement [27]. Other ways to measure IAP include manometry from the abdominal drain, measuring pressure from central venous catheter inserted into inferior vena cava, measuring pressure via nasogastric tube, measuring rectal/uterine pressure [28]. Advanced modalities such as measuring abdominal wall thickness via ultrasound are also currently being investigated.
Measurement of intravesical pressure has evolved over the years to decrease complications including the need for repeat measurements, urinary tract infection, and to decrease the incidence of needlestick injuries. The most common technique used is as follows:
A three-way stopcock is used to decrease the number of times an aspiration port is accessed.
A saline infusion set with 1000 ml normal saline bag is inserted in the first stopcock.
A 50 ml syringe is attached to the 2nd stopcock.
The third stopcock is attached to the pressure transducer and it is zeroed at a point where the mid-axillary line crosses the iliac crest.
The urine drainage port of the foley is clamped.
Instill 25 ml normal saline at room temperature into the bladder. Given that this normal saline can also result in detrusor muscle contraction and falsely increased the measured IAP, it is advisable to wait 30–60 seconds after saline administration to measure the pressure. Also, the patient should be in the complete supine position with a measurement done at end-expiration to ensure no abdominal muscle contraction is present. The measurement is done after the stopcocks to the pressure transducer is opened.
Although, intravesical pressure measurement is the gold standard to measure the intra-abdominal pressure, it has many technical difficulties. Though the evolution of technique has decreased the risk of needlestick injuries, this technique still is cumbersome, intermittent and carries potential risk of urinary tract infection. Most of the ventilated patients in MICU have head of bed elevated to prevent aspiration risk and studies have shown that the intravesical pressure increases significantly even with mild head of bed elevation [29].
This method involves measurement of the pressure within the stomach using the nasogastric tube. It can be used when the patient does not have a foley catheter or intravesical pressure measurement is not possible due to bladder trauma, pelvic hematoma, peritoneal adhesions or neurogenic bladder. The use of tonometer to measure the intragastric pressure has been validated and showed good correlation with the IAP [30]. However, the IAP measured via nasogastric tube is affected by the migrating motor complex and the effects of enteral tube feeding on the IAP measurement are still unknown. The intra-gastric pressure measurement can also be used to monitor continuous intra-abdominal pressure. The most advanced method involves the air-pouch system where the tip of the nasogastric tube contains a pressure transducer which can automatically calibrate every hour and provides continuous intra-abdominal pressure measurement, however, this method is not validated in humans yet.
IVC catheter placed via femoral cannulation can be connected to the pressure transducer to provide IVC pressure measurement. A study validating the indirect methods of IAP measurement in rabbits showed good correlation of IVC and transvesical pressure with direct intraperitoneal pressure measurements. However, IVC catheter are associated with increased risk of infection and sepsis. A multicenter observational study showed that femoral vein pressure has good correlation with the IAP when intra-abdominal pressure is >20 mmHg and can be used as a surrogate to bladder pressure, thus, allowing continuous measurement of IAP [31].
Rectal and transvaginal pressure measurement is less practical given the pressure can be affected by the residual fecal mass or gynecological bleeding. Both these techniques have not been validated in the ICU setting [32].
Management of ACS involves early recognition of IAH and/or end-organ failure and prompt interventions. It has been outlined by WSACS as shown in Figures 1 and 2. Management can be divided into medical and surgical interventions.
Medical management for intra-abdominal hypertension [
Evaluation and management of abdominal compartment syndrome [
Non-surgical measures include decreasing the IAP by decreasing the content within the visceral organs that might be causing the IAH. Ileus is a common post-abdominal surgical complication and is also common amongst patients receiving large volume resuscitation, in patients with peritonitis, electrolyte imbalance and those receiving narcotic medications. These factors are independently associated to increase risk for IAH/ACS. Thus, treating ileus by nasogastric suction and rectal suction, use of prokinetic agents, colonoscopic decompression, and frequent enemas helps to decrease IAP by decreasing the volume of intra-luminal contents.
In patients where extra-luminal factors are leading to elevated IAH, alleviating the cause is most advisable to improve the abdominal wall compliance. If any space-occupying lesion is contributing to the IAH, thorough investigation including Ultrasound and CT scan should be done to identify the nature of space occupying lesion (SOL) and if indicated, either percutaneous drainage or surgical removal of the SOL can help with reducing the IAP. If ascites is contributing to the IAH, then therapeutic paracentesis can help. However, in patients with progressive IAH or not responding to therapeutic paracentesis, continuous percutaneous drainage guided by Ultrasound or CT scan should be considered. Studies have shown that continuous percutaneous drainage decreases the rate of open abdominal decompression in 81% of the patients treated. However, if percutaneous drain fails to drain at least 1 L of fluid and decrease the intra-abdominal pressure by at least 9 mmHg in first four hours, the likelihood for requirement of surgical decompression increases [33].
Abdominal compliance can also be improved by adequate sedation and analgesia, removal of constrictive dressing, and eschars. Supine positioning or reverse Trendelenburg position also helps alleviate the abdominal muscle contracture. Low evidence is available but neuromuscular blockade should be considered per WSACS guidelines [27].
Managing the volume status of the patient is equally important, as hypovolemia can further exacerbate the effects of IAH and the large volume resuscitation can also similarly be shown as a predictive factor for progression to ACS. Thus, it’s important to judge the volume status of the patient and maintain euvolemia. Hemodynamic monitoring is advisable for judicious administration of fluids. Recent study in burn patients receiving large volume resuscitation has shown that hypertonic saline or colloid solution effectively decreases the risk for developing IAH/ACS [34].
Despite adequate fluid resuscitation, some patients with IAH/ACS develop total body fluid overload secondary to capillary leakage and excessive third spacing with significant elevation in IAP [35]. Diuretics are generally contraindicated as these patients are intravascularly volume depleted. However, once these patients become hemodynamically stable with resolution of shock, diuretics along with colloid administration helps to the fluid from the third space. Continuous renal replacement therapy to remove excess fluid judiciously and increase abdominal wall compliance can also help decrease the IAP However, it’s important to ensure that intra-vascular volume is adequately maintained for appropriate organ perfusion and avoidance of multi-organ failure development secondary to inadequate perfusion.
When the non-surgical methods fail to consistently decrease the IAP, surgical abdominal decompression via laparotomy is the treatment of choice. Decompressive laparotomy results in a decrease in intra-abdominal volume and thus decreases the IAP. Delay in surgical depression in surgical and non-surgical patients is associated with increased mortality [36]. There is also an increased risk of ischemia–reperfusion syndrome especially in patients with significantly high IAP for a prolonged period. Abdominal laparotomy with negative peritoneal pressure therapy is preferred given that it improves visceral perfusion and also decreases bacterial translocation. In multiple studies, surgical decompression has been shown to decrease IAP and improve respiratory, cardiac, and renal function [37]. However, studies on the mortality related to ACS requiring decompressive laparotomy are inconclusive as there is a significant difference in when the decision to do decompression is made by the intensivist based on their specialty. Studies have shown that medical intensivists prefer diuresis and dialysis more and take double the time than surgical intensivists to decide on decompressive laparotomy. Surgical decompression, though a life-saving procedure, has significant morbidity and mortality associated with it. In a study, three out of four patients of severe acute pancreatitis who underwent surgical decompression died and two of them from uncontrollable retroperitoneal hemorrhage [38].
Decompressive laparotomy can result in excess loss of fluids from the exposed tissue resulting in exsanguination or can result in a large ventral hernia or fistula [39]. The open abdomen also increases risk for bacterial translocation and sepsis. Thus, steps should be taken to close the abdomen as soon as possible with most surgeons planning staged closure every 48 hours. Continued manometric measurement of IAP even after abdominal closure is necessary.
ACS is associated with high mortality and hence, it’s imperative to identify the early signs of intra-abdominal hypertension. Presence of IAH on day 1 of ICU is not an independent risk factor for mortality, however, occurrence and persistence of IAH during the ICU stay has significant associated with mortality [40]. Studies have shown that mortality increases proportionally with abdominal hypertension. A study showed 45.1% mortality in ACS patients compared to 21% mortality in patients with increased IAP [41]. Most common cause leading to death includes sepsis and multi-organ failure.
Intra-abdominal hypertension and abdominal compartment syndrome are prevalent amongst critically ill medical patients and associated with high mortality. Thus, medical staff should have a high suspicion of ACS in critically ill patients. Large volume resuscitation should be rationalized, and early surgical decompression must be considered if indicated.
The authors declare no conflict of interest.
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\\n\\nEntire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by, or on behalf of, the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (known as the "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of any fraudulent pre-contract misrepresentation or concealment.
\\n\\nWaiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\\n\\nVariation: No variation of this Publication Agreement shall have effect unless it is in writing and signed by the parties, or their duly authorized representatives.
\\n\\nSeverance: If any provision, or part-provision, of this Publication Agreement is, or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted. Any modification to, or deletion of, a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\\n\\nNo partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Author or any Co-Author, nor authorize any party to make or enter into any commitments for, or on behalf of, any other party.
\\n\\nGoverning law: This Publication Agreement and any dispute or claim, including non-contractual disputes or claims arising out of, or in connection with it, or its subject matter or formation, shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of, or in connection with, this Publication Agreement, including any non-contractual disputes or claims.
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\\n"}]'},components:[{type:"htmlEditorComponent",content:'When submitting a manuscript, the Author is required to accept the Terms and Conditions set out in our Publication Agreement – Monographs/Compacts as follows:
\n\nCORRESPONDING AUTHOR'S GRANT OF RIGHTS
\n\nSubject to the following Article, the Author grants to IntechOpen, during the full term of copyright, and any extensions or renewals of that term, the following:
\n\nThe foregoing licenses shall survive the expiry or termination of this Publication Agreement for any reason.
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\n\nSubject to the license granted above, copyright in the Work and all versions of it created during IntechOpen's editing process, including all published versions, is retained by the Author and any Co-Authors.
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\n\nAll rights granted to IntechOpen in this Article are assignable, sublicensable or otherwise transferrable to third parties without the specific approval of the Author or Co-Authors.
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\n\nAUTHOR'S DUTIES
\n\nWhen distributing or re-publishing the Work, the Author agrees to credit the Monograph/Compacts as the source of first publication, as well as IntechOpen. The Author guarantees that Co-Authors will also credit the Monograph/Compacts as the source of first publication, as well as IntechOpen, when they are distributing or re-publishing the Work.
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\n\nThe Author will be held responsible for the payment of the agreed Open Access Publishing Fee before the completion of the project (Monograph/Compacts publication).
\n\nAll payments shall be due 30 days from the date of issue of the invoice. The Author or whoever is paying on behalf of the Author and Co-Authors will bear all banking and similar charges incurred.
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\n\nThe Author shall obtain written informed consent for publication from those who might recognize themselves or be identified by others, for example from case reports or photographs.
\n\nThe Author shall respect confidentiality during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Author and Co-Authors are confidential and are intended only for the recipients. The contents of any communication may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
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\n\nThe Author and Co-Authors also confirm and warrant that: (i) he/she has the power to enter into this Publication Agreement on his or her own behalf and on behalf of each Co-Author; and (ii) has the necessary rights and/or title in and to the Work to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licences in this Publication Agreement. If the Work was prepared jointly by the Author and Co-Authors, the Author confirms that: (i) all Co-Authors agree to the submission, license and publication of the Work on the terms of this Publication Agreement; and (ii) the Author has the authority to enter into this biding Publication Agreement on behalf of each Co-Author. The Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each Co-Author.
\n\nThe Author agrees to indemnify IntechOpen harmless against all liabilities, costs, expenses, damages and losses, as well as all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of, or in connection with, any breach of the agreed confirmations and warranties. This indemnity shall not apply in a situation in which a claim results from IntechOpen's negligence or willful misconduct.
\n\nNothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\n\nTERMINATION
\n\nIntechOpen has the right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Author and/or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Author and/or any Co-Author (being a private individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Author and/or any Co-Author (as a corporate entity) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for, or enters into, any compromise or arrangement with any of its creditors.
\n\nIn the event of termination, IntechOpen will notify the Author of the decision in writing.
\n\nIntechOpen’s DUTIES AND RIGHTS
\n\nUnless prevented from doing so by events beyond its reasonable control, IntechOpen, at its discretion, agrees to publish the Work attributing it to the Author and Co-Authors.
\n\nUnless prevented from doing so by events beyond its reasonable control, IntechOpen agrees to provide publishing services which include: managing editing (editorial and publishing process coordination, Author assistance); publishing software technology; language copyediting; typesetting; online publishing; hosting and web management; and abstracting and indexing services.
\n\nIntechOpen agrees to offer free online access to readers and use reasonable efforts to promote the Publication to relevant audiences.
\n\nIntechOpen is granted the authority to enforce the rights from this Publication Agreement on behalf of the Author and Co-Authors against third parties, for example in cases of plagiarism or copyright infringements. In respect of any such infringement or suspected infringement of the copyright in the Work, IntechOpen shall have absolute discretion in addressing any such infringement that is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\n\nIntechOpen has the right to include/use the Author and Co-Authors names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Work and has the right to contact the Author and Co-Authors until the Work is publicly available on any platform owned and/or operated by IntechOpen.
\n\nMISCELLANEOUS
\n\nFurther Assurance: The Author shall ensure that any relevant third party, including any Co-Author, shall execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\n\nThird Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\n\nEntire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by, or on behalf of, the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (known as the "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of any fraudulent pre-contract misrepresentation or concealment.
\n\nWaiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\n\nVariation: No variation of this Publication Agreement shall have effect unless it is in writing and signed by the parties, or their duly authorized representatives.
\n\nSeverance: If any provision, or part-provision, of this Publication Agreement is, or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted. Any modification to, or deletion of, a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\n\nNo partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Author or any Co-Author, nor authorize any party to make or enter into any commitments for, or on behalf of, any other party.
\n\nGoverning law: This Publication Agreement and any dispute or claim, including non-contractual disputes or claims arising out of, or in connection with it, or its subject matter or formation, shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of, or in connection with, this Publication Agreement, including any non-contractual disputes or claims.
\n\nPolicy last updated: 2018-09-11
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