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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
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Their characteristic features are the intuitive graphical modeling language and advanced formal analysis method. The concurrence of performed actions is the natural phenomenon due to which Petri Nets are perceived as mathematical tool for modeling concurrent systems. The nets whose model was extended with the time model can be applied in modeling real-time systems.\r\n\r\nPetri Nets were introduced in the doctoral dissertation by K.A. Petri, titled “„Kommunikation mit Automaten” and published in 1962 by University of Bonn. During more than 40 years of development of this theory, many different classes were formed and the scope of applications was extended. Depending on particular needs, the net definition was changed and adjusted to the considered problem. The unusual “flexibility” of this theory makes it possible to introduce all these modifications. Owing to varied currently known net classes, it is relatively easy to find a proper class for the specific application. The present monograph shows the whole spectrum of Petri Nets applications, from classic applications (to which the theory is specially dedicated) like computer science and control systems, through fault diagnosis, manufacturing, power systems, traffic systems, transport and down to Web applications. At the same time, the publication describes the diversity of investigations performed with use of Petri Nets in science centers all over the world.",isbn:null,printIsbn:"978-953-307-047-6",pdfIsbn:"978-953-51-5867-7",doi:"10.5772/150",price:159,priceEur:175,priceUsd:205,slug:"petri-nets-applications",numberOfPages:764,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"b1f80da4d06e2b7b4076e74797319265",bookSignature:"Pawel Pawlewski",publishedDate:"February 1st 2010",coverURL:"https://cdn.intechopen.com/books/images_new/3780.jpg",numberOfDownloads:78076,numberOfWosCitations:13,numberOfCrossrefCitations:19,numberOfCrossrefCitationsByBook:3,numberOfDimensionsCitations:51,numberOfDimensionsCitationsByBook:3,hasAltmetrics:0,numberOfTotalCitations:83,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"July 30th 2013",dateEndSecondStepPublish:"August 20th 2013",dateEndThirdStepPublish:"November 24th 2013",dateEndFourthStepPublish:"February 22nd 2014",dateEndFifthStepPublish:"March 24th 2014",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"4487",title:"Dr.",name:"Pawel",middleName:null,surname:"Pawlewski",slug:"pawel-pawlewski",fullName:"Pawel Pawlewski",profilePictureURL:"https://mts.intechopen.com/storage/users/4487/images/3685_n.jpg",biography:"Paweł PAWLEWSKI, PhD, is Assistant Professor at the Faculty of Engineering Management at Poznan University of Technology. His area of interest comprises: modeling, process simulation and optimization, organization of manufacturing processes, operational management, reengineering and IT applications in logistics. He is the author or co-author of more than 100 scientific papers. He is also co-author of the book “Reengineering”. In 1994-2008 he managed a team performing a software for design and optimization of mechanical structures implemented among other things in VW-Wolsburg, VW-Shanghai, Audi-Ingolstadt, Seat-Barcelona, Porsche-Stuttgart, BMW–Munchen. All actions were taken within vMACH Engineering company. In 2009-2011 he cooperated with AMC Polska company in the scope of process simulation and optimization with the usage of Witness. Since 2011 he is a Manager of Simulation and Optimization Center in Logistic and Production Processes (SOCILAPP) at Poznan University of Technology. Habilitation dissertation titled “ Methodology of modeling dynamic changes of production process’ resource structure in mechanical engineering industry” is under accreditation procedure. Since 2011 he cooperates with Cempel Consulting. He is also a Flexsim Software Products Inc. (USA) Partner in Poland. Since 2012 he is member of Editorial Board (as Associate Editor) of International Journal of Artificial Intelligence (IJAI).",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Poznań University of Technology",institutionURL:null,country:{name:"Poland"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"616",title:"Mathematical Modeling",slug:"theory-of-computation-mathematical-modeling"}],chapters:[{id:"9175",title:"An Application of GSPN for Modeling and Evaluating Local Area Computer Networks",doi:"10.5772/7524",slug:"an-application-of-gspn-for-modeling-and-evaluating-local-area-computer-networks",totalDownloads:1946,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Masahiro Tsunoyama and Hiroei 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Micropropagation as an alternative method to conventional propagation, the culture of somatic cells, tissues and organs of plants under controlled conditions is a suitable way to produce a large number of progeny plants which are genetically identical to the stock plant in a short time. The important property of the plant cells is totipotency which is a capacity to produce the whole plant from different plant parts. Micropropagation has some features to be chosen in commercial production such as multiplicative capacity in a relatively short time, healthy and disease-free production capacity and ability to generate population during a year [1-5].
The genetic pattern of the plant is key element to select the propagation method. Using micropropagation techniques in plant biotechnology applications are costlier than conventional propagation methods. Propagation by using
The main methods of
Propagation from axillary or terminal buds
Propagation by the formation of adventitious shoots or adventitious somatic embryos
The meristem and shoot tip cultures are used to establish virus-free plant culture. Many important horticulture crops were propagated by meristem culture for rapid growth and virus elimination. Adventitious shoots or adventitious somatic embryos are established directly or indirectly. Cultures are directly started with the excised explants from the mother plant tissues for organogenesis or embryogenesis. If shoots or embryos regenerate on previously formed callus or in cell culture, they are called as indirect organogenesis or embryogenesis [3,6,7].
When propagation occurs via an indirect callus phase, the genetic identity of the progenies decreases. This is an important problem in commercial propagation to affect the uniformity of progenies. Callus formation also increases the somaclonal variation. Increasing of somaclonal variation incidence is a crucial result of long term period of callus growth. Origin of the callus also causes somaclonal variation.
Propagation from axillary or terminal buds is the most ensurable method to have the highest genetic stability during
George et al. [2008] described five stages of micropopagation which are mother plant selection and preparation [Stage 0],
Establishing aseptic culture conditions can be classified as Stage 0 which contains pre-surface sterilization applications of explants to reduce contamination of stock plants. The success of Stage 2 depends on different factors such as plant species, cultivar or genotype, plant growth regulators, the ingredients of the medium and physical culture conditions. Stage 3 is responsible of rooting of microshoots. It depends on the factors given in Stage 2. Transplantation of rooted shoots to the environment is the main step of Stage 4. This is also the important part of micropropagation. Acclimatization needs to be well controlled to avoid loss of propagated plants [4,5].
The commercial production of ornamental pot plants has a great potential in international markets. In the global market,
The propagation rate of
The success of tissue culture is related to the correct choice of explants. Shoot or shoot tips and node cultures are the most commonly used culture types in micropropagation of plants. Explants from shoot tips and nodal stem segments are suitable for enhanced axillary branching.
The genotype of
Selection of explant type to induce callogenesis and orgonogenesis is important for plants. In direct and indirect orgonogenesis studies, using young leaf explants are important for the success of culture. Martin et al.[2003] observed higher number of shoots in the brown young lamina explants than young green lamina. Viégas et al.[2007] also indicated the importance of using new brown leaves for callus induction. Bejoy et al.[2008] reported that the explants excised from pale green leaves showed better callus development than pale brown leaves. Atak and Çelik [2009] also used young brown and green leaves of
The second important step in micropropagation is to obtain aseptic culture of plant material. Aseptic culture systems are effective to eradicate the bacterial, fungal and insect contaminants. The sterilization protocols used for different
Leaf | 0.6% Benlate [30 min]+70% ethanol [30 sec]+1.5% NaOCl containing two drops of Tween 20 [20 min] | [15] | |
Leaf | 0.1% HgCl2 | [19] | |
Leaf | 70% ethanol [1 min]+gentamicin [30 min]+20% [v/v] commersial bleach [5% NaOCl,12 min] | [20] | |
Apical shoot buds | Teepol+ antifungal solution Cetrimite [5min.] +NaOCl [5 min]+ 0.1% [w/v] HgCl2 [5min.] | [11] | |
Spadices | Washing under running tap water [30-60 min]+1% pesticide solution of 50% benomyl and 20% streptomycin sulphate [30 min] +5 times distilled water [5min each rinse.]+ 1% NaOCl [10 min] + 2% NaOCl [5min] +80% alcohol [30s.] +5-6 times distilled water [5min each rinse.] | [22] | |
Leaf and spadix Segments | Washing under running tap water [30 min]+0.5% [v/v]Trix [Commercial detergent]+70% ethanol [1 min.] + 1.5% NaOCl containing 0.01% Tween 20 [8 min] | [23] | |
A.andreanum cv Rubrun | Seeds from plant spadix | 1%NaOCl [20 min] | [7] |
Separate fruits from spadix Isolate seeds | 3% [v/v]NaOCl [15 min]+3 times distilled water [5min.] 1% [v/v]NaOCl [20 min]+2 times distilled water [10min.] | [18] | |
Lamina segments | 5% [v/v] Extran [5 min. with detergent]+0.1% [w/v] mercuric chloride [10-12 min] | [1] | |
Leaf | 15% [v/v] commersial bleach [20 min]+0.1%HgCl2 [7 min] | [21] |
Sterilization methods used in
Culture medium influences the propagation efficiency in plant tissue culture applications. Organic compounds, vitamins and plant growth regulators are used to stimulate healthy growth. The rate of tissue growth and morphogenetic responses highly affected by the features of nutrients included.
There are several basal media such as Chu [N6] [24], Gamborg’s B5 [25], Murashige and Skoog [MS] [26], Murashige and Tucker [MT] [27] and Nitsch and Nitsch [NN] [28]. These media are successfully used for establishing tissue cultures of different explants of various plants [22].
In plant tissue culture studies, different combinations of every medium based on different concentrations of macro and micronutrients have been used to develop efficient protocols. The rapid and efficient tissue culture protocols are important for micropropagation of
The success of plant tissue culture depends on the composition of the medium used. Different combinations of macronutrients as nitrogen, potassium, calcium, phosphorus, magnesium and sulphur and micronutrients [trace elements] as iron, nickel, chlorine, manganase, zinc, boron, copper and molybdenum change the nature of the medium.
Each plant species has its own medium composition or it should be improved for better results. The modifications can be made up in macro and micronutrients, sugar content, plant growth regulators, vitamins and other nitrogen supplements.
MS media with some modifications have been frequently applied in tissue culture of
Nitrogen is an essential macronutrient in plant life. It is an important component of proteins and nucleic acids. Nitrate [NO3-] is the main source of nitrogen. NO3- is reduced to ammonium [NH4+] after uptake. Plants have ability to use the reduced form of nitrogen for their metabolism. Nitrate uptake happens effectively in an acidic pH. But after nitrate uptake, the medium are becoming less acid. When ammonium uptake, it makes the medium more acidic. The pH of the plant culture media is important because in a buffered media, existence of both ions affects efficient nitrogen uptake. The form and the amount of nitrogen in media have significant effects on cell growth and differentiation. pH controlling in the media is not the only reason of using both ions, excessive ammonium ions are toxic to the plants. Media containing high levels of NH4+ also inhibits chlorophyll synthesis [4].
It has been known that the root growth is induced by NO3- and reduced by NH4+. But morphogenesis is being controlled by total amount of nitrogen in the medium and it needs both of NO3- and NH4+. Because of using optimum NH4+: NO3- has a key role in morphogenesis, therefore the balance between NO3- and NH4+ differs for different plants and different kinds of cultures. This situation implies that this ratio should be specifically adjusted for each plant species and for different purposes. Changing the NO3- to NH4+ ratio by small alterations affects differentiation and growth.
A.andreanum | Leaf | MS+2.2-4.4µM BA+0.9µM 2,4-D | Adventitious shoots | [33] |
Root | Modified MS+2.2µM BA | Multiple shoots | [34] | |
Leaf | Modified Nitsch [200mg/l NH4NO3] +1mg/l BA+0.1mg/l 2,4-D | Callus initiation | [15] | |
Nitsch [720mg/l NH4NO3] +0.5mg/l BA | Shoot development | |||
Nitsch [720mg/l NH4NO3] +1.0mg/l IBA+0.04% AC | Roots | |||
Leaf | ½MS+0.6mg/l 2,4-D+1mg/l BAP | Callus induction | [20] | |
½MS+250mg/l NH4NO3+0.1mg/l 2,4-D+1mg/l BA | Shoot regeneration | |||
½MS+1mg/l IBA+0.04% AC | Roots | |||
Leaf, spadix | ¼MS+1mg/l BAP | Multiple shoots | [23] | |
¼MS+1mg/l IBA | Roots | |||
Seed | MS+2mg/l BA+0.5mg/l NAA | Callus proliferation | [18] | |
Petiol | ½MS+0.1mg/l 2,4-D+0.5 mg/l BA | Callus | [36] | |
½MS+0.1mg/l 2,4-D+1.0 mg/l BA | Shoot | |||
½MS+0.5mg/l 2,4-D | Root | |||
Leaf | ½MS+1mg/l BA+0.08mg/l 2,4-D | Callus induction | [19] | |
½MS+1mg/l BA | Callus multiplication | |||
½MS[206 mg/l NH4NO3] +1mg/l BA | Shoot regeneration | |||
¼MS+1g/l AC | Roots | |||
Leaf, petiole | Modified Pietrik medium+0.36µM 2,4-D+4.4µM BA | Callus | [32] | |
Microcutting from germinated seed | MS+4.4µM BA+0.05µM NAA | Multiple shoots | [7] | |
Apical shoot bud | MS+0.1mg/l NAA+0.25mg/l BAP | Multiple apical shoots | [11] | |
MS+0.5mg/l BAP+60mg/l adenine sulphate | Multiple shoots | |||
MS+0.5mg/l IAA+2g/l AC | Roots | |||
Half anther culture | NWT+0.25mg/l 2,4-D +0.02mg/l NAA+1.5mg/l TDZ + 0.75 mg/l BAP | Callus Shoot regeneration | [22] | |
NWT+ 0. 2mg/l NAA+1.0 mg/lKIN | Roots | |||
Nodal segments | MS+4.44mM BAP+2.89mM GA3 | Shoot induction | [16] | |
A.andreanum Hort | Lamina | ½MS+1.11µM+BA+1.14µM IAA+0.46µM Kin | Shoot induction | [1] |
½MS+0.44µM BA | Multiple shoots | |||
½MS+0.54µM+NAA+0.93µM Kin | Roots | |||
Leaf | ¼MS+0.88µM BA+0.9µM 2,4-D+0.46µM Kin | Callus | [35] | |
¼MS+0.88µM BA+0.54µM NAA+0.46µM Kin | Multiple shoots | |||
½MS+0.54µM NAA | Roots | |||
½MS+0.5mg/l 2,4-D+1mg/l BAP | Adventitious shoots | [21] | ||
Leaf, petiole | ½MS+0.90µM 2,4-D+8.88µM BA | Callus induction | [17] | |
½MS+0.90µM 2,4-D+4.44µM BA | Callus proliferation | |||
MS+5.71mM NAA | Roots | |||
Leaf | ½MS+0.08mg/l 2,4-D+1mg/l BAP+1mg/l 2-iP | Callus | [10] | |
MS+0.5mg/l BAP | Shoots | |||
Leaf | Modified MS+2.5 mM NH4NO3+18µM 2,4-D+6% sucrose | Embryo induction | [6] |
MS media used frequently for tissue culture of Anthurium and the ratio of NO3- to NH4+ is 66:34 at this medium. For this reason generally modified MS medium used at Anthurium organogenesis. The modifications of ammonium nitrate concentration have been studied at Anthurium media by researchers. Hamidah et al. [1997] used half-strength MS macroelements with 2.5 mM ammonium nitrate for in vitro stock cultures. While Puchooa [2005] used 200 mg/L reduced ammonium nitrate concentration for callus culture, they increased the amount to 720 mg/L for regeneration. Dufour and Guérin [2005] used different compositions of NO3 and NH4 to evaluate the developmental results. According to their results, the ratio of 0.37 showed better plant growth and development. Atak and Çelik [2009] preferred to use half-strength MS salts with NH4NO3 lowered to 250 mg/L for shoot regeneration. Winarto et al. [2011] were improved a protocol for callus induction and plant regeneration and NWT-3 media contains 750 mg/l NH4NO3.
In culture conditions, using synthetic chemicals with similar physiological activities as plant hormones have capabilities to induce plant growth as desired. Auxin and cytokinins are the most important hormones regulating growth and morphogenesis in plant tissue culture. Their combinative usage promote growth of calli, cell suspensions, root and shoot development and have capability to regulate the morphogenesis [4,29]. There are synthetic auxin and cytokinins beside naturals. Different combinations and concentrations of plant growth regulators such as 2,4-dichlorophenoxyacetic acid [2,4-D], naphthalene acetic acid [NAA], benzylaminopurine [BAP] and kinetin [Kin] were used to indicate callus formation from different kinds of explants of Anthurium cultivars. In preliminary studies, induction and regeneration of callus followed by shoot and root regeneration are the main steps of tissue culture of whole plants. As an important commercial plant, to develop a rapid and more effective tissue culture protocol to shorten the time is the main objective of Anthurium tissue culture [7,10, 22,23].
As given in Table 2, combination of 2,4-D and BA in culture media to induce callus initiation from leaf explants in different varieties of Anthurium is frequently used. Also, adding of BAP and 2-iP to the callus medium has been evaluated by different researchers. The concentrations of 2,4-D used in the callus medium is ranging from 0.08 mg/l to 1 mg/l 2,4-D. The BA concentrations are changing between 0.1 mg/l and 1 mg/l.
Micropropagated plants require a developed root system to resist the external environmental conditions. Rooting of the shoots take place in vitro. Therefore, determination of the appropriate auxin type and levels in the media required to promote rooting [4].
Activated charcoal [AC] is added to medium for promoting root growth [11, 13, 15, 19, 20]. AC is composed of carbon and it is often used in plant tissue culture to absorb gases and dissolved solids. It is not a growth regulator but it has an ability to modify medium composition [4].
There are several advantageous uses of charcoal on the type of culture. These are adsorption of secreted compounds from cultured tissues, decrements in the phenolic oxidations, pH changes of the medium to optimize for morphogenesis, prevention of unwanted callus growth, simulation of soil conditions because of the ability to promote root formation, capability to use in production of secondary plant products in culture conditions [4, 30].
The most important effect of using AC to the medium is the rigorous decrease in the concentrations of plant growth regulators and other organic supplements. AC shows greater adsorptive capacity to phenolics commonly produced by wounded tissues, plant hormones like IAA, NAA, IBA, BA, kinetin, zeatin and other hormones [30,31]. The adsorptive property of AC changes with purity, pH and density [3]. The Anthurium seedlings propagated by Atak and Çelik [2009] were rooted in medium containing AC and given in Figure 1.
In vitro propagation of Anthurium cultivars [Arizona]. The shoots with root were growth inplant tissue culture medium with AC [
In plant propagation applications, subculturing has an importance to prolong the life of plants and expand the number of cultured seedlings. At in vitro propagation of Anthurium andreanum cultivars, the number of shoots per explants was increased subsequent subcultures. Atak and Çelik [2009] observed that shoot multiplication for two Anthurium andreanum cultivars Arizona and Sumi was increased in the next multiplication stage. At every subculture, shoot numbers regenerated form nodal explants gradually increased [Table 3]. Bejoy et al.[2008] reported that multiplication was enhanced in the next multiplication stage. They succeeded to increase the rate of shoot production in the second multiplication stage.
Subculture | Subculture | ||||
Number of Explants | Number of Shoots per Explant | Number of Explants | Number of Shoots per Explant | ||
50 | 15. 64±1.69a | 50 | 12.24±1.18a | ||
50 | 22.70±1.46b | 50 | 15.98±1.36b | ||
50 | 26.76±1.30c | 50 | 21.82±1.87c | ||
50 | 33.70±1.09d | 50 | 26.96±1.46d |
Shoot multiplication of Anthurium andreanum cultivars [20].
In micropropagation studies, the last and the critical step is acclimatization of the rooted seedlings to the environment. In this stage, plant losses have been due to different reasons [37,38]. Directly rooted shoots in soil show higher survival rate in the field than rooted under in vitro conditions. Therefore, there are several methods to high the survival rate of in vitro rooted shoots.
Cultured plants must adapt to low humidity, high light intensities and large temperature fluctuations with ex vitro acclimatization techniques. However these methods are expensive, time consuming and labor-intensive, in vitro acclimatization techniques have been improved. Using growth chambers which have relative humidity, controlled ventilation and possibility to change the components of the media make it possible to reduce the steps need for the process [37,39].
The success of acclimatization of in vitro cultured plants depends on the nutrients reserved in the leaves during development [40]. The important point in acclimatization is to keep the rooted plants in incubator in order to keep the humidity high.
Different acclimatization protocols for in vitro regenerated A.andreanum plantlets have been reported. Soilrite-perlite with the rate of 10:1, vermicompost and sand mixture [1:3], vermiculite and perlite [1:1], soil and organic humus [1:1] are the most used acclimatization mediums with the high survival ratios ranging from 60% to 98% [1,10,13].
During in vitro development stage, the cultural conditions such as humidity, air turbulence, CO2 concentration, sugar content in medium effect acclimatization ability of plants to ex vivo conditions. Therefore, for each Anthurium varieties, efficient acclimatization protocols have to be improved to prolong the success of micropropagation.
In micropropagation studies, the success of the protocols depends on the variety of Anthurium, explant type, the components of the media used for shoot and root regenerations. Different combinations of plant growth regulators and additives used in relation to increase the regeneration potential of the explants should be evaluated for each cultivars to determine the efficient tissue culture protocol. In this chapter, we compared the explant types and tissue culture components for Anthurium species which is an important ornamental pot plant.
Stages of the leaves show different response to propagation by indirect organogenesis. Explants prepared from brown leaves have higher callus formation rates in a shorter time than green leaf explants. Therefore, selection and using the right leaf explants at the appropriate leaf stage is the first step of establishing a successful tissue culture. Using different combinations of plant growth regulators and nitrogen additives should be evaluated to control the organogenesis for Anthurium varieties. NO3- : NH4+ balance in the growth medium has to be adjusted for each Anthurium varieties to obtain desired differentiation and growth. Developing an ideal acclimatization condition is important to increase the survival rate of micropropagated and rooted seedlings to adapt to ex vivo conditions.
In conclusion, the primary point to be remembered is the effects of genotypical differences on culture efficiencies. Different genotypes of varieties show different organogenesis responses in explant cultures. Therefore for each Anthurium varieties suitable micropropagation methods should be determined.
The most vulnerable portion of the implantable cardiac pacemaker system is the transvenous lead(s), which can dislodge, fracture, experience insulation breach, and may lead to a host of adverse events including perforation, venous occlusion, tricuspid regurgitation, oversensing (with inappropriate device function), and infection. The innovation of a leadless pacemaker offers pacing support through a catheter-delivered device that is situated entirely within the right ventricle. A leadless pacemaker eliminates the need for both a pacemaker pocket and transvenous access. Its main limitations are lack of atrial pacing and sensing capabilities and the inability to provide antitachycardia pacing. For patients who require solely single-chamber ventricular pacing (VVI/R), the leadless pacemaker offers an important new option. Growing experience with these leadless devices shows great promise and expanding applications, even though real-world clinical experience is limited. The Spanish Pacemaker Registry reported about 1.6% leadless pacemakers out of all 12,697 reported devices by 2016 [1]. Despite this slow uptake, leadless pacing systems may be an important “disrupting technology” in cardiac rhythm management.
There are currently two commercially available leadless pacemakers, which are designed to reside entirely within the right ventricle, affixed to the ventricular septum either mid-way or near the apex (see Figure 1). These devices are manufactured by two of the leading pacemaker companies in the world: Medtronic makes the Micra™ leadless pacemaker and Abbott (formerly St. Jude Medical) the Nanostim™ leadless pacemaker. The devices are cylindrical, attach directly to right ventricular septum, and have pacing and sensing electrodes that adhere to the myocardium with a retrieval loop on the other end of the device to facilitate extraction.
The leadless pacemaker is implanted via a catheter into the right ventricle and affixed near the apex or midway on the right-ventricular septum where the operator attains acceptable electrical measurements (capture threshold, R-wave amplitude, and pacing impedance). The integral pacing and sensing electrodes in the device eliminate the need for transvenous pacing leads (illustration by Todd Cooper).
Leadless pacemakers are capable of pacing in the VVI mode with the programmable option of rate response (VVIR). The Medtronic device contains a lithium-silver-vanadium-oxide/carbon monofluoride battery (120 mAh), while the Abbott device utilizes a lithium carbon monofluoride battery with 248 mAh [2]. Both devices weigh about 2 g; the Abbott device (Nanostim™) is longer and thinner (42 mm in length and 5.99 mm diameter), while the Medtronic device (Micra™) is shorter and thicker (25.9 and, 6.7 mm) [2]. The Abbott device is secured via an active-fixation type helix mechanism, while the Medtronic device relies on passive fixation with nitinol tines [3]. Battery longevity in leadless pacemakers is estimated to be about 12–14 years. The Abbott (Nanostim™) leadless pacemaker was the subject of a global alert in late 2016 because of premature battery depletion that could result in loss of output and telemetry. The battery is a proprietary lithium-carbon monofluoride cell. Of 1423 Nanostim™ implantations around the world, 34 batteries failed (about 2%), but without any associated patient injury [4].
Leadless pacemakers at present cannot offer dual-chamber pacing modes or antitachycardia pacing; thus, they are only appropriate for patients who require VVI/VVIR or VOO/VOOR pacing. Electrogram storage is possible but there is limited device memory compared to transvenous pacemaker systems [5].
Leadless pacemakers are typically implanted via right or left femoral venous access into the septal wall of the right ventricle, although a right internal jugular vein approach has been described in the literature [6]. Right femoral access is preferred as the femoral iliac system nothing is less sharply angled on this side at the point where it joins the inferior vena cava [7]. The outer delivery sheath needed to deliver the pacemaker may have a diameter of 27 French (9 mm), which can be accommodated at implant by using a step-up sequence of dilators. Ultrasound with or without micropuncture has been recommended to avoid accidental arterial puncture or suboptimal sites of femoral puncture. As delivery sheaths may be large caliber, a poorly positioned puncture may make hemostasis challenging at the point when the sheath is withdrawn [7]. The proprietary delivery catheter is deflectable and advances with the device via the superior or inferior vena cava into the right atrium, over the tricuspid valve, and then into the right ventricle. The delivery catheter releases the device, which is affixed by active- or passive-fixation mechanisms to the endocardium [7]. Fluoroscopy may be used to confirm appropriate position. On radiography, the implanted devices look like a small cylinder (about the size and shape of a triple-A battery) [8]. Appropriate position is confirmed with acceptable electrical measurements generally defined as capture threshold ≤1.0 V at 0.24–0.4 ms, R-wave >6 mV, and impedance >500 Ω. The introducer sheath is then detached and removed and hemostasis achieved by a closure device, sutures, or manual pressure [7].
Unlike pacing thresholds with transvenous systems, which tend to gradually rise weeks after implant, the capture threshold for a leadless device may be expected to decrease somewhat about 30 min after implant and then stabilize. In two cases reports, threshold values in for a leadless pacemaker (Nanostim™) decreased markedly during the perioperative period. In one case, the pacing threshold was >6.5 V, the initial R-wave was >12.0 mV, and impedance was 1830 Ω. Rather than reposition the system, it was decided to wait for 30 min, at which time the pacing threshold was 2.25 V at 0.4 ms and impedance dropped to 1520 Ω. The same report described another case in which the pacing threshold was >6.5 V and impedance was 1330 Ω, but after allowing 25 min to elapse, the capture threshold decreased to 2.0 V at 0.4 ms and impedance was measured the next day at 800 Ω [9]. In fact, thresholds continued to improve in both cases the day after implant. It has been speculated that acute injury caused by the extension of the active-fixation helix being screwed into the myocardium might cause an increase in threshold that attenuates rapidly [9]. Thus, it may not always be necessary to reposition the device during implant in order to obtain adequate thresholds; instead, it requires a perioperative waiting period.
As with other implanted devices, operator experience may help reduce adverse events at implant. In an analysis of all patients implanted with a leadless pacemaker (Nanostim™) in the LEADLESS and LEADLESS II clinical trials (n = 1439), 6.4% of patients experienced a serious adverse device effect (SADE) in the first 30 days after implant, but SADE rates dropped significantly from 7.4 to 4.5% (p = 0.038), once the operator had more than 10 implants. Over time, the need for device repositioning likewise decreased with operator experience, from the first quartile (26.8%) to the fourth quartile (14.8%), p < 0.001 [10]. This suggests that there is a learning curve for leadless pacemaker implantation, not unlike that for other implantable devices, such as cardiac resynchronization therapy systems and subcutaneous implantable cardioverter defibrillators. The most frequently reported adverse events were cardiac perforation (24 events, 1.7% of patients) followed by device dislodgement (20 events, 1.4%) and tamponade (18 events, 1.3%) [10].
The leadless pacemaker is shipped already programmed to VVI pacing. It is sometimes helpful to switch the device to VOO during implant, for example, to better manage a pacemaker-dependent patient or if electromagnetic devices used during implant could potentially interfere with the pacemaker. A conventional transvenous pacemaker can be set to VOO mode perioperatively with simple magnet application, but this is not possible with some leadless pacemakers. Instead, the manufacturer or other expert team should be consulted in the event that the leadless pacemaker must be implanted in VOO mode [11].
Implant success rates are high with leadless devices. In the LEADLESS study (Nanostim™), the pacemaker could be implanted successfully in 95.8% of patients with a procedural time of 28.6 ± 17.8 min and fluoroscopy time of 13.9 ± 9.1 min [3]. In a study at a Polish single center, 10 patients were successfully implanted with a leadless pacemaker (Micra™), which was implanted with a mean implant duration of 82 min and mean fluoroscopy time of 3.5 min [12]. In a case series of five leadless pacemaker (Micra™) patients, the average duration of implantation procedure was 47 ± 11 min, which appeared to shorten over the series from a peak of 65 (second case) to 38 min for the last case [13]. In this case series, the mean capture threshold was 0.53 ± 0.27 V at 0.24 ms and mean R-wave was 13 ± 5.8 mV with no cases of acute dislodgement [13]. A study of 92 patients with leadless pacemakers (Micra™) at a Swiss single center found median capture thresholds at implant were 0.38 V at 0.24 ms (range 0.13–2.88 V at 0.24 ms), which remained stable throughout 1 year of follow-up [14]. In a case series of five leadless pacemaker patients (Micra™), all of the devices were successfully implanted [13]. A study of leadless pacing (Micra™) in Japan enrolled 38 patients at four sites and reported an implant success rate of 100% and the rate of freedom from major complications at 1 year was 96%. At 6 months, 98.3% had low, stable capture thresholds [15].
A prospective multicenter uncontrolled study enrolled 725 patients with an indication for single-chamber pacing to be implanted with a leadless pacemaker (Micra™). The primary endpoint was the percentage of patients with low, stable electrical capture thresholds at 6 months, defined as ≤2.0 V at 0.24 ms that increased ≤1.5 V from implant. The device could be successfully implanted in 719/725 patients (99.2%), and 96.0% met the primary endpoint at 6 months. At 6 months, the mean capture threshold was 0.54 V at 0.24 ms with an R-wave of 15.3 mV and 627 Ω impedance. The majority of patients (91%) had a pacing output of <1.5 V at 0.24 ms at 6 months, which implies that battery longevity should exceed 12 years [16]. A total of 28 major complications were reported in 25/725 patients, but no devices dislodged. Those complications included cardiac injuries (n = 11), complications at the puncture site in the groin (n = 5), thromboembolism (n = 2), pacing problems (n = 2), and other complications (n = 8). In total, three patients required device revision (two had elevated capture thresholds and one had pacemaker syndrome) and devices were deactivated (OOO mode) and abandoned; a transvenous pacing system was implanted. One patient had the device explanted because of transient loss of capture and a new leadless pacemaker was implanted [16].
A worldwide postapproval registry of the Micra™ device reported 99.1% rate of successful implantations in 1817 patients with a one-year major complication rate of 2.7% (95% confidence interval [CI], 2.0–3.7%), 63% lower than the rate of major complications for transvenous pacemaker patients (hazard ratio 0.37, 95% CI, 0.27–0.52, p < 0.001). In this study, there were three instances of device infection, none of which required device extraction [17].
A single-center registry of 66 patients undergoing leadless pacemaker implantation (Micra™) reported that the indications in this population were third-degree atrioventricular block, sinus node dysfunction, or permanent atrial fibrillation with bradycardia (30.3, 21.2, and 45.5%, respectively). Implant success was achieved in 65/66 patients, and electrical measurements were stable over the follow-up period of 10.4 ± 6.1 months. At the last follow-up, the mean capture threshold was 0.57 ± 0.32 V, the mean R-wave was measured at 10.62 ± 4.36 mV, and the mean impedance was 580 ± 103 Ω. In this study, one patient experienced a major adverse event (loss of device function) and there were three minor adverse events [18].
A single-arm observational study based on a postapproval registry of Micra™ leadless pacemakers reported a 99.6% success rate in device implants (792/795 patients) at 96 centers in 20 countries. At 30 days after implantation, 13 major complications were reported in 12 patients (1.51% complication rate, 95% CI, 0.78–2.62%) [19]. In a Swiss retrospective observational study of 92 Micra™ patients, the serious adverse event rate was 6.5% (n = 6), resulting in extended hospitalization for five patients and one death; three other adverse events occurred over the one-year follow-up (3.3% of patients, n = 3), resulting in revision to a conventional transvenous pacemaker in two patients and extraction of the pacemaker in the third because of ventricular tachycardia [14].
Physician acceptance of leadless pacing appears to be high. A study of leadless pacing (Micra™) in Japan enrolled 38 patients, and most of the implanting physicians said the leadless pacemaker was “extremely easy” or “easy” to implant (91.6%) and deploy (94.4%) [15].
The prospective, single-arm, multicenter LEADLESS observational study (n = 470) evaluated the freedom from serious adverse device events at 6 months as the primary endpoint. The study had to be interrupted owing to the occurrence of cardiac perforation events that required changes in the protocol and training. In the 300 patients enrolled after the study interruption, freedom from serious adverse device events was 94.6% (95% CI, 91.0–97.2%), although 18 serious adverse device events were observed in 6.6% of patients (n = 16), the most frequent of which were perforation (1.3%), vascular complications (1.3%), and dislodgement of the device (0.3%). When all 470 patients were included (before and after the interruption), 6.6% of all patients experienced a serious adverse device-related event [20].
The LEADLESS clinical trial retrospectively evaluated safety and efficacy of the Nanostim™ leadless pacemaker over a minimum of 3 years of follow-up. A total of 33 patients (mean age 77 ± 8 years) were enrolled, of whom 31 received a leadless pacemaker [21]. Two patients could not be implanted (one procedure was aborted and the other was revised to an ICD.) At 3 years, 74% (23/31) of patients were alive and no deaths were attributable to the leadless pacemaker. Most patients (89.9%) reported freedom from serious adverse events (95% CI, 79.5–100%), and 9% experienced device-related complications, of whom two had procedure-related serious adverse events. One suffered perforation leading to tamponade and the other had inadvertent implantation of the leadless pacemaker into the left ventricle by way of a patent foramen ovale, which was successfully retrieved and a new device implanted into the right ventricle. A third complication was reported after 37 months attributed to battery malfunction and necessitating device revision, which involved the successful removal of the leadless pacemaker and replacement with a new one. Up to 35 months, the electrical parameters of the leadless pacemakers were appropriate [21]. A retrospective assessment of 31 of the 33 patients from the LEADLESS study was conducted to evaluate the complication rates, device performance, and rate response features at 1 year. No pacemaker-related adverse events occurred from 3 months postimplant to 12 months. At 12 months, the mean pacing threshold was 0.43 ± 0.30 V at 0.4 ms, the mean R-wave was 10.3 ± 2.2 mV, and 61% had rate response features activated, of whom adequate results were achieved by all [22].
The LEADLESS II study is a premarket, nonrandomized, prospective, multicenter study of 526 patients with a leadless pacemaker (Nanostim™) who were followed for safety and efficacy for 6 months [3]. Inclusion criterion was a single-chamber ventricular pacing indication (which included patients with persistent or permanent atrial fibrillation). The primary efficacy outcome was achievement of a therapeutic capture threshold (defined as ≤2.0 V at 0.4 ms) and appropriate sensing (≥5.0 mV R-wave or an R-wave that exceeded the R-wave value at implant). By an intention-to-treat analysis, 90.0% of patients in the primary cohort achieved this at implant. At 12 months, the mean capture threshold was 0.58 ± 0.31 V at 0.4 ms and the mean R-wave was 9.2 ± 2.9 mV. At 12 months, the mean percentage of ventricular pacing was 51.6 ± 39.1%. The primary safety outcome was freedom from device-related adverse events in the first 6 months after implant, which was achieved by 93.3% of patients. Over 6 months, a total of 22 serious adverse events related to the device occurred in 20 patients (6.7%) in the primary cohort. In the total cohort, the rate of serious adverse events related to the device was 6.5%. Devices migrated from the heart into the pulmonary artery or right femoral vein in four and two patients, respectively, and all devices were successfully retrieved percutaneously [3]. The majority of patients did not require revision to reposition the pacemaker (70.2%), but 4.4% of patients required two or more attempts to reposition the device. The mean duration of hospital stay was 1.1 ± 1.7 days (range 0–33) [3]. Over the course of the study, 28 patients died (5.3%) but no deaths were related to the device.
The LEADLESS II patient cohort (n = 718) was compared retrospectively to 1436 transvenous pacemaker patients (historical data) with the results that leadless pacemaker patients had fewer complications (hazard ratio 0.44, 95% CI, 0.23–0.60, p < 0.001) broken down as short-term complications (5.8 vs. 9.4%, p = 0.01) and mid-term complications (0.56 vs. 4.9%, p < 0.001). Specifically, leadless pacemaker patients had more pericardial effusions (1.53 vs. 0.35%, p = 0.005), but similar rates of vascular events (1.11 vs. 0.42%, p = 0.085), dislodgements (0.97 vs. 1.39%, p = 0.54), and generator complications (0.70 vs. 0.28%, p = 0.17). Leadless pacemaker patients had no cases of thoracic trauma compared to 3.27% of transvenous patients [23].
In October 2016, an advisory was issued for the Nanostim™ device regarding premature battery depletion [24]. A prospective, observational, single-center study was conducted in Germany with patients implanted early (up until April 2014) or late (starting December 2015 and thereafter). The cohort included 14 consecutive patients (77 ± 9 years, 57% male) with a mean follow-up of 29.5 ± 11.5 months (range 11.9–44.6 months). Most were “early” patients (n = 9, 64%) implanted before the implantation suspension and five were implanted “late” (36%). From data obtained at the last follow-up, 57% had permanent atrial fibrillation with complete heart block, 21% were considered pacemaker dependent, and 36% had a mean regular escape rhythm of 37 ± 2 beats per minute (bpm). Almost half of the patients had signs of battery malfunction (43%, n = 6), all of whom had “early” implants. Using the Kaplan-Meier method, the mean time calculated from implant to device failure was 39.0 months (standard error 1.85 months, 95% CI, 35.4–42.7 months). Device parameters fell within the normal range for all patients (100%) at the last follow-up before battery malfunction was detected. Devices were explanted and analysis showed reduced electrolytes in the lithium carbon monofluoride battery, which caused high internal battery resistance, reducing the available current for device function. While a report from 2016 showed Nanostim™ battery malfunction occurred at a global rate of 2.4%, the rate at this particular institution was much higher, possibly owing to the fact that the observation period was longer [24].
In a meta-analysis of lead and device dislodgement (n = 18 studies, 17,321 patients) involving conventional transvenous pacemakers and leadless pacemakers (both Micra™ and Nanostim™), the weighted mean incidence of lead dislodgement in transvenous devices was 1.71%. Atrial leads had a higher dislodgement rate than ventricular leads (odds ratio 3.56, 95% CI, 1.96–6.70). The dislodgement rate for leadless devices was reported in three studies (n = 2116) and was 0, 0.13, and 1.0%, respectively, showing an overall lower dislodgement rate than conventional systems [25].
In a propensity score-matched study, 440 pacemaker patients were matched based on whether they had a leadless system (n = 220) or a transvenous system (n = 220). The complication rate at 800 days of follow-up was significantly lower in the leadless pacemaker group (0.9 vs. 4.7%, 95% CI, p = 0.02) [26].
Ventricular arrhythmias after the implantation of a leadless pacemaker should be considered as potential side effect secondary to leadless pacemaker implantation. A case report in the literature describes a patient who experienced short episodes of polymorphic ventricular tachycardia (VT) in the perioperative period and high ventricular rates with short-long-short runs of polymorphic VT induced by premature ventricular contractions. The system was extracted successfully, revised with a new device of the same type successfully implanted at a different position in the right ventricle, and the VT resolved. The pro-arrhythmic effect of the leadless pacemaker remains to be elucidated, but it may involve the irritation of the right-ventricular myocardium at the site of implantation [27].
Both commercially available systems offer rate response. The Micra™ device utilizes a programmable accelerometer that works on three axes. Rate response is set up based on three activity vectors. The accelerometer can be programmed following a five-minute exercise test, which should be conducted before hospital discharge and then at an in-clinic visit later. While Vector 1 can be programmed as the nominal setting, an early study in 51 patients (278 tests, 818 vector measurements) found the manual selection of a vector produced better results than opting for the default Vector 1 setting. In initial testing, Vector 1 was found to be adequate in 74.5% of patients but in in-clinic testing, Vector 1 was adequate for 64.7%, while Vector 3 was adequate in 68.6% (and Vector 2 was adequate in 51.0%) [28]. The Nanostim™ device utilizes blood temperature for its rate response [2].
In the LEADLESS clinical trial (n = 31), rate response was turned on in 61% of patients at 12 months, 42% at 24 months, and 39% at 36 months [21].
The Micra™ leadless pacemaker offers a capture management system, while the Nanostim™ does not.
Application of a magnet over the implant site of a conventional transvenous pacemaker will cause it to behave in highly specific ways (for example, asynchronous fixed-rate pacing) in response in a function known as magnet mode. The Micra™ device does not offer magnet mode, but the Nanostim™ will pace at 100 bpm for eight beats and then go to asynchronous pacing at 90 bpm (or 65 bpm if the device is at the elective replacement indicator) [5].
The MIMICRY study (Monocenter Investigation Micra™ MRI Study) examined magnetic resonance imaging (MRI) compatibility in 15 leadless pacemaker patients undergoing either a 1.5 Tesla (T) or 3.0 T cardiac MRI scan; one patient was excluded from the study because severe claustrophobia precluded an MRI. Device parameters remained stable during the MRI and over the one and three-month observation points nothing showed MRI scans were safe and feasible [29]. In an
A case report describes an 85-year-old woman with bradycardia and atrial fibrillation who received a leadless pacemaker (Micra™) and underwent external electrical cardioversion with three shocks at 100, 200, and 360 J. The three cardioversion shocks had no observable effect on the implanted leadless pacemaker [31].
To date, there is limited experience with normal, expected end-of-life device revision. Revision may be accomplished by retrieving the old device and implanting a new one, or by simply inactivating the exhausted device and adding a new device nearby. In theory at least, device retrieval seems preferable, in that it limits the amount of hardware in the body and might reduce long-term complications or device-device interference [32]. Successful acute and chronic device retrievals have been reported in the literature. A study on human cadaver hearts has demonstrated that it is feasible to simply implant a new leadless pacemaker without removing the old one [33]. Successful device extraction in a porcine model was reported using a single-loop retrieval snare and a superior vena cava approach [34].
In a study of Micra™ pacemaker revisions, 989 implants were analyzed and compared to 2667 control patients with a transvenous ventricular single-chamber pacemaker. The actuarial rate for device revision at 24 months following implant was 1.4% for leadless pacemakers (11 revisions in 10 patients) compared to 5.3% in the transvenous pacemaker group (123 revisions in 117 patients), that is, 75% lower for leadless pacemakers (95% CI, 53–87%, p < 0.001). The main reasons for extracting a leadless device were a need for a different device therapy, pacemaker syndrome, and prosthetic valve endocarditis. No leadless pacemaker was extracted because of device dislodgement or device-related infection. In seven cases, the device was deactivated and abandoned; in three cases, the device was extracted percutaneously; and in one case, the device was removed during aortic valve surgery. Overall, 64% of deactivated leadless pacemakers were left
In a retrospective study of 40 successful retrievals of leadless pacemakers (Micra™), 73% (n = 29) consented to supplying procedural details to a research study by Afzal and colleagues. This largest retrieval study to date differentiated between “immediate retrievals” (n = 11) in which the original device was retrieved perioperatively and “delayed retrieval” (n = 18) in which the retrieval involved a new procedure at a later date. The median duration between implant and retrieval in the delayed retrieval group was 46 days (range 1–95 days). The most commonly reported reasons for leadless pacemaker retrieval were elevated pacing threshold upon tether removal (immediate retrieval) and elevated threshold, endovascular infection, or need to switch to transvenous system (delayed retrieval) [36]. The mean duration for a retrieval procedure was 63.11 ± 56 min with a mean fluoroscopy exposure of 16.7 ± 9.8 min. Retrieval was accomplished using a snaring system deployed via a delivery catheter or steerable sheath. No serious complications were reported [36].
In the LEADLESS II trial, the implantable device was retrieved successfully and without complications in seven patients at 160 ± 180 days (median 100 days, 1–413 range). Of these patients, three were implanted with a new leadless pacemaker, two were implanted with a conventional transvenous pacing system, and two patients were implanted with a cardiac resynchronization therapy (CRT) device for heart failure. In a study composed of leadless pacemaker patients who required leadless pacemaker removal from three other multicenter studies, 5/5 patients who required acute extraction (within 6 weeks of implant) and 10/11 of patients who required chronic extraction (≥6 weeks after implant) experienced successful device retrieval with no procedure-related adverse events [37].
Acute explantation of the leadless device was reported in the literature when the device migrated into the pulmonary artery a few days after implantation in a 34-year-old patient with infective endocarditis. A single-loop snare guided by a steerable sheath was used to retrieve the migrated device, and a second leadless pacemaker was successfully implanted with no further complications [38]. A case report describes a 62-year-old pacemaker patient who had a leadless pacemaker implanted (to replace an infected transvenous system) and then revised with a second leadless pacemaker because of failure to capture at maximum output settings. The procedure was conducted by implanting the new leadless pacemaker into the patient, assuring its proper function, and then extracting the original underperforming leadless device using a triple-loop snare system [39]. A single-center case series reported extraction of leadless pacemakers (Nanostim™) in three cases with 100% success rate and fluoroscopic exposure times of 12, 16, and 19 min. Each extraction was preceded by a transesophageal 3D echocardiogram to assess the device’s mobility with the heart and possible endothelialization. Retrieval was carried out using the proprietary catheter system from the manufacturer [40].
A novel extraction technique using a cryoballoon steerable sheath together with a snare was reported for the successful retrieval of a leadless pacemaker (Micra™), which was securely positioned in the patient but had an unusual subacute rise in pacing threshold [41]. The pacemaker was first implanted at the right-ventricular apex, but pacing thresholds were too high there (1.63 V at 0.24 ms), so the device was repositioned to a site on the right-ventricular septum with acceptable thresholds (0.75 V at 0.24 ms). The threshold increased unexpectedly over the next 30 min to 2.2 V at 0.24 ms with no radiographic proof of dislodgement. Using a 15 French steerable cryoballoon sheath in an introducer to the right atrium, the sheath could be navigated over the tricuspid valve and into the right ventricle. A 7 French 20 mm snare was then introduced into the steerable sheath. The retrieval loop on the leadless pacemaker was successfully snared and could be extracted along with the introducer and sheath. No blood clot or visible defect was found on the extracted device. A second leadless pacemaker was implanted at the mid-septum of the right ventricle with good electrical measurements (capture threshold 0.5 V at 0.24 ms), which remained stable over 30 minutes. At 1 month, the patient has a capture threshold of 0.62 V at 0.24 ms, an R-wave of 8.6 mV, and impedance of 600 Ω [41].
Of 1423 leadless Nanostim™ pacemakers implanted around the world, there were 34 reported cases of premature battery depletion with a 90.4% successful retrieval rate even though these were chronic implants (battery depletion occurred at 2.9 ± 0.4 years). Of the seven patients in whom retrieval was not possible, most cases were caused by an inaccessible or otherwise nonfunctional retrieval loop on the device [4].
In a study of health-related quality of life using the Short-Form 36 (SF-36) questionnaire at baseline, 3 months, and 12 months in 720 Micra™ patients, all domains improved significantly at 3 and 12 months compared to baseline values and 96% were “satisfied” or “very satisfied” with the aesthetic appearance of the system, 91% with their recovery, and 74% with their current activity level [42]. Leadless pacemakers were associated with fewer restrictions on activity than leadless pacemakers in a survey of 720 patients [42].
In a study of leadless pacemaker (Micra™) patients, some national differences emerged. In this study, 35 Japanese patients were reviewed compared to 658 similar patients outside of Japan. Fewer Japanese-only patients compared to outside-Japan patients were “very satisfied” or “satisfied” with their recovery (74.3 vs. 91.8%, p = 0.002), but those who reported themselves “very satisfied” or “satisfied” with the device’s cosmetic appearance were similar (91.4 Japanese vs. 96.2% outside Japan). All implants in the Japanese patients were successful [15].
Leadless pacemakers are indicated for patients with symptomatic bradycardia requiring single-chamber ventricular bradycardia pacing support; persistent atrial tachyarrhythmias in such patients are not a contraindication for leadless pacing. In fact, many patients who receive a leadless pacemaker have persistent or permanent atrial fibrillation with slow ventricular response.
The role of leadless pacemakers following removal of an infected conventional transvenous pacing system is debated. Since a leadless device requires no pocket formation and has no transvenous leads, it would appear to be suitable for a revision system for appropriate patients. In a study of patients who required device replacement after a conventional pacemaker system was infected (n = 17), patients were implanted with a Nanostim™ (n = 11) or Micra™ (n = 6) device [43]. In six patients, the leadless pacemaker was implanted within a week or less while in 11 patients, the leadless pacemakers was implanted after at least 1 week. In all patients, there was no infection over the course of a mean follow-up of 16 ± 12 months. This patient population included seven patients with a history of recurrent device infections (mean follow-up of 20 ± 14 months). This study suggests that a leadless pacemaker may be a viable revision pacing system for selected patients who experienced device infection with a conventional pacemaker [43].
The French Working Group on Cardiac Pacing and Electrophysiology of the French Society of Cardiology has issued specific guidelines on leadless pacing [44]. Currently, the indication for leadless pacing is a patient indicated for VVIR pacing and the patient’s life, as well as device service life must be taken into account as device retrieval may not always be possible. They consider that leadless devices should be implanted only in centers that also perform cardiac surgery, because of the higher incidence of tamponade, vascular complications, perforations caused by large-diameter sheaths, or other complications associated with leadless pacemakers [44].
It has been recommended that anesthesiologists familiarize themselves with all implantable device technologies, including leadless pacemakers [5]. A challenge to these devices is that interrogation software may not be readily available and that implantation should be coordinated with device manufacturer representatives or cardiologists, for example, if the device should be programmed to an asynchronous pacing mode during implant [5].
In 64% of patients enrolled in one of the pivotal trials for leadless pacemakers (Micra™), the pacing indication was managing persistent or permanent atrial fibrillation with slow ventricular response [16]. In that pivotal trial, only 6% of patients had a clear-cut medical reason that limited or contraindicated them from a transvenous system. However, there are many emerging groups who may derive benefits from leadless pacemakers.
Leadless pacemakers may be an important alternative to conventional devices in patients with thromboses, venous obstruction, tortuous or abnormal venous anatomy, superior vena cava syndrome, or other conditions may be contraindicated for a conventional transvenous pacemaker. A case report describes a patient with third-degree atrioventricular (AV) block who experienced an occlusive thrombosis of the superior vena cava and had her conventional VDD transvenous pacemaker replaced with a leadless device [45]. Limited venous access as an anatomical challenge may be overcome with a leadless pacemaker as in a case study of a bradycardic hemodialysis patient who suffered from skin erosion in the chest area due to radiation treatments for esophageal carcinoma. The leadless pacemaker was implanted successfully, but the patient developed ventricular tachyarrhythmias, necessitating the implantation of a subcutaneous implantable cardioverter-defibrillator. At 1 month, both devices were performing adequately with no device-device interactions [46].
A 72-year-old man with a thrombosed venous stent, renal failure, and myelodysplastic syndrome presented with second-degree AV block. A leadless pacemaker was preferred (Micra™) because of limited venous access and a high risk of infection due to his immunocompromised condition [47].
When it is necessary to extract transvenous leads in a pacemaker-dependent patient, a common approach is to utilize a temporary pacemaker with active-fixation lead as a bridge to a contralateral pacemaker implantation. A case report describes the use of a leadless pacemaker in a pacemaker-dependent patient with dextrocardia who required lead extraction following endocarditis. The implantation procedure was uneventful and the leadless pacemaker performed well with stable measurements taken 1 year postimplant [48].
The literature reports on successful implantation of a leadless pacemaker in a transplanted heart [49].
The permanent position of a transvenous lead over the tricuspid valve may cause damage to the valve. In patients with a prosthetic tricuspid valve, locating a transvenous lead over the tricuspid valve must be considered carefully. The literature reports a case in which a 67-year-old woman with three valve replacements (an aortic mechanical valve, a mitral mechanical valve, and a tricuspid prosthesis) underwent successful implantation of a leadless pacemaker (Micra™) for high-degree AV block with permanent atrial fibrillation. She had previously had an epicardial pacemaker, which experienced lead dysfunction and transient loss of capture [50].
In a study of 23 leadless pacemaker patients (both Micra™ and Nanostim™), devices were implanted in the septal-apical area or the mid-septal region of the right ventricle. No observed changes in heart structure or heart function, such as changes to the tricuspid valve, were found. One patient in this study developed increased tricuspid valve regurgitation but without abnormal leaflet motion or any changes in annulus size, suggesting it was caused by changes in right ventricular pressure [51].
It is not difficult to imagine the possibilities of combining a subcutaneous ICD (S-ICD) with a leadless pacemaker to allow for bradycardia pacing support and rescue defibrillation in a patient without the need for any transvenous leads. In an experimental study (n = 40, animal models were ovine, porcine, and canine), the dual devices were successfully implanted in 39/40 and 23 animals were followed for 90 days. Appropriate pacing was observed in 100% of animals by the leadless pacemaker, and the ICD could communicate unidirectionally with the pacemaker in 99% of cases. When triggered, the leadless pacemaker could deliver antitachycardia pacing (10 beats at 81% of the coupling interval) in 100% of attempts, while the S-ICD was able to maintain appropriate sensing [52]. While this is a preliminary animal study, it demonstrates the potential of utilizing these two leadless systems in tandem. For an S-ICD and a leadless pacemaker to work effectively together, they require the ability to communicate with each other, which, in turn, depends on the device orientation within the subject. In a canine study (n = 23), it was found that communication could occur in 100% of the implanted dogs although the median angle of the leadless pacemaker was 29°, and the median distance of the S-ICD to the leadless pacemaker was 0.8 cm. While these are not optimal values, communication was effective. A retrospective study of 72 leadless pacemaker patients found the median angle of the leadless pacemaker was 56 degrees; in a retrospective analysis of 100 S-ICD patients, the median distance between the coil and the position of the leadless pacemaker was 4.6 cm [53]. Thus, it appears that communication between devices is possible and that humans offer a better theoretical positioning opportunity for such communication than dogs.
Dual device implantation was performed in an 81-year-old man who received an S-ICD in 2012 after explant of three transvenous ICDs due to infection [54]. At the time of S-ICD implant, the patient had no indication for bradycardia pacing, but that changed in 2015 when he developed sinus bradycardia with a daytime heart rate of about 20 bpm. Both subclavian veins were occluded, and it was decided to implant a leadless pacemaker (Micra™). The device was successfully implanted with satisfactory electrical measurements (capture threshold was 0.38 V at 0.24 ms capture threshold, the R-wave was 10.4 mV, and impedance was 640 Ω). When programmed to high outputs, the leadless pacemaker did not appear to interact with the S-ICD, even at its most sensitive settings. The patient was doing well with improved function at 4 months. At 6 months, the patient had a VT that was appropriately sensed and converted at first shock. The threshold of the leadless pacemaker following the shock remained stable [54].
For patients with chronic renal disease, a leadless pacemaker may allow preservation for central veins, necessary for permanent dialysis vascular access [55]. In patients with end-stage renal disease and the need for an implantable pacemaker, it is best to avoid transvenous leads if possible. Since kidney disease can progress rapidly, patients with a high risk for renal failure (for example, glomerular filtration rate < 20 mL/min/1.73 m2); it may be helpful to consider these patients for leadless pacemakers or S-ICD systems rather than transvenous devices when possible [56].
Leadless pacemakers are contraindicated in patients with an indwelling inferior vena cava (IVC) filter, but as IVC filters become more common, the role of leadless pacemakers in this population will be explored. In some cases, an IVC filter might block passage of a catheter entering the femoral vein and routing toward the heart, but there are cases reported in the literature in which the catheter with the leadless pacemaker has been able to navigate around the indwelling IVC device. However, large studies of leadless pacemakers exclude IVC filter patients, so there is not much data on how a leadless pacemaker might be deployed in this population. A few cases in the literature suggest it is feasible, at least in selected cases, to implant a leadless pacemaker in the presence of an IVC filter.
A case report in the literature describes the successful implant of a Micra™ device via a collateral branch of the right common femoral vein through a previously implanted IVC filter in a 68-year-old man with a history of pulmonary embolism and recent development of AV block [57].
There is a report in the literature of a dual implant of a left-atrial-appendage occluder (Watchman™, Boston Scientific, Natick, Massachusetts, USA) and a leadless pacemaker (Micra™) in a single procedure. The patient was a 73-year-old woman with persistent atrial fibrillation. Both devices were implanted via right femoral access with no complications and good results at 1 month postimplant [58].
The idea that this miniaturized pacemaker might be appropriate in smaller patients has been explored in a few case studies. The literature reports a successful implantation of a leadless device (Micra™) in an 11-year-old patient with recurrent syncopal episodes and prolonged sinus pauses [59]. A 71-year-old man with achondroplastic dwarfism had a transvenous pacemaker for decades for third-degree AV block; in 2010, a pocket infection with endocarditis of the tricuspid valve necessitated the extraction of the conventional pacemaker and placement of an epicardial dual-chamber pacemaker with tunneling of leads. The patient was pacemaker dependent with permanent atrial fibrillation and developed an untreatable pocket infection. He was implanted with a leadless pacemaker (Micra™) via standard implantation technique, which was complicated by the fact that the delivery catheter was much longer than the patient’s inferior limb. The device was successfully implanted and showed good electrical results. The epicardial device was then removed via a mini-thoracotomy [60]. A leadless pacemaker (Micra™) could be successfully implanted in a small-frame geriatric patient with third-degree AV block and a history of pacemaker implantations and infections [61].
A leadless pacemaker was successfully implanted in a 17-year-old male patient with cardioinhibitory syncope. The patient had vasovagal syncope with episodes of bradycardia and drops in arterial blood pressure. An implantable loop recorder documented a pause of 9 s, whereupon he was implanted with the leadless pacemaker [62]. Cardioinhibitory syncope may be a temporary condition.
For rate control in patients with symptomatic atrial fibrillation (AF), atrioventricular (AV) nodal ablation with subsequent pacemaker implantation (the so-called “ablate and pace” procedure) is an established course of treatment. In a multicenter observational study of 127 such patients, 60 received a leadless pacemaker and 67 a conventional transvenous pacemaker. The primary efficacy endpoint of this study was acceptable sensing thresholds (R wave ≥5.0 mV and pacing threshold ≤2.0 V at 0.4 ms). Nearly all patients (95% in leadless and 97% in conventional groups) met the primary endpoint. Five early and one late minor adverse events occurred in the leadless pacemaker group and three early adverse events occurred in the conventional pacemaker group (not statistically significantly different). Thus, it appears that leadless pacemakers may be a viable option for “ablate and pace” patients [63]. In another study in a similar population, 21 patients with permanent atrial fibrillation underwent implantation of a leadless pacemaker (Micra™) followed by AV junctional ablation; these patients were followed over 12 months with no major device-related complications. Two patients in this study died over the course of the 12 month follow-up of noncardiac causes [64]. Short- and long-term outcomes of patients undergoing a simultaneous leadless pacemaker implantation were reported from an observational study of 137 patients (mean age 77.9 ± 10.5 years) in which 19.7% (n = 37) underwent simultaneous AV nodal ablation. The complication rate was 5.5% in patients who just had leadless pacemaker insertion and 11% in those who underwent both ablation and pacemaker implant. There were no cases of device dislodgement in either group. Over the mean follow-up of 123 ± 48 days, 3.6% patients (n = 3) died, but all deaths were unrelated to cardiovascular causes. There were no significant differences between groups in terms of pacing and sensing threshold values [65].
The literature reports on a 66-year-old female with rheumatic heart disease, permanent atrial fibrillation with slow ventricular response, and renal failure. She was admitted for mitral valve replacement and tricuspid valve repair, at which time a
The literature reports a case in which a 91-year-old man underwent a successful transcatheter aortic valve implantation (TAVI) but experienced the not uncommon side effect of conduction disturbances. As the patient was frail and elderly, it was decided to implant a leadless pacemaker to help manage the arrhythmias rather than a transvenous system. The procedure was successful and the patient was discharged without complications [67].
Patients with congenital heart disorders are at an elevated risk for arrhythmias and anatomical anomalies, which may complicate venous access and device implantation. In fact, congenital heart disease patients have a rate for pacemaker-related complications that approaches 40% compared to about 5% in the general population [68]. A case study in the literature reports on a 47-year-old female pacemaker-dependent patient with congenital heart disease who had experienced complications with a transvenous pacemaker (lead malfunction followed by occlusion of the superior vena cava and innominate veins). The transvenous lead was abandoned, and the patient was revised to an epicardial system. She presented with dizzy spells, and it was found her epicardial system was nearing end of service and had elevated thresholds. As there was no viable vascular access, it was decided to revise her pacemaker to a leadless system (Micra™). The leadless pacemaker was implanted via left femoral venous access and a steerable catheter to the right ventricular apical septal region where it was successfully positioned with good electrical values (1.0 V at 0.4 ms with an R-wave of 8 mV) [69].
At present, leadless pacemakers cost significantly more than a conventional transvenous device without the expense of two transvenous leads. The question of cost effectiveness in medical devices is always complicated, but it must be taken into account that even with a higher upfront cost, leadless pacemakers have substantially longer expected longevity (up to twice as long as a conventional transvenous pacemaker) and fewer complications [13]. In an online survey conducted by the European Heart Rhythm Association (EHRA) of 52 centers who participate in the EHRA Research Network, most of the 52 centers who reported said they implanted leadless pacemakers (86%) but at a small volume (82% said they implanted fewer than 30 such devices in the past 12 months). The main reasons for the low volume were device costs (91%) and lack of reimbursement for these systems (55%) [50].
Currently, leadless pacing is limited to right-ventricular pacing only. The vast majority of pacemaker patients depend on AV synchronization and may even benefit from additional cardiac resynchronization for heart failure. One way to solve the AV-sequential issue is to employ VDD mode that would allow for atrial sensing; a subcutaneous ECG integrated into the circuit would be an option.
Systems that are able to communicate between devices are being developed, i.e., integration of a leadless pacemaker with an S-ICD. Ideally, this combination would offer reliable sensing/pacing in the right ventricle including antitachycardia pacing in order to terminate VT without shock therapy. Moreover, combining intracardiac signals from the leadless pacemaker with the subcutaneous ECG from the S-ICD may improve the system’s ability to discriminate arrhythmias.
Another concern is handling of the device at the end of its service life. Likely, the devices will be encapsulated and could be programmed off (OOO mode), and up to three devices can reasonably be accommodated within the right ventricle [33]. However, many pacemaker patients are old with a shorter life expectancy than projected batter longevity and will only need one device.
Extraction will be necessary in the event of an infection, and the development of safe catheter-based tools would be helpful even in the situation of complete device encapsulation. More data are needed about safety of leadless pacemakers with regard to infection, device migration, and RV failure in long-term follow-up.
A leadless ultrasound-based technology used by the WiCS™ system (Wireless Cardiac Stimulation, EBR Systems) has been developed for endocardial pacing of the left ventricle [70]. The ultrasound energy is transmitted from a subcutaneous transmitter to an endocardial receiver unit in the endocardium. This device is fixed by three self-expanding nitinol tines on the device. Thus, this cardiac resynchronization therapy (CRT) system comprises three parts: the left-ventricular endocardial unit (using ultrasound for conversion of electrical energy), the subcutaneous pulse generator, and a conventional pacing device. The subcutaneously implanted pulse generator consists of a battery connected by a cable to a transmitter. The system detects right-ventricular stimulation provided by the concomitant pacemaker, CRT device, or ICD.
The technology of leadless pacing is a disruptive innovation with the potential to usher in a new era of cardiac pacing and solve problems related to the transvenous leads and pocket. The first-generation leadless pacemakers are limited to single-chamber pacing, typically VVIR pacing, but further innovations may expand that. Battery longevity is supposed to be excellent, but real-world clinical data are needed from long-term use to confirm this. The extraction of a leadless pacemaker remains a challenge. Future directions include integration of leadless pacing with S-ICDs, dual-chamber devices, and a leadless version of CRT pacing.
Todd Cooper of Coyote Studios in Los Angeles, California, provided the original illustration. The authors acknowledge editorial assistance provided by John Bisney who proofed the final manuscript. Trademarks and registered trademarks in this chapter are the property of their respective owners.
The authors have no relevant conflicts to disclose.
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Integrity - We are consistent and dependable, always striving for precision and accuracy in the true spirit of science.
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\n\nDisruptiveness - We are eager for discovery, for new ideas and for progression. We approach our work with creativity and determination, with a clear vision that drives us forward. We look beyond today and strive for a better tomorrow.
\n\nIntechOpen is a dynamic, vibrant company, where exceptional people are achieving great things. We offer a creative, dedicated, committed, and passionate environment but never lose sight of the fact that science and discovery is exciting and rewarding. We constantly strive to ensure that members of our community can work, travel, meet world-renowned researchers and grow their own career and develop their own experiences.
\n\nIf this sounds like a place that you would like to work, whether you are at the beginning of your career or are an experienced professional, we invite you to drop us a line and tell us why you could be the right person for IntechOpen.
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Viana",authors:[{id:"15565",title:"Prof.",name:"Julio",middleName:null,surname:"Viana",slug:"julio-viana",fullName:"Julio Viana"},{id:"238389",title:"Ph.D.",name:"Sílvia",middleName:null,surname:"Cruz",slug:"silvia-cruz",fullName:"Sílvia Cruz"},{id:"247716",title:"Prof.",name:"Luís",middleName:null,surname:"Rocha",slug:"luis-rocha",fullName:"Luís Rocha"}]}],mostDownloadedChaptersLast30Days:[{id:"70315",title:"Some Basic and Key Issues of Switched-Reluctance Machine Systems",slug:"some-basic-and-key-issues-of-switched-reluctance-machine-systems",totalDownloads:1238,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Although switched-reluctance machine (SRM) possesses many structural advantages and application potential, it is rather difficult to successfully control with high performance being comparable to other machines. Many critical affairs must be properly treated to obtain the improved operating characteristics. This chapter presents the basic and key technologies of switched-reluctance machine in motor and generator operations. The contents in this chapter include: (1) structures and governing equations of SRM; (2) some commonly used SRM converters; (3) estimation of key parameters and performance evaluation of SRM drive; (4) commutation scheme, current control scheme, and speed control scheme of SRM drive; (5) some commonly used front-end converters and their operation controls for SRM drive; (6) reversible and regenerative braking operation controls for SRM drive; (7) some tuning issues for SRM drive; (8) operation control and some tuning issues of switched-reluctance generators; and (9) experimental application exploration for SRM systems—(a) wind generator and microgrid and (b) EV SRM drive.",book:{id:"8899",slug:"modelling-and-control-of-switched-reluctance-machines",title:"Modelling and Control of Switched Reluctance Machines",fullTitle:"Modelling and Control of Switched Reluctance Machines"},signatures:"Chang-Ming Liaw, Min-Ze Lu, Ping-Hong Jhou and Kuan-Yu Chou",authors:[{id:"37616",title:"Prof.",name:"Chang-Ming",middleName:null,surname:"Liaw",slug:"chang-ming-liaw",fullName:"Chang-Ming Liaw"},{id:"306461",title:"Mr.",name:"Min-Ze",middleName:null,surname:"Lu",slug:"min-ze-lu",fullName:"Min-Ze Lu"},{id:"306463",title:"Mr.",name:"Ping-Hong",middleName:null,surname:"Jhou",slug:"ping-hong-jhou",fullName:"Ping-Hong Jhou"},{id:"306464",title:"Mr.",name:"Kuan-Yu",middleName:null,surname:"Chou",slug:"kuan-yu-chou",fullName:"Kuan-Yu Chou"}]},{id:"52822",title:"Non-Orthogonal Multiple Access (NOMA) for 5G Networks",slug:"non-orthogonal-multiple-access-noma-for-5g-networks",totalDownloads:14819,totalCrossrefCites:27,totalDimensionsCites:37,abstract:"In this chapter, we explore the concept of non-orthogonal multiple access (NOMA) scheme for the future radio access for 5G. We first provide the fundamentals of the technique for both downlink and uplink channels and then discuss optimizing the network capacity under fairness constraints. We further discuss the impacts of imperfect receivers on the performance of NOMA networks. Finally, we discuss the spectral efficiency (SE) of the networks that employ NOMA with its relations with energy efficiency (EE). We demonstrate that the networks with NOMA outperform other multiple access schemes in terms of sum capacity, EE and SE.",book:{id:"5480",slug:"towards-5g-wireless-networks-a-physical-layer-perspective",title:"Towards 5G Wireless Networks",fullTitle:"Towards 5G Wireless Networks - A Physical Layer Perspective"},signatures:"Refik Caglar Kizilirmak",authors:[{id:"188668",title:"Dr.",name:"Refik Caglar",middleName:null,surname:"Kizilirmak",slug:"refik-caglar-kizilirmak",fullName:"Refik Caglar Kizilirmak"}]},{id:"77871",title:"Protection of Microgrids",slug:"protection-of-microgrids",totalDownloads:279,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The concept of microgrids goes back to the early years of the electricity industry although the systems then were not formally called microgrids. Today, two types of microgrids can be seen: independent and grid connected. The protection requirement of these two types differs as the protection needs of an independent microgrid are intended for protecting components and systems within the microgrid, whereas a grid connected microgrid demands both internal and external protection. The first part of this chapter is dedicated to independent microgrids. How protection devices such as residual current circuit breakers, miniature and moulded case circuit breakers, and surge protective devices should be selected for an example microgrid is discussed while referring to the relevant standards. In the next section, the protection of a grid connected microgrid is discussed. Particularly, micro-source protection, microgrid protection, loss of mains protection and fault ride-through requirements are discussed while referring to two commonly used distributed generator connection codes. An example with simulations carried out in the IPSA simulation platform was used to explain different protection requirements and calculation procedures. Finally, grounding requirements are discussed while referring to different interfacing transformer connections and voltage source inverter connections.",book:{id:"10176",slug:"microgrids-and-local-energy-systems",title:"Microgrids and Local Energy Systems",fullTitle:"Microgrids and Local Energy Systems"},signatures:"Janaka Ekanayake",authors:[{id:"328170",title:"Prof.",name:"Janake",middleName:null,surname:"Ekanayake",slug:"janake-ekanayake",fullName:"Janake Ekanayake"}]},{id:"47585",title:"Free Space Optical Communications — Theory and Practices",slug:"free-space-optical-communications-theory-and-practices",totalDownloads:9023,totalCrossrefCites:43,totalDimensionsCites:57,abstract:null,book:{id:"4473",slug:"contemporary-issues-in-wireless-communications",title:"Contemporary Issues in Wireless Communications",fullTitle:"Contemporary Issues in Wireless Communications"},signatures:"Abdulsalam Ghalib Alkholidi and Khaleel Saeed Altowij",authors:[{id:"100466",title:"Dr.",name:"Abdulsalam",middleName:null,surname:"Alkholidi",slug:"abdulsalam-alkholidi",fullName:"Abdulsalam Alkholidi"},{id:"131091",title:"MSc.",name:"Khalil",middleName:null,surname:"Altowij",slug:"khalil-altowij",fullName:"Khalil Altowij"}]},{id:"41657",title:"Algorithms for Efficient Computation of Convolution",slug:"algorithms-for-efficient-computation-of-convolution",totalDownloads:10069,totalCrossrefCites:15,totalDimensionsCites:20,abstract:null,book:{id:"3158",slug:"design-and-architectures-for-digital-signal-processing",title:"Design and Architectures for Digital Signal Processing",fullTitle:"Design and Architectures for Digital Signal Processing"},signatures:"Karas Pavel and Svoboda David",authors:[{id:"154795",title:"Ph.D. Student",name:"Pavel",middleName:null,surname:"Karas",slug:"pavel-karas",fullName:"Pavel Karas"},{id:"155141",title:"Dr.",name:"David",middleName:null,surname:"Svoboda",slug:"david-svoboda",fullName:"David Svoboda"}]}],onlineFirstChaptersFilter:{topicId:"116",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82123",title:"Microwave-Assisted Pyrolysis Process: From a Laboratory Scale to an Industrial Plant",slug:"microwave-assisted-pyrolysis-process-from-a-laboratory-scale-to-an-industrial-plant",totalDownloads:4,totalDimensionsCites:0,doi:"10.5772/intechopen.104925",abstract:"One of the great challenges for the European Union (EU) is the “Circular Economy Package,” and to achieve this goal, materials at the end of their life cycle must be recycled using a sustainable process. In this way, as a thermochemical treatment, pyrolysis represents a significant opportunity so long it leads to the recovery of both energy and chemical content of mixed, contaminated, or deteriorated plastics. An excellent history of an academic-industrial adventure started in 2008 at the Department of Chemistry of the University of Florence demonstrates the possibility of employing microwaves to recycle plastics to preserve their energy and chemical content. After that, Techwave started industrialization of the process in 2019, realizing a small-scale prototype followed by a full-scale pilot plant using different plastic materials (e.g., polystyrene, acrylonitrile-butadiene-styrene (ABS), and polypropylene). Nowadays, the plant may process 90 kg/h of plastics with a low formation of char and gas and an interesting amount of liquid useful as a source of chemicals or fuel because it has an LHV of 35–43 kJ/kg. The Microwave-Assisted Pyrolysis (MAP) is an industrial novelty in plastic recycling, and it looks very promising for a much more modern and innovative plastic waste recovery system.",book:{id:"11145",title:"Recent Microwave Technologies",coverURL:"https://cdn.intechopen.com/books/images_new/11145.jpg"},signatures:"Marco Frediani, Piero Frediani, Gianni Innocenti, Irene Mellone, Roberto Simoni and Gianpaolo Oteri"},{id:"82420",title:"Applications of Microwaves in Medicine and Biology",slug:"applications-of-microwaves-in-medicine-and-biology",totalDownloads:7,totalDimensionsCites:0,doi:"10.5772/intechopen.105492",abstract:"This chapter deals with the description of recent research activities oriented on the perspective of microwave technologies in medicine and biology. It brings new ideas about the possibilities of using microwaves in thermotherapy—above all toward hyperthermia in cancer treatment. Development of new types of hyperthermia applicators (based, e.g., on technologies such as metamaterials, evanescent modes in waveguides, and other types of transmission structures) will be discussed here. Furthermore, we would like to underline in this chapter perspectives of microwaves in medical diagnostics. It is possible to expect that, e.g., microwave differential tomography, UWB radar, and microwave radiometers (all three can be used both for medical diagnostic and for noninvasive temperature measurement) will soon play an important role in it. Finally, experimental equipment necessary for research on the biological effects of EM fields is presented.",book:{id:"11145",title:"Recent Microwave Technologies",coverURL:"https://cdn.intechopen.com/books/images_new/11145.jpg"},signatures:"David Vrba, Jan Vrba, Ondrej Fiser, Jesus Cumana, Milan Babak and Jan Vrba Senior"},{id:"81917",title:"Fluidics for Reconfigurable Microwave Components",slug:"fluidics-for-reconfigurable-microwave-components",totalDownloads:11,totalDimensionsCites:0,doi:"10.5772/intechopen.104857",abstract:"Dielectric and conducting liquids with varying electromagnetic properties can offer novel alternatives for building tunable microwave passive components as well as antennas. Injecting these fluidics in or around microwave substrates alters their overall electrical characteristics, enabling circuit reconfigurability. Alternatively, changing the shapes and dimensions of conductors by using liquid metals can achieve similar reconfigurability. An overview of different liquids and their electromagnetic properties is first given. The principles behind the reconfigurability of the electrical characteristics of typical guiding structures based on mode shape variation in the presence of fluids are discussed. The realization of an N-bit programmable impedance tuner in 3D LTCC technology based on these principles is presented.",book:{id:"11145",title:"Recent Microwave Technologies",coverURL:"https://cdn.intechopen.com/books/images_new/11145.jpg"},signatures:"Dorra Bahloul, Ines Amor and Ammar Kouki"},{id:"82046",title:"One Model of Microwave Heating of Water Drop",slug:"one-model-of-microwave-heating-of-water-drop",totalDownloads:7,totalDimensionsCites:0,doi:"10.5772/intechopen.104949",abstract:"This work deals with the modeling of microwave heating of a water drop. A drop model is reduced to its electric dipoles, masses, and charges are constructed using the associating of COMSOL Multiphysics and Matlab software. The considered model proposes a microscopic point of view on microwave heating, which transforms electrical energy into heat.",book:{id:"11145",title:"Recent Microwave Technologies",coverURL:"https://cdn.intechopen.com/books/images_new/11145.jpg"},signatures:"Serge Lefeuvre and Olga Gomonova"},{id:"82076",title:"Power Divider/Combiner",slug:"power-divider-combiner",totalDownloads:13,totalDimensionsCites:0,doi:"10.5772/intechopen.104911",abstract:"With the remarkable progress in the use of Internet of Things (IoT) and 5G, there is a demand for higher performance such as miniaturization, broadband/multiband, low loss, and high integration for several microwave circuits. This chapter treats microwave power dividers/combiners used in amplifiers, mixers, phase shifters, antenna feeding networks, and so on. Here, the treated circuits are composed of LC-ladder circuits and an absorption resistor. It shows that multiband (dual-band and tri-band) and broadband can be achieved by changing the number of stages of the LC-ladder circuit. In addition, the effectiveness of this design method is demonstrated by electromagnetic simulations and prototype experiments.",book:{id:"11145",title:"Recent Microwave Technologies",coverURL:"https://cdn.intechopen.com/books/images_new/11145.jpg"},signatures:"Tadashi Kawai, Ayumu Tsuchiya and Akira Enokihara"},{id:"82035",title:"Orbital Angular Momentum Wave and Propagation",slug:"orbital-angular-momentum-wave-and-propagation",totalDownloads:33,totalDimensionsCites:0,doi:"10.5772/intechopen.104477",abstract:"Orbital angular momentum (OAM) techniques are exploited for a wide range of potential radiofrequency (RF) and electromagnetic applications, including megahertz-through-terahertz wireless systems, fiber-based and free-space optical communications and sensing, just like acoustic and any other wave-based counterparts. In those RF and electromagnetic applications, OAM wave is set to enable the development of high-speed and high-capacity communications, radar imaging, and sensing systems, among many others. In this chapter, a comprehensive comparison between plane wave and OAM wave propagation using a patch antenna as a radiator at 2.45 GHz is presented and discussed. This comparison allows the appreciation of the fundamental properties of the OAM wave when compared against its plane wave counterpart. For simplified comparison and discussion, we will use two abbreviated terms: PWPA for plane-wave patch antenna and OWPA for OAM wave patch antenna. PWPA refers to as planar patch antenna that produces plane waves in far-field, whereas patch antenna that delivers OAM waves in far-field is termed as OWPA. In this context, all physical quantities for wave propagation such as electric field, magnetic field, wave impedance, wave vector, velocity, pitch, and propagation constant are theoretically studied for OAM waves and compared with plane waves. First, OAM wave generation is studied through widely used uniform circular antenna array (UCAA) in literature. Then, plane wave patch antenna (PWPA) and OAM wave patch antenna (OWPA) are designed and verified through simulation and measurement. OWPA is designed with characteristic mode analysis (CMA) based on a lossy substrate to excite a twisting wave at a determined patch location. With this in mind, a comparative investigation of PWPA and OWPA is conducted for different physical parameters. Cylindrical near-field scan clearly shows a helical wave motion for OWPA, whereas a normal plane wave motion for PWPA. Furthermore, the comparison of plane wave and OAM wave propagation is demonstrated using the combination of a Tx–Rx antenna pair. It is observed that the overall signal from OWPA can be received with two PWPAs at an angle as OWPA has a dispersive beam. Moreover, the receiving antenna with a large aperture and plane wave horn antenna (PWHA) in the line of sight (LOS) range can also be used to receive the overall signal from OWPA. The received signal in PWPA–PWPA, OWPA–OWPA, OWPA–PWPA–PWPA, OWPA–PWHA Tx–Rx pairs is thoroughly compared and studied. Measured and simulated results for transmission are −30 dB for 0 dB input signal in OWPA–PWPA–PWPA and OWPA–PWHA cases, which are reasonably justified within the sensitivity/dynamic range of short-distance communication and radar sensing receivers.",book:{id:"11145",title:"Recent Microwave Technologies",coverURL:"https://cdn.intechopen.com/books/images_new/11145.jpg"},signatures:"Pankaj Jha and Ke Wu"}],onlineFirstChaptersTotal:14},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:106,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:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,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:"June 29th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:32,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. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. 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. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). 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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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:"June 29th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:318,numberOfPublishedBooks:32,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"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"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",fullName:"Abdulsamed Kükürt",profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",institutionString:null,institution:{name:"Kafkas University",institutionURL:null,country:{name:"Turkey"}}},{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/100644",hash:"",query:{},params:{id:"100644"},fullPath:"/profiles/100644",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()