UWB radio-over-fibre parameters employed in the setup in Fig. 14.
\r\n\tThis book will aim at serving as a complete and updated reference for a broad audience, including, students, orthotics, optometrist and ophthalmologist. The book will describe in detail general myopia features as well the most recent diagnostic techniques (e.g. OCT and visual field) which occupy a more and more relevant position in early myopia complications detection. It will explore the connection between myopia and other, popular disorders such as glaucoma, choroidal neovascularization, and retinal detachment: highly myopic eyes tend to have a retina and choroid thinner than normal and, then, the assessment of myopic eyes is far from being a simple task even with the most advanced imaging techniques. In the light of such observations, the book will give a special mention to pharmacological and surgical treatments currently available along with rehabilitation procedures and optical devices.
",isbn:null,printIsbn:"979-953-307-X-X",pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"41ca0f616bfa2745783b652b87ebedc3",bookSignature:"Prof. Felicia M. Ferreri",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/8705.jpg",keywords:"Myopia of prematurity, Retinal detachment, Intraocular pressure, Myopia and glaucoma, Myopic macular degeneration, Ocular motility,Visual rehabilitation, Clinical treatment, Retinal sensitivity, Visual Electrophysiology response, Visual Field, Ultrasonic Biometry",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"December 3rd 2018",dateEndSecondStepPublish:"December 24th 2018",dateEndThirdStepPublish:"February 22nd 2019",dateEndFourthStepPublish:"May 13th 2019",dateEndFifthStepPublish:"July 12th 2019",remainingDaysToSecondStep:"2 years",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"32442",title:"Prof.",name:"Felicia M.",middleName:null,surname:"Ferreri",slug:"felicia-m.-ferreri",fullName:"Felicia M. Ferreri",profilePictureURL:"https://mts.intechopen.com/storage/users/32442/images/system/32442.png",biography:"Felicia M. Ferreri graduated summa cum laude from University of Messina, Italy in 1998 and completed her ophthalmology residency at the Policlinico Universitario, Messina in 2002. She was interned at San Raffaele Hospital in Milan (Corneal Section) and at Hospital Careggi in Florence (pediatric ophthalmology diseases). She spent research periods in Seville ('Virginio del Rocio' hospital), Madrid ('San Carlos' hospital), Manchester ('The 'Bolton Hospital') and Rio de Janiero (Universidade Fluminense).\r\nShe served as co-investigator for many national and international clinical trials. Since 2002, she is an Assistant Professor in Ophthalmology at the University of Messina. Her research interests are in the areas of glaucoma, neuro-ophthalmology, pediatric ophthalmology, and cataract. She authored more than 50 scientific papers.",institutionString:"University of Messina",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"University of Messina",institutionURL:null,country:{name:"Italy"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"191",title:"Ophthalmology",slug:"medicine-ophthalmology"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"280415",firstName:"Josip",lastName:"Knapic",middleName:null,title:"Mr.",imageUrl:"https://mts.intechopen.com/storage/users/280415/images/8050_n.jpg",email:"josip@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copy-editing and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"6786",title:"Optic Nerve",subtitle:null,isOpenForSubmission:!1,hash:"b21864e6a0b3b316480d18efda1e18ee",slug:"optic-nerve",bookSignature:"Felicia M. Ferreri",coverURL:"https://cdn.intechopen.com/books/images_new/6786.jpg",editedByType:"Edited by",editors:[{id:"32442",title:"Prof.",name:"Felicia M.",surname:"Ferreri",slug:"felicia-m.-ferreri",fullName:"Felicia M. Ferreri"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8855",title:"Retinoblastoma",subtitle:"Past, Present and Future",isOpenForSubmission:!1,hash:"1686b2f1d697de9d4bc2005a5fa9b998",slug:"retinoblastoma-past-present-and-future",bookSignature:"Hind Manaa Alkatan",coverURL:"https://cdn.intechopen.com/books/images_new/8855.jpg",editedByType:"Edited by",editors:[{id:"223782",title:"Dr.",name:"Hind",surname:"Alkatan",slug:"hind-alkatan",fullName:"Hind Alkatan"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6372",title:"Early Events in Diabetic Retinopathy and Intervention Strategies",subtitle:null,isOpenForSubmission:!1,hash:"46ff48bdb1bac8a69372566fff0e2f6d",slug:"early-events-in-diabetic-retinopathy-and-intervention-strategies",bookSignature:"Andrew T.C. Tsin and Jeffery G. Grigsby",coverURL:"https://cdn.intechopen.com/books/images_new/6372.jpg",editedByType:"Edited by",editors:[{id:"83501",title:"Dr.",name:"Andrew",surname:"Tsin",slug:"andrew-tsin",fullName:"Andrew Tsin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7858",title:"A Practical Guide to Clinical Application of OCT in Ophthalmology",subtitle:null,isOpenForSubmission:!1,hash:"8e2d479cc9258dee430f8ba4c353c468",slug:"a-practical-guide-to-clinical-application-of-oct-in-ophthalmology",bookSignature:"Michele Lanza",coverURL:"https://cdn.intechopen.com/books/images_new/7858.jpg",editedByType:"Edited by",editors:[{id:"240088",title:"Prof.",name:"Michele",surname:"Lanza",slug:"michele-lanza",fullName:"Michele Lanza"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8418",title:"Eye Motility",subtitle:null,isOpenForSubmission:!1,hash:"6f554b86583b2290b7dc0ae067e1d577",slug:"eye-motility",bookSignature:"Ivana Mravicic",coverURL:"https://cdn.intechopen.com/books/images_new/8418.jpg",editedByType:"Edited by",editors:[{id:"96701",title:"Dr.",name:"Ivana",surname:"Mravicic",slug:"ivana-mravicic",fullName:"Ivana Mravicic"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5917",title:"Causes and Coping with Visual Impairment and Blindness",subtitle:null,isOpenForSubmission:!1,hash:"59fe032e3de5e150eab8bf47bd2d8fdd",slug:"causes-and-coping-with-visual-impairment-and-blindness",bookSignature:"Shimon Rumelt",coverURL:"https://cdn.intechopen.com/books/images_new/5917.jpg",editedByType:"Edited by",editors:[{id:"54335",title:"Dr.",name:"Shimon",surname:"Rumelt",slug:"shimon-rumelt",fullName:"Shimon Rumelt"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7703",title:"Ocular Surface Diseases",subtitle:"Some Current Date on Tear Film Problem and Keratoconic Diagnosis",isOpenForSubmission:!1,hash:"3dcf967eb2f185930ce7fb7ae462d4e0",slug:"ocular-surface-diseases-some-current-date-on-tear-film-problem-and-keratoconic-diagnosis",bookSignature:"Dorota Kopacz",coverURL:"https://cdn.intechopen.com/books/images_new/7703.jpg",editedByType:"Edited by",editors:[{id:"271261",title:"Dr.",name:"Dorota",surname:"Kopacz",slug:"dorota-kopacz",fullName:"Dorota Kopacz"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7176",title:"Visual Impairment and Blindness",subtitle:"What We Know and What We Have to Know",isOpenForSubmission:!1,hash:"6b1848a23af744fba1f0eef95fb4b2d1",slug:"visual-impairment-and-blindness-what-we-know-and-what-we-have-to-know",bookSignature:"Giuseppe Lo Giudice and Angel Catalá",coverURL:"https://cdn.intechopen.com/books/images_new/7176.jpg",editedByType:"Edited by",editors:[{id:"87607",title:"M.D.",name:"Giuseppe",surname:"Lo Giudice",slug:"giuseppe-lo-giudice",fullName:"Giuseppe Lo Giudice"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6251",title:"Difficulties in Cataract Surgery",subtitle:null,isOpenForSubmission:!1,hash:"16adb188451fd4f0e63c07ffa24b2b14",slug:"difficulties-in-cataract-surgery",bookSignature:"Artashes Zilfyan",coverURL:"https://cdn.intechopen.com/books/images_new/6251.jpg",editedByType:"Edited by",editors:[{id:"157235",title:"Dr.",name:"Artashes",surname:"Zilfyan",slug:"artashes-zilfyan",fullName:"Artashes Zilfyan"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"8432",title:"Radio-over-Fibre Techniques and Performance",doi:"10.5772/39559",slug:"radio-over-fibre-techniques-and-performance",body:'\n\t\tRadio-over-fibre (RoF) techniques have been subject of research during the last decades and find application in optical signal processing (photonic analogue-to-digital converters, photonic-microwave filters, arbitrary waveform generation), antenna array beamforming, millimetre-wave and THz generation systems, or photonic up- and down-converting links for applications such as broadband wireless access networks, electronic warfare and RADAR processing, imaging and spectroscopy or radio-astronomy (Seeds & Williams, 2006; Capmany & Novak, 2007). In these applications a radio signal typically in the millimetre-wave band is transmitted through optical fibre employing laser sources and electro-optical devices.
\n\t\t\tThe use of optical fibre links to distribute telecommunication standards is the more successful application of RoF technology, usually known as hybrid fibre-radio (HFR) networks (Jager & Stohr, 2001). HFR networks have been deployed in the last decade due to the increasing demand of high-bitrate communication services in today’s access network. This demand is based on the steady market introduction of services requiring the transmission of massive data quantities, like high-definition movie distribution, on-line gaming and rich Internet experience by example (Merill Lynch, 2007).
\n\t\t\tThe HFR concept applied to the enhancements of community antenna television (CATV) networks reflected in the so-called hybrid-fibre coax (HFC) network, in which a combination of digital and analogue channels is distributed from a central location to many users distributed geographically (Darcie & Bodeep, 1990; Wilson et al., 1995). In HFC networks the last mile connection is provided through coaxial cable whilst in HFR networks the last mile connection is always a wireless link. This is not a minor difference, as the wireless environment is much more hostile than cable imposing restrictive RoF link performance requirements in terms of linearity, noise and power handling capabilities, key parameters to guarantee a spurious free dynamic range (SFDR) for the whole link high enough to cope with geographical dispersion of users and complex modulation formats used by current wireless standards. A simplified schematic of a HFR network is shown in Fig. 1.
\n\t\t\tRoF technology allows centralising the required RF signal processing functions in one shared location (Central Office, CO) and then to use optical fibre to distribute the RF signals to the remote access units (RAU). This allows important cost savings as the RAUs can be simplified significantly, as they only need to perform optoelectronic conversion and filtering and amplification functions. It is possible to use wavelength multiplexing techniques (WDM) in order to increase capacity and to implement advanced network features such as dynamic allocation of resources. This centralised and simplified RAU scheme allows lower cost system operation and maintenance, which are reflected into major system OPEX savings, especially in broadband wireless communication systems where a high density of RAUs is necessary.
\n\t\t\tSimplified schematic of a RoF system. LD: Laser diode. BS: Base Station. RAU: Remote Access Unit. BPF: Band-pass filter. Amp: Electrical amplifier.
The CO and the RAU perform electro-optical (E/O) and opto-electronic (O/E) conversion of wireless signals respectively. E/O conversion is achieved employing either directly modulated laser sources or external electro-optic modulators. O/E conversion is done employing photodetectors or photoreceivers (Seeds & Williams, 2006). Regarding the RF transport, when the signal is transported directly at the frequency of operation there are benefits regarding cost, complexity and upgradeability, as there is no need for complex RF signal processing at the RAU involving up/down conversion or base-band mux/demux (Capmany & Novak, 2007; Jager & Stohr, 2001).
\n\t\t\tRoF techniques and complete transmission systems have been demonstrated for frequencies up to 120 GHz (Hirata et al., 2003). As mentioned before, the most successful application of RoF technologies has been the transmission of wireless standards over optical fibre links in centralized architectures, also known as distributed antenna systems (DAS) for both indoor and outdoor applications. The broad bandwidth of the optical fibre facilitates standard- independent multiservice operation for cellular systems, such as GSM (Owaga et al., 1992), UMTS (Persson et al., 2006), wireless LAN (WiFi 802.11 a/b/g/n) (Chia et al., 2003; Niiho et al., 2004; Nkansah et al., 2006) and also for emerging technologies WiMAX (Pfrommer et al., 2006) and Ultra-wideband (UWB) (Llorente et al., 2007). Available commercial systems however are typically limited to frequency ranges between 800-2500 MHz. Demonstrations of such DAS systems include their deployment to provide uniform wireless coverage in important sportive events such as the 2000 Olympic games and 2006 world cup (Rivas & Lopes, 1998; Cassini & Faccin, 2003). For indoor applications where picocell configurations are envisaged, advanced multi-function devices such as waveguide electro-absorption modulator (Wake et al., 1997) or polarization independent asymmetric Fabry-Perot modulators (Liu et al., 2003; Liu et al., 2007) are used as detector/modulator.
\n\t\t\tTwo key factors limiting the overall transmission performance in RoF systems are the optical source and the electro-optic modulation technique employed. Regarding the laser source, at frequencies used for major wireless standards (GSM, WiFi 802.11 a/b/g, UMTS) and also WiMAX up to 5-6 GHz, directly modulated semiconductor lasers are preferred due to lower cost (Qian et al., 2005). For higher frequencies, the required performances can be satisfied only by externally modulated transmitters. Devices with bandwidth handling capabilities in excess of these required by near-term WIMAX deployments, in particular distributed feedback (DFB) lasers offering the required bandwidth and performances, exist commercially, but normally at a high cost taking into account the number of devices required for typical applications. Recently, a lot of research efforts have been devoted to the development of low-cost/high-performance transmitters, for instance uncooled lasers (Ingham et al., 2003; Hartmann et al., 2003) or vertical-cavity surface-emitting lasers (VCSEL) (Persson et al., 2006; Chia et al., 2003). Probably, the most restrictive requirement for wireless services provision over RoF systems is the SFDR. Nowadays SFDRs in excess of 100 dB Hz2/3 have been demonstrated experimentally, providing enough dynamic range to be employed in real applications (Seeds & Williams, 2006).
\n\t\tThe basic elements of RoF systems are broadband laser sources either employing direct or external modulation, a suitable transmission media such as multi-mode fibre (MMF), single-mode fibre (SMF) or plastic optical fibre (POF), and broadband photodetectors or photoreceivers (Seeds & Williams, 2006; Capmany & Novak, 2007; Dagli, 1999). The laser source and modulation method is the key element in the performance of RoF applications.
\n\t\t\t\tThe generation of the optical signal to be transmitted in the RoF system is of special difficulty in the case of UWB signals. UWB is a radio technology intended for cable replacement in home applications within a range of tens of meters (picocell range), with high-definition video and audio communications a potential application (Duan et al., 2006). UWB is also attractive in many other applications including medicine, sensor networks, etc. UWB radio offers: High data rate capability (>1 Gbit/s), low radiated power spectral density (PSD) minimising the interference, low-cost equipment commercially available. UWB is available in two main implementations: Multi-band orthogonal frequency-division multiplexing (MB-OFDM) and impulse radio. The ECMA standard (ECMA-368, 2007) uses MB-OFDM in 528 MHz individual sub-bands, whilst the impulse-radio implementation employs short pulses (in the range of hundreds of picoseconds) modulated in amplitude, time, polarity or shape to fill a desired bandwidth. MB-OFDM generally shows superior performance to the impulse-radio approach in terms of multi-path fading and intersymbol interference (ISI) tolerance, whilst impulse-radio is able to provide simultaneously communications, localization and ranging to a sub-centimetre resolution.
\n\t\t\t\tCurrently, UWB uses the unlicensed band from 3.1 to 10.6 GHz mainly for indoor communications (FCC 04-285, 2004; ECMA-368, 2007) and the 24 GHz band for vehicular short-range radar applications (SARA Group, 2009), with a bandwidth larger than 20% of the centre frequency or a 10-dB bandwidth of at least 500 MHz as in FCC regulation (FCC 04-285, 2004) or at least 50 MHz as in ETSI regulations (ETSI, 2008) and a maximum radiated PSD of -41.3 dBm/MHz to guarantee spectral coexistence with other wireless narrowband services complementary in terms of range and bitrate such as WiMAX. Nevertheless, the whole UWB band 3.1-10.6 GHz is not available worldwide due to coexistence concerns (WiMedia, 2009). Outside the United States, available effective bandwidth is 1.5 GHz which only supports hundreds of Mbit/s. However, the unlicensed 60 GHz band enables UWB multi-Gbit/s wireless communications worldwide, as shown in Fig. 2, while challenges related to wireless channel and transceiver design have to be addressed (Daniels & Heath, 2007).
\n\t\t\t\tInternational frequency allocations in the 60 GHz band (as of January 2009). (*) (ECC, 2009).
RoF distribution of UWB signals, termed UWB-over-fibre, has received great interest to extend the UWB range exploiting the advantages of the broad bandwidth, low loss, light weight, and immunity to electromagnetic interference offered by optical fibres.
\n\t\t\t\tIn this section, different techniques for generating impulse-radio UWB signals in the optical domain is reported, featuring frequencies ranging from baseband up to millimetre-wave bands, including 24 GHz and 60 GHz. Some laser source characteristics are also discussed.
\n\t\t\t\tFor UWB-over-fibre systems, it is desirable to generate UWB signals directly in the optical domain, avoiding the use of additional E/O and O/E conversions and exploiting the advantages provided by optics such as broadband processing, light weight, small size, and immunity to electromagnetic interference. Many techniques have been proposed to generate impulse-radio UWB signals in the 3.1-10.6 GHz band in the optical domain. These techniques have mainly focused on generating Gaussian monocycle and doublet pulse shapes, which have been demonstrated to provide better bit error rate (BER) and multipath performance among different pulse types (Chen & Kiaei, 2002).
\n\t\t\t\t\tRoF distribution of UWB signals in the band from 3.1 to 10.6 GHz for high-definition audio/video broadcasting in optical access networks, e.g. in fibre-to-the-home (FTTH) networks has been proposed (Llorente et al., 2008). The performance of both MB-OFDM and impulse-radio UWB implementations at 1.25 Gbit/s is experimentally analysed and compared for different SMF links, ranging from 25 km up to 60 km. Both UWB implementations exhibit error-free operation (BER< 10-9) up to 50 km without dispersion compensation. The impulse radio technology exhibits degraded performance compared with OFDM although other optimized impulse-radio generation and detection schemes could lead to different results. OFDM-UWB degrades quickly with fibre length, due to the carrier suppression effect (Schmuck, 1995).
\n\t\t\t\t\tSeveral demonstrations on optical generation of impulse-radio UWB in the band from 3.1 to 10.6 GHz including fibre and/or wireless transmission have been reported achieving 65 cm wireless distance at 500 Mbps data employing on-off keying (OOK) amplitude modulation (Abtahi et al., 2008); 20 cm at 1.025 Gbit/s OOK-modulated data after up to 10 km of dispersion-compensated SMF (Hanawa et al., 2009); 5 cm at 1.6875 Gbit/s OOK-modulated data after 24 km of SMF (Pan & Yao, 2009a); at 1.625 Gbit/s data employing pulse-position modulation (PPM) after up to 200 m of SMF (Shams et al., 2009a), or 37 km of SMF with no wireless transmission (Shams et al., 2009b); and at 781.25 Mbit/s data employing binary phase-shift keying (BPSK) modulation after 30 km of SMF (Yu et al., 2009). In addition, techniques have been reported capable of pulse shape modulation (PSM) (Dong et al., 2009), or reconfigurable for multiple modulation formats (Pan & Yao, 2009b).
\n\t\t\t\t\tPhotonic generation of Gaussian monocycle pulses based on balanced photodetection of data Gaussian pulses has been proposed (Hanawa et al., 2007; Beltrán et al., 2008). Data Gaussian pulses are first generated by intensity modulation of an electrical data sequence with optical Gaussian pulses from a pulsed laser. This technique is shown in Fig. 3.
\n\t\t\t\t\tGaussian monocycle pulse generation based on balanced photodetection. ODL: Optical delay line. BPD: Balanced photodetector. PD: Photodetector.
Monocycle pulses generated employing the technique in Fig. 3; (a) the temporal waveform and (b) its spectrum (resolution bandwidth: 30 kHz).
Optical data pulses are split into two equal parts to drive the two inputs of the balanced photodetector. Optical delay is employed to adjust the relative time delay between the two signals. The pulse width of Gaussian pulses and the time-delay difference are adjusted so as to generate the desired UWB bandwidth. This approach has been experimentally demonstrated employing an actively mode-locked fibre laser and a Mach-Zehnder modulator (MZM) (Beltrán et al., 2008). To control the pulse width, a spool of standard SMF is included after the MZM. Fig. 4 shows monocycles generated based on balanced photodetection exhibiting a UWB 10-dB bandwidth of 6 GHz at 1.25 Gbit/s.
\n\t\t\t\t\tGaussian monocycle pulses can also be generated based on differential photoreception of data Gaussian pulses (Beltrán et al., 2009b) targeting to reduce cost and complexity. Fig. 5 shows this technique. Again, data Gaussian pulses are first generated by intensity modulation of an electrical data sequence with optical Gaussian pulses from a pulsed laser. Optical data pulses are photodetected and amplified by an electrical amplifier providing complementary outputs. The two outputs are combined after adjusting their relative time delay to generate monocycles. The pulse width of Gaussian pulses and the time-delay difference are adjusted so as to generate the desired UWB bandwidth. This approach has been experimentally demonstrated employing an actively mode-locked fibre laser and a MZM.
\n\t\t\t\t\tGaussian monocycle pulse generation based on differential photoreceiver. PD: Photodetector. TIA: Transimpedance amplifier. EDL: Electrical Delay Line.
Monocycle pulses generated employing the technique in Fig. 5; (a) the temporal waveform and (b) its spectrum (resolution bandwidth: 300 kHz).
To control the pulsewidth, a spool of standard SMF is included after the MZM. Fig. 6 shows monocycles generated based on differential photoreception exhibiting a UWB 10-dB bandwidth of 3.8 GHz at 1.244 Gbit/s.
\n\t\t\t\t\tThe photonic techniques for Gaussian monocycle generation shown in Fig. 3 and Fig. 5 are capable of providing high-quality pulses covering the whole UWB band with simple and flexible configuration compared with other techniques employing custom fibre Bragg gratings, nonlinear optical processes or spectrum shaping components.
\n\t\t\t\t\tUWB generation requires a pulse width in the order of hundreds of picoseconds to generate a suitable UWB bandwidth and a multi-gigahertz pulse repetition rate equal to the target data rate of the system. Gain-switched laser diodes, as used in (Hanawa et al., 2007; Kaszubowska-Anandarajah et al., 2008), passive or active mode-locked fibre lasers, e.g. (PriTel, 2009), and emerging optically pumped passively mode-locked vertical-external-cavity surface-emitting lasers (VECSEL) can provide repetition rates suitable for UWB systems. In contrast to mode-locked lasers, gain switched lasers are simpler and more compact. However, timing jitter and also fluctuations of other pulse parameters are larger than for mode-locked lasers. Optically pumped VECSELs have the potential for very compact and cheap. In addition, suitable pulses for UWB applications could also be generated by modulating a continuous-wave light source, e.g. (Wu et al., 2007).
\n\t\t\t\tFor UWB optical transmission in RoF operating in the millimetre-wave bands, 24 GHz and 60 GHz, broadband optical frequency up-conversion centralized in the CO appears as a cost-effective solution instead of employing broadband electrical mixing at each RAU. A number of techniques have been reported for millimetre-wave impulse-radio UWB signal generation based on optical up-conversion. These techniques have been demonstrated in the 24 GHz band regulated for vehicular radar and also used in communications. One approach (Kuri et al., 2006) up-converts electrical rectangular pulses based on a complex self-heterodyne technique employing an arrayed waveguide grating (AWG) and a special MZM with high extinction ratio to suppress the residual RF carrier to meet the UWB emission mask. Another approach (Guennec & Gary, 2007) up-converts monocycle or doublet pulses generated by electrical transmitters commercially available by modulation in a MZM biased in nonlinear regime. This technique is simple, however it requires high-frequency electro-optic devices which make it difficult to be upgraded to higher frequency bands. The approaches demonstrated in (Fu et al., 2008; Li et al., 2009) serve as both frequency up-conversion and optical amplification and up-convert monocycle pulses generated employing electrical Gaussian pulses and a frequency discriminator. The former method is based on nonlinear polarization rotation in a semiconductor optical amplifier (SOA) exhibiting limited performance at high frequencies, whilst the latter method employs a more complex architecture based on a fibre optical parametric amplifier (OPA) but can be extended to higher frequency bands. An approach based on up-conversion of optical pulses in a MZM biased in non-linear regime has also been demonstrated (Chang et al., 2008). Optical monocycle and doublet pulses are generated by driving a dual-parallel MZM with electrical Gaussian pulses. In this demonstration, the performance of the millimetre-wave UWB signal after fibre transmission is analyzed showing the doublet pulse has better tolerance to fibre dispersion than the monocycle pulse.
\n\t\t\t\t\tGaussian monocycle pulses do not meet the FCC spectrum mask in the 3.1-10.6 GHz band. However, these pulses have been demonstrated to be suitable for further frequency up-conversion (Guennec & Gary, 2007). Optical up-conversion to 20 GHz of the generated baseband monocycles shown in Fig. 4 based on the technique in (Guennec & Gary, 2007) was also demonstrated in (Beltrán et al., 2008). A simpler approach to generate UWB monocycles in the millimetre-wave band based on frequency up-conversion of data Gaussian optical pulses in a MZM at the CO and monocycle shaping at RAUs has been proposed (Beltrán et al., 2009a; Beltrán et al., 2009c). This technique is depicted in Fig. 7.
\n\t\t\t\t\tMillimetre-wave impulse-radio UWB-over-fibre based on up-conversion in a Mach-Zehnder modulator at the CO and monocycle shaping at the RAU. LO: Local oscillator.
This method has been demonstrated in two proof-of-concept experiments by modulating Gaussian optical pulses from an actively mode-locked fibre laser with data in a MZM to generate data Gaussian pulses whose pulse width is subsequently controlled by standard SMF. A second MZM driven by a local oscillator (LO) signal and biased at quadrature point (linear regime) generating an optical double-sideband signal with carrier is employed for up-conversion. The millimetre-wave signal is so obtained after photodetection and filtering at the RAU. In order to verify appropriate operation, the millimetre-wave signal is down-converted with the same LO signal employed for up-conversion in an electrical mixer (conventional homodyne detection) and further low-pass filtered, with no fibre and no air transmission.
\n\t\t\t\t\tIn the first experiment (Beltrán et al., 2009a), monocycle shaping is based on balanced photodetection as shown in Fig. 3. UWB monocycles are generated at 19 GHz, exhibiting a single-sideband 10-dB bandwidth of 2.5 GHz at 622 Mbit/s, as shown in Fig. 8.
\n\t\t\t\t\ta) RF spectrum of UWB monocycles at 19 GHz generated in the setup in Fig. 1 with monocycle shaping as in Fig. 3. The FCC UWB mask is shown as a dashed line translated to 19 GHz; (b) down-converted data monocycles.
Also shown in Fig. 8 is the down-converted signal. The monocycles bear OOK-modulated data so that they are suitable for simultaneous vehicular radar and communications in the 24 GHz band to provide traffic safety applications.
\n\t\t\t\t\tMonocycle shaping based on differential photoreception as shown in Fig. 5 is performed in the second experiment (Beltrán et al., 2009c). This technique does not increase significantly the complexity of RAUs. UWB monocycles are generated at 16.85 GHz, exhibiting a single-sideband 10-dB bandwidth of 2.5 GHz and bearing OOK-modulated data at 1.244 Gbit/s, as shown in Fig. 9. Also shown in Fig. 9 is the down-converted signal.
\n\t\t\t\t\ta) RF spectrum of UWB monocycles at 16.85 GHz generated in the setup in Fig. 7 with monocycle shaping as in Fig. 5. The FCC UWB mask is shown as a dashed line translated to 16.85 GHz; (b) eye diagram of down-converted data monocycles.
As can be observed in Fig. 8 and Fig. 9, the RF residual carrier does not limit the UWB emission mask. This enables the simultaneous wireless transmission of the two spectral sidebands improving receiver sensitivity at expense of reduced spectral efficiency. The two sidebands could be also filtered separately enabling a simultaneous dual-band generation.
\n\t\t\t\t\t\n\t\t\t\t\t\tFig. 10 shows a UWB-over-fibre system where optical data monocycles are frequency up-converted in a MZM in nonlinear regime. This approach has been proposed and demonstrated in a proof-of-concept experiment for millimetre-wave UWB generation in the 60 GHz band (Beltrán et al., 2009b). Electrical Gaussian monocycles are converted to optical domain by external modulation in a MZM to generate optical data monocycles. In the experiment, electrical OOK-modulated monocycles are generated as shown in Fig. 5. Fig. 11 (a) shows the so-obtained optical data monocycles. A low-frequency LO of 14.25 GHz multiplied by 2 is applied to a second MZM biased at minimum transmission point to generate an optical double-sideband signal with a suppressed carrier (optical carrier suppression modulation), resulting in UWB monocycles at 57 GHz after photodetection and filtering at the RAU. The millimetre-wave signal is down-converted by electrical homodyne detection employing the LO signal multiplied by 4 and further low-pass filtered to verify appropriate operation, with no air transmission.
\n\t\t\t\t\tUWB monocycles are generated at 57 GHz, exhibiting a 10-dB bandwidth of 3.8 GHz at 1.244 Gbit/s, as shown in Fig. 11 (b). In this technique it is required to filter the residual RF carrier frequency for wireless transmission in practice. Further transmission over 100 m of standard SMF is demonstrated with no performance degradation. Fig. 11 (c) shows the demodulated signal after fibre transmission. This UWB RoF system has been proposed for multi-Gbit/s high-definition video/audio distribution within in-vehicle networks, e.g. in aircrafts, where also fibre interconnects RAUs along the vehicle. The impulse-radio UWB approach offers also ranging and localization functionalities of special interest for localization of users potentially interfering and for radio tagging and passenger identification applications.
\n\t\t\t\t\tSetup of the photonic 60 GHz impulse UWB-over-fibre based on up-conversion of data optical monocycles in a Mach-Zehnder modulator in nonlinear regime. CW: Continuous-wave laser. LO: Local oscillator. PD: Photodetector. LNA: Low-noise amplifier. BPF: Band-pass filter. HPA: High-power amplifier. DCA: Digital communications analyzer.
Measurements in the setup in Fig. 10; (a) optical data monocycles; (b) RF spectrum of UWB monocycles at 57 GHz; (c) eye diagram of down-converted data monocycles.
In the techniques in Fig. 7 and Fig. 10, biasing the MZM employed for up-conversion at minimum transmission point requires half of the LO frequency and reduces the RF power fading effect due to fibre chromatic dispersion (Ma et al., 2007), however higher power is required in the system to not degrade performance with respect to bias at quadrature point. In addition, in both techniques baseband signal is also available after photodetection, which could be provided via a wired connection and a user could employ a simple, low-cost receiver to detect the signal by filtering out the millimetre-wave signal. Also, the baseband signal could meet the UWB mask in the 3.1-10.6 GHz band and be radiated employing an antenna with a suitable frequency response (Pan & Yao, 2009a).
\n\t\t\t\tAs described in the previous section, optical generation of impulse-radio signals can be achieved employing pulsed laser sources. The overall RoF performance depends directly on the characteristics of the specific pulsed laser employed. In particular, polarization stability i.e. the variation of polarization over time is of special importance when external modulation is employed.
\n\t\t\t\t\tThe polarization stability of a pulsed laser source can cause spectrum distortion. The experimental setup for the characterization of the polarization stability of a femtosecond pulsed laser is depicted in Fig. 12. A computer controls the process of capture and storage of data.
\n\t\t\t\t\tExperimental setup to characterize the polarization stability of pulsed lasers. PC: Polarization controller. OSA: Optical spectrum analyzer.
The polarization stability and the distortion of the laser spectrum are evaluated for linear horizontal polarization (LH) with an orientation of 0º (launched polarization) adjusted by the polarization controller in Fig. 12. In practice, the orientation adjusted is ~3.6º (LH+3.6º). The optical spectrum analyzer captures the spectrum with 0.05 nm resolution bandwidth and -80 dBm sensitivity. The evaluation is performed at different wavelengths at which the spectrum gets distorted for different launched polarizations. The measurement time is 24 h.
\n\t\t\t\t\t\n\t\t\t\t\t\tFig. 13 (a) shows the orientation Ψ (LH+Ψ) calculated from the normalized Stokes vector (S1, S2, S3) given by the polarization analyzer as a function of time. Abrupt changes in the behaviour are due to abrupt temperature changes (disconnection/connection of conditioned air) in the laboratory measurement environment. Fig. 13 (b) is a plot of Poincare sphere showing the evolution over time of the normalized Stokes vector. From the Stokes vector other parameters characterizing polarization such as the degree of polarization (DOP), degree of linear polarization (DOLP), degree of circular polarization (DOCP) and ellipticity can also be calculated.
\n\t\t\t\t\tCharacterization of the polarization stability of a femtosecond pulsed laser; (a) Orientation; (b) Poincare sphere; (c) spectra over 1 h.
\n\t\t\t\t\t\tFig. 13 (c) shows the evolution of spectrum over time for a measurement time of 1 h over a zone in which the temperature is stable. The polarization stability, expressed as the standard deviation of the normalized Stokes parameters, is lower than 0.001 at 1 h independently on the wavelength at which is evaluated.
\n\t\t\t\tIn RoF systems, analog radio signals are modulated on the intensity of the optical signals (E/O conversion) to be transmitted over an optical fibre link employing either directly modulated lasers or external modulators, as shown in Fig. 1. Directly modulated semiconductor lasers such as DFB lasers and VCSELs are preferred due to lower cost whilst for high frequencies the required performance can be satisfied only by externally modulated transmitters.
\n\t\t\t\tIt has been shown that a VCSEL has higher RF to optical power conversion efficiency than an external MZM and a DFB laser diode for the same output optical power (Gamage et al., 2008a; Gamage et al., 2008b). In addition, in case of the bandwidth is not a limiting factor direct modulation of a DFB laser leads to less distortion on UWB signals than external modulation with MZM because of its less nonlinearity, for the same output power (Jazayerifar et al., 2008). In addition, impulse-radio UWB signals are more sensitive to nonlinear distortion and less sensitive to noise than OFDM UWB signals for the same transmitted energy due to the higher peak-to-peak power. In practice, higher modulated power can be obtained with MZM but increasing the input optical power. The impact of laser chirp on UWB signals is almost negligible, but it affects the amount of dispersion when the UWB signal is transmitted over fibre.
\n\t\t\t\tMost of the UWB RoF systems have focused on SMF which is best suited for long-distance access applications. RoF in combination with MMF fibres can be deployed within homes and office buildings for baseband digital data transmission supporting 3.5 GHz wireless signals. The large core diameter of MMF fibres (typically 50 μm or 62.5 μm) offers easier installation and maintenance in within-building environments and reduced cost compared to SMF (Koonen & Garcia, 2008). Note that MMF is also widely used in within-building fibre installations for baseband data transmission systems at far more than 10 Gbit/s. Compared to silica MMF, graded-index plastic optical fibres (GI-POF) offer further advantages such as smaller bending radius, better tolerance to tensile load and stress, and simpler connectorization.
\n\t\t\t\tA RoF system employing VCSEL direct modulation of impulse-radio UWB signals in the 3.1-10.6 GHz band has been demonstrated over 100 m MMF (Jensen et al., 2009). Error-free operation employing FEC is achieved at a wireless distance of 8 m at 2.5 Gbit/s or 4 m at 4 Gbit/s. Impulse-radio UWB generation employing DFB direct modulation and transmission over 100 m GI-POF has also been recently demonstrated (Abraha et al., 2009).
\n\t\t\t\tIn this section, an analysis of impulse-radio UWB propagation on standard SMF is presented. The analysis compares two modulation schemes: External modulation in a MZM at 1550 nm and direct modulation in a VCSEL at 1310 nm. Fig. 14 shows the two UWB radio-over-fibre implementations considered. The analysis targets to evaluate the impact of the modulation index on the reach and has been performed employing the commercial simulation tool VPITransmissionMakerTM (version 7.5).
\n\t\t\t\tImpulse-radio UWB RoF optical link configuration and VCSEL characteristics. CW: Continuous-wave laser. PD: Photodetector. Amp: Amplifier. Att: Variable attenuator. LPF: Low-pass filter. BERT: BER test.
\n\t\t\t\t\tTable 1 summarises the parameters of the components shown in Fig. 14 employed in the analysis. Typical parameters of commercially available components are considered.
\n\t\t\t\tCW param value | \n\t\t\t\t\t\t\tMZM param v alue | \n\t\t\t\t\t\t\tPhotodiode PIN par am value | \n\t\t\t\t\t\t
Laser power 10 dBm | \n\t\t\t\t\t\t\tChirp 0 | \n\t\t\t\t\t\t\tResponsivity 0.65 A/W | \n\t\t\t\t\t\t
RIN -13 0 dB/Hz | \n\t\t\t\t\t\t\t5 V | \n\t\t\t\t\t\t\tDark current 5 nA | \n\t\t\t\t\t\t
Amplifier param value | \n\t\t\t\t\t\t\tVπ RF 5V | \n\t\t\t\t\t\t\tThermal noise 10pA/Hz | \n\t\t\t\t\t\t
Gain 40 dB | \n\t\t\t\t\t\t\tInsertion losses 6 dB | \n\t\t\t\t\t\t\tVCSEL param value | \n\t\t\t\t\t\t
Noise factor 3.8 dB | \n\t\t\t\t\t\t\tExtinction ratio 35 dB | \n\t\t\t\t\t\t\tCore radius 2·10 -6 m | \n\t\t\t\t\t\t
L O param value | \n\t\t\t\t\t\t\tLPF param value | \n\t\t\t\t\t\t\tActive region Thickness 0.3·10 -6 m | \n\t\t\t\t\t\t
Power 7 dBm Frequency 3.75 GHz | \n\t\t\t\t\t\t\tLPF type Bessel 4th order | \n\t\t\t\t\t\t\tConfinement factor 0.03 | \n\t\t\t\t\t\t
Bandwidth 3 GHz | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t |
UWB radio-over-fibre parameters employed in the setup in Fig. 14.
The impulse-radio UWB signal consists of fifth-derivative Gaussian pulses at 5.4 GHz 10-dB bandwidth, which are compliant with current UWB regulation in the 3.1-10.6 GHz band. This signal is OOK-modulated with 214-1 pseudo-random bit sequence (PRBS) data at 1.25 Gbit/s resulting the data UWB pulses to be modulated. Both MZM and VCSEL are biased in linear regime, MZM at its quadrature bias point and VCSEL at the centre of the linear zone of its L-I curve, i.e. at (I\n\t\t\t\t\t\n\t\t\t\t\t\tth\n\t\t\t\t\t\n\t\t\t\t\t+I\n\t\t\t\t\t\n\t\t\t\t\t\tsat\n\t\t\t\t\t)/2 where I\n\t\t\t\t\t\n\t\t\t\t\t\tth\n\t\t\t\t\t is the threshold current of 1 mA and I\n\t\t\t\t\t\n\t\t\t\t\t\tsat\n\t\t\t\t\t is the saturation current of 3.5 mA which corresponds to the 1-dB compression point. Fig. 14 shows the V-I and L-I curves of the commercial VCSEL at 27 ºC in the analysis. At each modulation index, the attenuator sets a maximum PSD of -41.3 dBm/MHz at the radiation point (1) in Fig. 14. This power level would meet the UWB mask in current regulation employing a transmitter antenna with 0 dBi gain. Down-conversion to baseband is performed by electrical mixing (6.5 dB conversion losses) to obtain a suitable eye diagram for BER performance evaluation. Optical noise is predominant at receiver so that a Chi2 method is employed for BER estimation. BER performance at different fibre lengths is compared with the back-to-back (B2B) configuration (with no fibre transmission) to evaluate the fibre degradation. Fig. 15 shows the BER results. External modulation gives a maximum reach of 50 km at error-free operation (BER< 10-9) at 0.25 modulation index. Direct modulation gives a maximum reach of 25 km at 0.16 modulation index. Higher modulation indexes than these shown in Fig. 15 result in distortion which makes the UWB spectrum non-compliant with regulation. Longer reach could be achieved employing a pre-amplifier at receiver or forward error correction codes (FEC) (BER< 2.2∙10-3) at expense of increased complexity. Fig. 16 and Fig. 17 show examples of UWB signal and down-converted signal for external and direct modulation, respectively.
\n\t\t\t\tPerformance of impulse-radio UWB over SMF as a function of the modulation index; (a) External modulation in a MZM; (b) Direct modulation in a VCSEL.
Impulse-radio UWB signal at point (1) in Fig. 14 (a) RF spectrum and (b) time-domain, (c) down-converted eye diagram at 0.2 external modulation index for B2B configuration. (d-f) the same for 40 km SMF.
Impulse-radio UWB signal at point (1) in Fig. 14 (a) RF spectrum and (b) time-domain, (c) down-converted eye diagram at 0.16 direct modulation index for B2B configuration. (d-f) the same for 20 km SMF.
In this chapter, the principles and state-of-the-art of RoF technology has been presented. The use of optical sources for the generation of impulse-radio UWB RoF, as one of the most challenging applications to date, has been described and the expected performance after optical transmission has been presented. A technique based on frequency up-conversion of optical UWB signals in a MZM in nonlinear regime has been presented. This technique permits the optical generation of UWB monocycles at 57 GHz bearing data at 1.244 Gbit/s. The generation and further transmission of impulse-radio UWB over 100 m of SMF has been demonstrated with good quality pulses. Another technique performing up-conversion in a MZM of optical pulses with subsequent electrical UWB shaping has been demonstrated at 16.85 GHz bearing data at 1.244 Gbit/s with good quality. The polarization stability of a pulsed laser has also been presented as key factor limiting system performance. Finally, the RoF distribution of impulse-radio UWB has been analyzed over long-distance SMF links suitable for access networks. The longest transmission reach is achieved employing external modulation in a MZM.
\n\t\tEconomic losses due to bovine mastitis is estimated to be $2 billion in the United States alone [1]. Most studies showed that there is no widespread, emerging resistance among mastitis pathogens [2, 3, 4] in dairy farms. Some studies showed that the antimicrobial resistance of mastitis pathogens varies with dairy farms and bacterial species within and among dairy farms [4, 5, 6, 7, 8, 9]. However, antimicrobial resistance patterns of human pathogenic bacteria and their resistome in dairy farms might be of significant concern.
\nOn average, starting from calving (giving birth) dairy cow is milked (in lactation) for about 300 days and then dried off (stop milking) for about 60 days before they calve again. Under the ideal dairy farming condition, a dairy cow should become pregnant within 60 days of calving, and the lactation cycle continues (Figure 1). The goal of a dry period is to give them a break from milking so that milk-producing cells regenerate, multiply, and ready for the next cycle of lactation. The incidence of intramammary infection (IMI) by bacteria is high during the early dry period and transition periods [10]. In general, for a dairy cow, a transition period, also known as the periparturient period, is a time range from three weeks before parturition (non-milking time) until three weeks after calving (milking time). It is a transition time from non-milking to milking.
\nAntimicrobials usage patterns during the lactation cycle. DIM: Days in milk, yellow star: Peak lactation at 60 DIM, green bars: Energy demand that requires the mobilization of body energy reserve at the expense of losing bodyweight, red bumps showed increased usage of antimicrobials.
Dairy cows are susceptible to mastitis during early non-lactating (dry period) and transition periods [11, 12], especially new infection with environmental pathogens (Streptococcus spp. and coliform) are highest during the first two weeks after drying off and last two weeks before calving [13] compared to contagious mastitis pathogens such as S. aureus [14]. The incidence of intramammary infection is high during the early dry period because of an absence of hygienic milking practices such as pre-milking teat washing and drying [15], pre- and post-milking teat dipping in antiseptic solutions [16, 17], that are known to reduce teat end colonization by bacteria and infection. An udder infected during the early dry period usually manifests clinical mastitis during the transition period [18] because of increased production of parturition inducing immunosuppressive hormones [19], negative energy balance [12], and physical stress during calving [20].
\nCows are naturally protected against intramammary infections during the dry period by physical barriers such as the closure of teat opening by smooth muscle (teat sphincter) and the formation of a keratin plug, fibrous structural proteins (scleroproteins) [21, 22], in the teat canal produced by teat canal epithelium [23]. Keratin contains a high concentration of fatty acids, such as lauric, myristic, and palmitoleic acids, which are associated with reduced susceptibility to infection and stearic, linoleic, and oleic acids that are associated with increased susceptibility to infection. Keratin also contains antibacterial proteins that can damage the cell wall of some bacteria by disrupting the osmoregulatory mechanism [23]. However, the time of teat canal closure varies among cows. Some studies showed that 50% of teat canals were classified as closed by seven days after drying off, 45% closed over the following 50–60 days after drying off, and 5% had not closed by 90 days after dry off [24]. Teats that do not form a plug-like keratin seal are believed to be most susceptible to infection. Infusion of long-acting antimicrobials into the udder at drying-off (dry cow therapy) has been the major management tool for the prevention of IMI during the dry period, as well as to clear IMI established during the previous lactation [24].
\nIn the United States and many other countries at the end of lactation (at drying off), all cows regardless of their health status, are given an intramammary infusion of long-acting antimicrobials (blanket dry cow therapy) to prevent IMI by bacteria during the dry period [3, 25]. Because of increased concern on the use of blanket dry cow therapy for its role in driving antimicrobial resistance, selective dry cow therapy (intramammary infusion of antimicrobials into only quarters that have tendency or risk of infection) has been under investigation [26, 27]. Some recent studies showed that the use of bacteriological culture-based selective dry cow therapy at drying-off did not negatively affect cow health and performance during early lactation [26, 27]. In general, dairy farms are one of the largest users of antimicrobials including medically important antimicrobials [28]. Some of the antimicrobials used in dairy farms include beta-lactams (penicillins, Ampicillin, oxacillin, penicillin-novobiocin), extended-spectrum beta-lactams (third-generation cephalosporins, e.g., ceftiofur), aminoglycosides (streptomycin), macrolides (erythromycin), lincosamide (pirlimycin), tetracycline, sulfonamides, and fluoroquinolones [28, 29, 30]. Antimicrobials are also heavily used in dairy farms for the treatment of cases of mastitis [3, 25, 31] and other diseases of dairy cows such as metritis, retained placenta, lameness, diarrhea, pneumonia, [32, 33, 34, 35, 36] and neonatal calf diarrhea [37]. Over 90% of dairy farms in the US infuse all udder quarters of all cows with antimicrobial regardless of their health status [7, 25, 38]. According to dairy study in 2007 that was conducted in 17 major dairy states in the United States, 85.4% of farms use antibiotics for mastitis, 58.6% for lameness, 55.8% for diseases of the respiratory system, 52.9% for diseases of reproductive system, 25% for diarrhea or gastrointestinal infections and 6.9% for all other health problems [3, 25]. Cephalosporins were the most widely used antibiotics for the treatment of mastitis, followed by lincosamides and non-cephalosporin beta-lactam antibiotics [3, 25]. The two most commonly used antibiotics for dry cow therapy are Penicillin G/dihydrostreptomycin and cephalosporins [3, 25]. Antimicrobials were administered for the prevention and treatment of mastitis and other diseases of dairy cattle mainly through intramammary infusion and intramuscular route (USDA APHIS, 2009a). Antimicrobials infused into the mammary glands can be excreted to the environment through leakage of milk from the antimicrobial-treated udder or absorbed into the body and enter the blood circulation and biotransformed in the liver or kidney and excreted from the body through urine or feces into the environments [39, 40, 41, 42]. Similarly, antimicrobials administered through parenteral routes for the treatment of acute or peracute mastitis or other diseases of dairy cows will enter the blood circulation and biotransformed in the liver or kidney and excreted from the body through urine or feces into the environments [39, 40, 41, 42]. Therefore, both parenteral and intramammary administration of antibiotics has a significant impact on other commensals or opportunistic bacteria in the gastrointestinal tract of dairy cows and farm environments.
\nIn addition to the use of antimicrobials for the prevention and treatment of mastitis and other diseases of dairy cattle, some farms also feed raw waste milk or pasteurized waste milk from antibiotic-treated cows to dairy calves. Feeding of raw waste milk or pasteurized waste milk from antibiotic-treated cows to calves increases pressure on gut microbes such as E. coli to became antimicrobial-resistant [43, 44, 45]. Aust et al. [43] showed that the proportion of antimicrobial-resistant E. coli, especially cephalosporin-resistant E. coli isolates, was significantly higher in calves fed waste milk or pasteurized waste milk from antimicrobial treated cows than calves fed bulk tank milk from non-antibiotic treated cows. However, pasteurized waste milk from cows not treated with antimicrobials is acceptable to be feed to young calves [43] but it is not known if pasteurization prevents the transfer of antimicrobial-resistant genes to microbes in the calve’s gut. Some studies also showed that feeding pasteurized waste milk from antimicrobial treated cows to calves increased the presence of phenotypic resistance to ampicillin, cephalothin, ceftiofur, and florfenicol in fecal E. coli compared with milk replacer-fed calves [45]. However, the presence of resistance to sulfonamides, tetracyclines, and aminoglycosides was common in dairy calves regardless of the source of milk, suggesting other driving factors for resistance development [45]. It has been suggested that antimicrobial residues present in waste milk have a non-specific effect at a lower taxonomical level [44]. Collectively, these non-prudent antimicrobials usage practices in dairy farms expose a large number of animals in dairy farms to antimicrobials and also increases the use of antimicrobials in dairy farms, which in turn creates intense pressure on microbes in animals’ body especially commensal and opportunistic microbes in the gastrointestinal tract and farm environments. Some of these commensal bacteria in the animal body are serious human pathogens (e.g., E. coli 0157:H7). Staphylococcus aureus is one of the pathogens with a known ability to develop antimicrobial resistance and established S. aureus infections are persistent and difficult to clear. The failure to control these infections leads to the presence of reservoirs in the dairy herd, which ultimately leads to the spread of the infection and the culling of the chronically infected cows [46, 47].
\nMonitoring antimicrobial resistance patterns of bacterial isolates from cases of mastitis is important for treatment decisions and proper design of mitigation measures. It also helps to determine emergence, persistence, and potential risk of the spread of antimicrobial-resistant bacteria and resistome to human, animal, and environment [48, 49]. The prudent use of antimicrobials in dairy farms reduce emergence, persistence, and spread of antimicrobial-resistant bacteria and resistome from dairy farms to human, animal, and environment.
\nMost studies showed that there is no widespread, emerging resistance among mastitis pathogens [2, 3, 4] in dairy farms. However, dairy farms may serve as a source of antimicrobial-resistant human pathogenic bacteria. Extensive use of third-generation cephalosporins (3GCs) in dairy cattle for the prevention and treatment of mastitis [3, 25, 28] and other diseases of dairy cattle [31, 32] can result in the carriage of extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL Ent) [50, 51]. Third- and fourth-generation cephalosporins are commonly used for the treatment of invasive Gram-negative bacterial infections in humans [52, 53, 54]. In 2017, there were an estimated 197,400 cases of ESBL Ent among hospitalized patients and 9100 estimated deaths in the US alone [55]. Among Enterobacteriaceae, Escherichia coli (E. coli) is the most common bacteria that reside in the gut as normal microflora or opportunist pathogen of animals and humans. However, certain pathogenic strains can cause diseases such as mastitis in cattle, neonatal calf diarrhea in calves and hemorrhagic enteritis, and more life-threatening conditions such as hemolytic uremic syndrome and urinary tract infections in humans. New strains of multi-drug resistant foodborne pathogens that produce extended-spectrum beta-lactamases that inactivate nearly all beta-lactam antibiotics have been reported [30]. Ceftiofur is the most common 3GC used in dairy cattle operations [56]. The 3GCs are also critically important antibiotics for the treatment of serious infections caused by Enterobacteriaceae such as Escherichia coli (E. coli) and Salmonella spp. in humans [57, 58]. The use of structurally and chemically similar antibiotics in dairy cattle production and human medicine may lead to co-resistance or cross-resistance [52, 53, 54]. Some of the species of Gram-negative environmental mastitis pathogens, such as E. coli, Klebsiella pneumoniae, Acinetobacter spp., Pseudomonas spp., Enterobacter spp. are the greatest threat to human health due to the emergence of strains that are resistant to all or most available antimicrobials [59, 60].
\nThe resistance of Enterobacteriaceae to 3GC is mainly mediated by the production of extended-spectrum beta-lactamase enzymes (ESBLs) that breakdown 3GC [61]. E. coli is one of the most frequently isolated Enterobacteriaceae carrying ESBL genes (blaCTX-M, blaSHV, blaTEM, and blaOXA\n) families [62, 63, 64]. These ESBL genes are usually carried on mobile plasmids along with other resistance genes such as tetracycline, quinolones, and aminoglycosides. E. coli resides in the gastrointestinal tract of cattle as normal or opportunistic microflora, but some strains (for e.g., 0157:H7) cause serious infection in humans [58], indicating that cattle could serve as a reservoir of ESBLs producing E. coli (ESBLs E. coli) for human.
\nIn the US, the occurrence of ESBLs E. coli in the dairy cattle was reported a decade ago from Ohio [52] and few previous studies reported the occurrence and an increase in the trend of ESBLs E. coli in the dairy cattle production system [52, 53, 65, 66, 67]. However, recent studies increasingly showed the rise of ESBLs E. coli in the cattle [51, 52, 65, 67]. Similarly, reports from the Center for Disease Control (CDC) showed a continuous increase in the number of community-associated human infections caused by ESBLs-producing Enterobacteriaceae [55]. This CDC report showed a 9% average annual increase in the number of hospitalized patients from ESBLs pathogens in six consecutive years (from 2012 to 2017). As a result, the human health sector tends to blame dairy farms that routinely use the 3GC for the rise of ESBLs pathogens such as E. coli [55, 68]. However, despite the general believe of possibility of transmission of antimicrobial-resistant bacteria from dairy farms to humans directly through contact or indirectly through food chain, there was no clear evidence-based data that showed the spread of antimicrobial-resistant bacteria from the dairy production system to humans. The opinion of the scientific community on the factors that drive the emergence and spread of antimicrobial-resistant bacteria also varies [69]. Transmission of an antimicrobial-resistant pathogen to humans could occur if contaminated unpasteurized milk and/or undercooked meat from culled dairy cows due to chronic mastitis is consumed [70]. So it is crucial to pasteurize milk or cook meat properly to reduce the risk of infection by antimicrobial-resistant bacteria [71]. It is not known, if pasteurization or proper cooking prevents the transfer of resistant genes from milk or meat to commensal or opportunistic bacteria in the human gastrointestinal tract (GIT), or the GIT of calves fed pasteurized waste milk. Mechanisms of antibiotic resistance gene transfer from resistant to susceptible bacteria are not well known, and killing resistant pathogens alone may not be good enough to prevent the transfer of the resistance gene. Non-prudent use of antimicrobials in dairy farms increases selection pressure, which could result in the emergence, persistence, and horizontal transfer of antimicrobial-resistant determinants from resistant to non-resistant bacteria. Bacteria exchange resistance genes through mobile genetic elements such as plasmids, bacteriophages, pathogenicity islands, and these genes may ultimately enter bacteria pathogenic to humans or commensal or opportunistic bacterial pathogens. The prudent use of antimicrobials in dairy farms requires identification of the pathogen causing mastitis, determining the susceptibility/resistance of the pathogen, and proper dose, duration, and frequency of treatment to ensure effective concentrations of the antibiotic to eliminate the pathogen.
\nDespite decades of research to develop effective vaccines against major bacterial bovine mastitis pathogens such as Staphylococcus aureus, Streptococcus uberis, and E. coli, the effective intramammary immune mechanism is still poorly understood, perpetuating reliance on antibiotic therapies to control mastitis in dairy cows. Dependence on antimicrobials is not sustainable because of their limited efficacy [46, 47] and increased risk of emergence of antimicrobial-resistant bacteria that pose serious public health threats [4, 72, 73, 74]. Neither of the two currently available commercial Bacterin vaccines against S. aureus (Table 1), Lysigin® (Boehringer Ingelheim Vetmedica, Inc., St. Joseph, MO) in the USA and Startvac® (Hipra, Girona, Spain) in Europe and other countries, confer protection from new intramammary infection under field trials as well as under controlled experimental challenge studies [75, 76, 77, 78, 79, 80, 81].
\n\nMastitis Pathogen\n | \nVaccine | \nVaccine component | \nProtective effect | \nReference | \n
---|---|---|---|---|
\n | Commercial | \n\n | \n | \n |
\nS. aureus\n | \nLysigin® | \nBacterin: Somatic antigen containing phage types I, II, III, IV with different strains of S. aureus\n | \nReduced SCC, clinical mastitis, and chronic IMI | \n[85, 86, 87] | \n
“ | \n“ | \nField-based studies concluded no such effect | \n[80, 81, 88, 89, 90] | \n|
\n | Startvac® | \nBacterin: E. coli J5 and S. aureus CP type 8 with SAAC | \nDecreased duration of IMI, transmissibility of S. aureus, coliforms, and CNS | \n[77] | \n
“ | \n“ | \nUse of the vaccine was not associated with a decrease in mastitis | \n[75] | \n|
\n | Bestvac® Vs Startvac | \nherd-specific autologous vaccine compared with Startvac® | \nBoth vaccines decreased herd prevalence of S. aureus mastitis but no other differences in terms of improvement of udder health | \n[78] | \n
\n | Experimental | \n\n | \n | \n |
\n | Whole-cell lysate | \nBacterin encapsulated in biodegradable microspheres | \nInduced antibodies that were more opsonic for neutrophils and inhibited adhesion to mammary epithelium. | \n[91] | \n
\n | Whole-cell lysate from two strains | \nBacterin from two strains (α and α + β hemolytic) plus supernatants from non-hemolytic strain | \nVaccinated cows had 70% protection from infection compared to less than 10% protection in control cows | \n[92] | \n
\n | MASTIVAC I | \nWhole-cell lysate | \nImproved udder health in addition to specific protection against S. aureus infection | \n[93] | \n
\n | Live pathogenic S. aureus through IM route | \nLive pathogenic S. aureus\n | \nInduce activation of immune cells in mammary gland and blood | \n[94] | \n
\n | Fibronectin binding protein and clumping factor A | \nDNA primed and protein boosted | \nInduced cellular and humoral immune responses that provide partial protection against S. aureus\n | \n[95] | \n
\n | Protein A of S. aureus with the green fluorescent protein | \nDNA | \nInduced humoral and cellular immune responses | \n[96] | \n
\n | Plasmid encoding bacterial antigen β-gal | \nDNA | \nInduced humoral and cellular immune responses | \n[97] | \n
\n | Polyvalent S. aureus Bacterin | \nBacterin | \nEliminated some cases of chronic intramammary S. aureus infections | \n[88] | \n
\n | Lysigin® with three-isolates based experimental Bacterin | \nBacterin | \nLysigin reduced the clinical severity and duration of clinical disease. None of the experimental Bacterins has significant effects | \n[80] | \n
\n | Polyvalent S. aureus Bacterin | \nBacterin + antibiotic therapy | \n\nS. aureus intramammary infection cure rate increased | \n[89] | \n
\n | Whole-cell lysate | \nWhole-cell trivalent vaccine containing CP types 5, 8 and 336 with FIA or Alum adjuvants | \nElicited antibody responses specific to the 3 capsular polysaccharides | \n[98] | \n
\n | CP conjugated to a protein and incorporated in polymicrospheres and emulsified in FIA | \nCP types 5, 8 and 336 | \nCows in both groups produced increased concentrations of IgG1, IgG2 antibodies, hyperimmune sera from immunized cows increased phagocytosis, decreased bacterial adherence to epithelial cells | \n[99] | \n
\n | Polysaccharide-protein conjugates in FIA | \nPolysaccharide-protein conjugate | \n||
\n | SASP or SCSP | \nSurface proteins | \nInduced partial protection | \n[100] | \n
\n | Vaccination with Efb and LukM | \n\n | Induced increased titers in serum and milk | \n[101] | \n
\n | Inactivated Bacterin | \nBacterin | \nPartial protection | \n[102] | \n
\nS. uberis\n | \nCommercial | \n\n | \n | \n |
\n | UBAC® | \nExtract from biofilm-forming strains of S. uberis\n | \nReduce clinical signs, bacterial count, temperature, daily milk yield losses and increased the number of quarters with isolation and somatic cell count <200,000 cells/mL of milk | \n[84] | \n
\n | Experimental | \n\n | \n | \n |
\n | Killed S. uberis cells\n | \nBacterin | \nReduced numbers of homologous S. uberis in milk | \n[103] | \n
\n | Killed bacterial cells | \nBacterin of S. uberis and S. agalactiae\n | \nParenteral vaccination has no effect on streptococcal mastitis | \n[104, 105] | \n
\n | Live S. uberis/ cutaneous route | \nLive S. uberis\n | \nSome protective effect only on the homologous strain | \n[106] | \n
\n | GapC or chimeric CAMP factor | \nProtein | \nReduction in inflammation | \n[107] | \n
\n | PauA | \nprotein | \nPartial protection | \n[108] | \n
Coliform | \nCommercial | \n\n | \n | \n |
\n | \nE. coli J5 Mastiguard® J Vac® Endovac-bovi® (IMMVAC) | \nBacterin | \nReduce bacterial counts in milk, duration of IMI and resulted in fewer clinical symptoms | \n[82, 83, 109, 110, 111] | \n
Commercialized and experimental vaccines against major bovine mastitis pathogens.
SAAC: slime associated antigenic complex, SASP: Staphylococcus aureus surface proteins, SCSP: Staphylococcus chromogenes surface proteins, CP: Capsular polysaccharide, GapC: Glyceraldehyde-3-phosphate dehydrogenase C, pauA: plasminogen activator protein, FIA: Freund’s incomplete adjuvant, Efb: fibrinogen-binding protein, LukM: leukocidin subunit M.
There are four commercial vaccines against E. coli mastitis which include 1) the Eviracor®J5 (Zoetis, Kalamazoo, MI), [82, 83], 2) Mastiguard®, 3) J-VAC® (Merial-Boehringer Ingelheim vet medical, Inc., Duluth, GA) and 4) ENDOVAC-Bovi® (IMMVAC) (Endovac Animal Health, Columbia, MO) (Table 1). The Endovac-bovi® is a cross-protective vaccine made of genetically engineered R/17 mutant strain of Salmonella typhimurium and the core somatic antigen mutant J-5 strain of E. coli combined with an immune-potentiating adjuvant (IMMUNEPlus®). Endovac-bovi significantly reduces diseases caused by Gram-negative bacteria producing various endotoxins and protects against E. coli mastitis and other endotoxin-mediated diseases caused by E. coli, Salmonella, Pasteurella multocida, and Mannheimia hemolytica. The UBAC® (Hipra, Amir, Spain) [84] is a recently developed vaccine against S. uberis mastitis with label claim of partial reduction in clinical severity of S. uberis mastitis.
\nIntramammary immunity can be induced locally in the mammary gland or systemically in the body and cross from the body into the mammary glands. Mammary gland pathogen that enters through teat opening interact with host innate defense system primarily with macrophages in the mammary gland. Macrophages recognize invading pathogens through its pattern recognition receptors (PRR) which binds to pathogen associated molecular patterns (PAMPs) and engulf and break down the foreign pathogen into small peptides and load on to MHC-II molecules move to the supramammary lymph nodes and display on its surface to the T cells. Naïve T cells bind with peptide on MHC-II molecule through its T- cell receptor and become activated and start secreting cytokines, which further stimulate B-cells to produce antibodies. Antibody produced by B-cells released into the blood circulation and depending on type of antibody may be released to the site of infection (e.g., IgG) and opsonize the infecting pathogen and subject them to destruction by opsonophagocytic mechanisms. Antibodies may also remain on mucosal surfaces (e.g., IgA) and bind to invading pathogens and prevent them from binding to host cells or tissue and thereby prevent colonization and infection.
\nIntramammary infection (IMI) leads to increased somatic cell count in the milk or mammary secretion. Somatic cells are mainly white blood cells such as granulocytes (neutrophils, eosinophils, and basophils), monocytes or macrophages, and lymphocytes, which are recruited to the mammary glands in response to mammary gland infection to fight off infection. A small proportion of mammary epithelial cells that produce milk are also shed through milk and are included in the somatic cell count. So, somatic cells are white blood cells and mammary epithelial cells. Milk somatic cell count (SCC) increases when there is mammary gland infection (IMI) because of an inflammatory response to clear infection. In general, SCC is also an indicator of milk quality [112, 113, 114, 115, 116] because if there are few mammary pathogenic bacteria in the gland, the inflammatory response is less, and somatic cells recruitment into the gland is also low and vice versa. Bulk tank milk (BTM) is milk collected from all lactating dairy cows in a farm into a tank or multiple tanks. So BTSCC is somatic cell counts obtained from milk sample collected from a tank.
\nIntramammary infection may progress to clinical or subclinical mastitis [117]. Clinically infected udder usually treated with antimicrobial, whereas subclinically infected udder may not be diagnosed immediately and treated but remained infected and shedding bacteria through milk throughout lactation. The proportion of cure following treatment of mastitis varies and the variation in cure rate is multi-factorial including cow factors (age or parity number, stage of lactation, and duration of infection, etc.), management factors (detection and diagnosis of infection and time from detection to treatment, availability of balanced nutrition, sanitation, etc.), factors related to antimicrobial use patterns (type, dose, route, frequency, and duration), and pathogen factors (type, species, number, pathogenicity or virulence, resistance to antimicrobial, etc.) [46, 118].
\nThe dilution of effector humoral immune responses by large volume of milk coupled with the ability of mastitis causing bacteria to develop resistance to antimicrobials makes the control of mastitis very difficult. Therefore, the development of an alternative preventive tool such as a vaccine, which can overcome these limitations, has been a crucial focus of current research to decrease not only the incidence of mastitis but also the use of antimicrobials in dairy cattle farms. Most vaccination strategies against mastitis have focused on the enhancement of humoral immunity. Development of vaccines that induce an effective cellular immune response in the mammary gland has not been well investigated. The ability to induce cellular immunity, especially neutrophil activation and recruitment into the mammary gland, is one of the key strategies in the control of mastitis, but the magnitude and duration of increased cellular recruitment into the mammary gland leads to a high number of somatic cells and poor-quality milk. So, effective balanced humoral and cellular immunity that clear intramammary infection in a short period of time is required. Several vaccine studies were conducted over the years under controlled experimental and field trials. The major bacterial bovine mastitis pathogens that have been targeted for vaccine development are S. aureus, S. uberis, and E. coli [119]. Most of these experimental and some commercial vaccines are Bacterins which are inactivated whole organism, and some vaccines contained subunits of the organism such as surface proteins [100], toxins, or polysaccharides.
\n\nStaphylococcus aureus is one of the most common contagious mastitis pathogens, with an estimated incidence rate ranging from 43–74% [25, 38, 56, 120, 121]. Staphylococcus chromogenes is another increasingly reported coagulase-negative Staphylococcus species with an estimated quarter incidence rate of 42.7% characterized by high somatic cell counts [122, 123, 124, 125, 126, 127, 128]. In a study on conventional and organic Canadian dairy farms, coagulase-negative Staphylococcus species were found in 20% of the clinical samples [129]. Recently, mastitis caused by coagulase-negative Staphylococcus species increasingly became more problematic in dairy herds [125, 127, 130, 131].
\nSeveral staphylococcal vaccine efficacy trials showed that vaccination with Bacterin vaccines induced increased antibody titers in the serum and milk that are associated with partial protection [75, 76, 77, 80, 132, 133, 134] or no protection at all [78, 79, 81]. However, effective intramammary immune mechanisms against staphylococcal mastitis is still poorly understood. None of the commercially available Bacterin vaccines protects new intramammary infection [75, 77, 80, 81]. Dependence on antibiotics for the prevention and treatment of mastitis is not sustainable because of limited success [46, 47] and the emergence of antimicrobial-resistant bacteria that are major threat to human and animal health [72, 73, 74].
\nDespite several mastitis vaccine trials conducted against S. aureus mastitis [75, 77, 80, 88, 89, 91, 93, 94, 95, 97, 98, 99, 133] all field trials have either been unsuccessful or had limited success. There are two commercial vaccines for Staphylococcus aureus mastitis on the market, Lysigin® (Boehringer Ingelheim Vetmedica, Inc., St. Joseph, MO) in the United States and Startvac® (Hipra S.A, Girona, Spain) in Europe and Canada [78]. None of these vaccines confer protection under field trials as well as under controlled experimental studies [75, 77, 80, 81]. Several field trials and controlled experimental studies have been conducted testing the efficacy of Lysigin® and Startvac®, and results from those studies have shown some interesting results, namely a reduced incidence, severity, and duration of mastitis in vaccinated cows compared to non-vaccinated control cows [75, 76, 77]. Contrary to these observations, other studies failed to find an effect on improving udder health or showed no difference between vaccinated and non-vaccinated control cows [78, 79]. None of these Bacterin-based vaccines prevents new S. aureus IMI [75, 77, 80, 81]. Differences found in these studies are mainly due to methodological differences (vaccination schedule, route of vaccination, challenge model, herd size, time of lactation, etc.) in testing the efficacy of these vaccines. It is critically important to have a good infection model that mimics natural infection and a model that has 100% efficacy in causing infection. Without a good challenge model, the results from vaccine efficacy will be inaccurate.
\nThe Startvac® (Hipra, Girona, Spain) is the commercially available vaccine in Europe and is a polyvalent vaccine that contains E. coli J5 and S. aureus strain SP140 [119]. In a field trial, Freick et al. [78] compared the efficacy of Startvac® with Bestvac® (IDT, Dessau-Rosslau, Germany) another herd-specific autologous commercial vaccine in a dairy herd with a high prevalence of S. aureus and found that the herd prevalence of S. aureus mastitis was lower in the Startvac® and Bestvac® vaccinated cows compared to the control cows. However, there were no other differences in terms of improvement of udder health. These authors [78] concluded that vaccination with Startvac® and Bestvac® did not improve udder health. In another field efficacy study on Startvac® in the UK, Bradley et al. [75] found that Startvac® vaccinated cows had clinical mastitis with reduced severity and higher milk production compared to non-vaccinated control cows [75].
\nSimilarly, Schukken et al. [77] evaluated effect of Startvac® on the development of new IMI and the duration of infections caused by S. aureus and CNS. These authors [77] found that vaccinated cows had decreased incidence rate and a shorter duration of S. aureus and CNS mastitis. Piepers et al. [76], also tested the efficacy of Startvac® through vaccination and subsequent challenge with a heterologous killed S. aureus strain and found that the inflammatory response in the vaccinated cows was less severe compared to the control cows. These authors [76] suggested that Startvac® elicited a strong Th2 immune response against S. aureus in vaccinated cows and was more effective at clearing bacteria compared to the control cows. Contrary to these observations, Landin et al. [135], evaluated the effects of Startvac® on milk production, udder health, and survival on two Swedish dairy herds with S. aureus mastitis problems and found no significant differences between the Startvac® vaccinated and non-vaccinated control cows on the health parameters they evaluated.
\nAn experimental S. aureus vaccine made up of a combination of plasmids encoding fibronectin-binding motifs of fibronectin-binding protein (FnBP) and clumping factor A (ClfA), and plasmid encoding bovine granulocyte-macrophage-colony stimulatory factor, was used as a vaccine with a subsequent challenge with bacteria to test its protective effects [95]. These authors (Shkreta et al. 2004) found that their experimental vaccine-induced immune responses in the heifers that were partially protective upon experimental challenge [95]. Another controlled experimental vaccine efficacy study was conducted on the slime associated antigenic complex (SAAC) which is an extracellular component of Staphylococcus aureus, as vaccine antigen in which one group of cows were vaccinated with a vaccine containing a low amount of SAAC and another group with a high amount of SAAC and the unvaccinated group served as a control [136]. Upon intramammary infusion (challenge) with S. aureus, no difference in the occurrence of mastitis among all three groups despite the fact that the vaccine with high SAAC content induced higher production of antibodies compared to the vaccine with a low amount of SAAC [136]. Similarly, Pellegrino et al. [137], vaccinated dairy cows with an avirulent mutant strain of S. aureus and subsequently challenged with S. aureus 20 days after the second vaccination which resulted in no significant differences in the number of somatic cell count (SCC) or number of bacteria shedding through milk despite increased IgG antibody titer in the vaccinated cows compared to the control cows.
\nSome of the constraints affecting the successful development of effective mastitis vaccines are strain variation, the presence of exopolysaccharide (capsule, slime, biofilm) layer in most pathogenic strains of bacteria (Staph. aureus, Strep. uberis) which does not allow recognition of antibody-coated bacteria by phagocytic cells, dilution of immune effectors by milk [138, 139], the interaction between milk components and immune effectors [140] that reduce their effectiveness, and the ability of most mastitis-causing bacteria to attach and internalize into mammary epithelial cells. Furthermore, evaluation of mastitis vaccines is complicated by the absence of uniform challenge study models, and lack of uniform route(s) of vaccination, time of vaccination, adjuvants, and challenge dose. There is an increasing need for development of better vaccines that overcome these problems. Most mastitis vaccines are killed whole bacterial cells (Bacterin) vaccines [75, 77, 80, 88, 89, 91, 92, 93, 94, 95, 97, 98, 99] that are difficult to improve because of difficulty to specifically identify an immunogenic component that induced partial or some protective effect. In this regard, some of the current efforts to use a mixture of purified surface proteins as vaccine antigens [100] to induce immunity than killed whole bacterial cells (Bacterin) is encouraging. A better understanding of natural and acquired immunological defenses of the mammary gland coupled with detailed knowledge of the pathogenesis of each mammary pathogen should lead to the development of improved methods of reducing the incidence of mastitis in dairy cows.
\n\nS. uberis is ubiquitous in the cow’s environment accounting for a significant number of mastitis cases. It is found on-farm in water, soil, plant material, bedding, flies, hay, and feces [141]. As such, S. uberis is remarkably adaptable, affecting lactating and dry cows, heifers, and multiparous cows, causing clinical or subclinical mastitis, and even being responsible for persistent colonization without an elevation in the somatic cell count [142, 143]. It has been described as an environmental pathogen [108, 144, 145, 146] with potential as a contagious pathogen [142, 143, 147]. S. uberis has ability to persist within the mammary gland which lead to chronic mastitis that is difficult to treat [148]. Coliform bacteria are a major cause of clinical mastitis [149, 150]. A vaccine that prevents S. uberis mastitis is not available, control measures are limited to the implementation of good management practices. Recently vaccine efficacy trial with extract of biofilm-forming strains of S. uberis (UBAC®) (Hipra, Amir, Spain), was reported to reduce clinical severity [84]. It is not clear what kind of adative immunity is induced by UBAC® S. uberis vaccine [84] and it only conferred partial reduction in clinical severity of mastitis. Multiple intramammary vaccinations of dairy cows with killed S. uberis cells resulted in the complete protection from experimental infection with the homologous strain [103]. Similarly, subcutaneous vaccination of dairy cows with live S. uberis followed by intramammary booster vaccination with S. uberis cell surface extract protected against challenge with the homologous strain but was less effective against a heterologous strain [106]. Vaccination with S. uberis glyceraldehyde phosphate dehydrogenase C (GapC) protein induced immune responses that confer a significant reduction in inflammation post-challenge [107, 151]. The pauA is a plasminogen activator and also binds active protease plasmin [152]. It has been postulated that acquisition of plasmin may promote invasion [153]. Vaccination of dairy cows with PauA induced increased antibody titers that conferred reduction in clinical severity [154]. However, mutation of pauA did not alter ability to grow in milk or to infect lactating bovine mammary glands. It appears that the ability to activate plasminogen through PauA does not play a major role in pathogenesis of S. uberis to either grow in milk or infect bovine mammary gland [155].
\n\nS. uberis expresses several surface associated proteins such as S. uberis adhesion molecule (SUAM) and extracellular matrix binding proteins, which allow it to adhere to and internalize into mammary epithelial cells, successfully inducing IMI [156, 157, 158]. The S. uberis adhesion molecule (SUAM) plays a central role in the adherence of S. uberis to mammary epithelial cells [159, 160, 161, 162]. Vaccination of dairy cows with SUAM induced strong immune resposes in vaccinated cows [163]. The immune serum from SUAM vaccinated cows prevented S. uberis adhesion and invasion into mammary epithelial cells in vitro [163]. In vivo infusion of mammary quarters of dairy cows with S. uberis pre-incubated with immune-serum from SUAM vaccinated cows reduced clinical severity [164]. The SUAM gene deletion mutant strain is less pathogenic to mammary epithelial cells [165] and to dairy cows [159]. Controlled experimental efficacy studies using SUAM as vaccine antigen to control S. uberis mastitis showed that SUAM is immunogenic but the induced immunity was not protective. Following experimental IMI challenge with S. uberis, clinical signs emerged at about 48 h, along with increased levels of inflammatory cytokines including TNF-α, IL-1β, IL-6, and IL-8 in milk at 60 h post-infection [166]. Adaptive immune response cytokines such as IFN-γ promotes a cell-mediated immune response by enhancing functions such as macrophage bacterial killing, antigen presentation, cytotoxic T cell activation, and increased IgG2 levels. The IL-4 expression is associated with the antibody-mediated response, which is generally linked to parasite resistance, allergic reactions, and increased levels of IgG1 [167, 168]. This partial protection by the SUSP vaccine can be improved with dose optimization, appropriate adjuvant, route of injection, and timing of vaccination.
\nIn conclusion, it is clear that Bacterin vaccines have some protective effect against homologous strains, and single surface protein is not effective. Therefore; use of multiple surface proteins may induce better immunity that prevents clinical disease and production losses.
\nColiform bacteria are a major cause of clinical mastitis [149, 150]. Coliforms include the genera Escherichia, Klebsiella, and Enterobacter [169]. Eighty to ninety percent of coliform intramammary infection (IMI) develop clinical mastitis, and 10% will be severe and could lead to death [150]. E. coli usually infects the mammary glands during the dry period and progresses to inflammation and clinical mastitis during the early lactation with local and sometimes severe systemic clinical manifestations.
\nIron is an essential nutrient for the growth of coliforms [170]. However, free iron is limited in the bovine milk because most iron is bound to citrate and to a lesser extent to lactoferrin, transferrin, xanthine oxidase, and some caseins [171] and maintained at concentrations below levels required to support coliform growth [172]. To overcome this limited iron source, coliforms express multiple iron transport systems [173], which include synthesis of siderophores (e.g., enterobactin, aerobactin, ferrichrome) that bind iron with high affinity [174], the expression of iron-regulated outer membrane proteins (IROMP) that binds to ferric siderophore complexes to transport into bacterial cell and enzymes to utlize the chelated iron [173]. The siderophores are too large (600 to 1200 Da) to pass through the porin channels of the bacterial outer membrane [175, 176]. Therefore, the siderophores require specific IROMP to enable their passage across the bacterial outer membrane into the periplasm [177, 178]. The enterobactin is a siderophore with the highest affinity for iron, and it is produced by most pathogenic E. coli and Klebsiella spp. [179, 180, 181]. The aerobactin is another siderophore that was detected in only 12% of E. coli isolated from mastitis cases [182]. Enterobactin is the primary siderophore of Escherichia coli and many other Gram-negative bacteria [183]. Coliform bacteria also developed the ability to take up iron directly from naturally occurring organic iron-binding acids, including citrate [173, 184]. The citrate iron uptake system requires ferric dicitrate for induction [184]. More than 0.1 mM citrate is required for the induction of this system under iron-restricted conditions [184]. The ferric citrate transport system is the major iron acquisition system utilized by E. coli [173] to grow in the mammary gland. The mammary gland is an iron-restricted environment, and bovine milk contains approximately 7 mM citrate [185] which is ideal for induction of ferric citrate transport sytem.
\nFerric enterobactin receptor, FepA, is an 81 kDa iron regulated outer membrane protein (IROMP), that binds to ferric enterobactin complex to transoport iron into the bacterial cell [186, 187]. Vaccination of dairy cows with FepA elicited an increased immunological response in serum and milk [188]. Bovine IgG directed against FepA inhibited the growth of coliform bacteria by interfering with the binding of the ferric enterobactin complex [189]. Ferric citrate receptor, FecA, is an 80.5-kDa IROMP that is responsible for the binding of ferric dicitrate [190] and transport into the bacterial cell. The FecA, is conserved among coliforms isolated from cases of naturally occurring mastitis [191]. The iron-regulated outer membrane proteins, FepA and FecA are ideal vaccine candidates because they are surface exposed, antigenic, and conserved among isolates from IMI.
\nImmunization of dairy cows with FepA induced significantly higher serum and whey anti-FepA IgG titers than in E. coli J5 vaccinates [188]. Results of in vitro growth inhibition studies demonstrated that antibody specific for blocking ferric enterobactin-binding site (anti-FepA) inhibited the growth of E. coli in vitro [192]. Cows immunized with FecA did have increased antibody titers in serum and mammary secretions compared with E. coli J5 immunization and unimmunized control cows [193, 194]. Antibody purified from colostrum inhibited the growth of E. coli when cultured in synthetic media modified to induce FecA expression [193]. Despite their antigenicity, the use of either FepA or FecA alone were not sufficient to prevent mastitis. The FecA and FepA are antigenically distinct [191].
\nIntramammary infection with E. coli induced expression and release of pro-inflammatory cytokines such as TNF-alpha, IL-8, IL-6, and IL-1 [195, 196]. Recently it has been shown with mouse mastitis models that IL-17A and Th17 cells are instrumental in the defense against E. coli IMI [197, 198]. However, the role of IL-17 in bovine E. coli mastitis is not well defined. Results of a recent vaccine efficacy study against E. coli mastitis suggested that cell-mediated immune response has more protective effect than humoral response [199]. The cytokine signaling pathways that lead to efficient bacterial clearance is not clearly defined.
\nThe four coliform vaccines which include 1) J-5 Bacterin® (Zoetis, Kalamazoo, MI) [82, 83], 2) Mastiguard®, 3) J Vac® (Merial-Boehringer Ingelheim vet medical, Inc., Duluth, GA) and 4) Endovac-bovi® (IMMVAC) (Endovac Animal Health, Columbia, MO). Of the four coliform vaccines, J-5 Bacterin® and Mastiguard® are believed to have the same component, which is J5 Bacterin. The J Vac® is a different bacterin-toxoid. The Endovac-Bovi® contains mutant Salmonella typhimurium bacterin toxoid. All coliform mastitis vaccine formulations use gram-negative core antigens to produce non-specific immunity directed against endotoxin (LPS) [119]. The efficacy of these vaccines has been demonstrated in both experimental challenge trials and field trials in commercial dairy herds [109, 110, 111]. The principle of these bacterins is based upon their ability to stimulate the production of antibodies directed against common core antigens that gram-negative bacteria share. These vaccines are considered efficacious even though the rate of intramammary infection is not significantly reduced in vaccinated animals because they significantly reduce the clinical effects of the infection. Experimental challenge studies have demonstrated that J5 vaccines are able to reduce bacterial counts in milk and result in fewer clinical symptoms [109]. Vaccinated cows may become infected with gram-negative mastitis pathogens at the same rate as control animals but have a lower rate of development of clinical mastitis [111], reduced the duration of IMI [110], reduced production, culling, and death losses [200, 201].
\nThere is an increasing need for the development of effective vaccines against major bacterial bovine mastitis pathogens. A better understanding of the natural and acquired immunological defenses of the mammary gland coupled with detailed knowledge of the pathogenesis of each mammary pathogen should lead to the development of improved methods of reducing the incidence of mastitis in dairy cows (Table 1).
\nIn line with the Principles of Transparency and Best Practice in Scholarly Publishing, below is a more detailed description of IntechOpen's Advertising Policy.
",metaTitle:"Advertising Policy",metaDescription:"IntechOpen partners with third-party companies to serve ads and/or collect certain information when you visit our website. These companies may collect non-personally identifiable information (not including your name, address, email address or telephone number) during your visit to IntechOpen's website.",metaKeywords:null,canonicalURL:"/page/advertising-policy",contentRaw:'[{"type":"htmlEditorComponent","content":"1. IntechOpen partners with third-party companies to serve ads and/or collect certain information when you visit our website. These companies may collect non-personally identifiable information (not including your name, address, email address or telephone number) during your visit to IntechOpen's website.
\\n\\n2. All advertisements and commercially sponsored publications are independent from editorial decisions and are linked to reader behaviour.
\\n\\n3. IntechOpen does not endorse any product or service marked as an advertisement on IntechOpen website.
\\n\\n4. IntechOpen has blocked all the inappropriate types of advertising.
\\n\\n5. IntechOpen has blocked advertisement of harmful products or services.
\\n\\n6. Advertisements and editorial content are clearly distinguishable.
\\n\\n7. Editorial decisions will not be influenced by current or potential advertisers and will not be influenced by marketing decisions.
\\n\\n8. Advertisers have no control or influence over the results of searches a user may conduct on the website by keyword or search topic.
\\n\\n9. Please send any complaints about advertising to: info@intechopen.com.
\\n"}]'},components:[{type:"htmlEditorComponent",content:'1. IntechOpen partners with third-party companies to serve ads and/or collect certain information when you visit our website. These companies may collect non-personally identifiable information (not including your name, address, email address or telephone number) during your visit to IntechOpen's website.
\n\n2. All advertisements and commercially sponsored publications are independent from editorial decisions and are linked to reader behaviour.
\n\n3. IntechOpen does not endorse any product or service marked as an advertisement on IntechOpen website.
\n\n4. IntechOpen has blocked all the inappropriate types of advertising.
\n\n5. IntechOpen has blocked advertisement of harmful products or services.
\n\n6. Advertisements and editorial content are clearly distinguishable.
\n\n7. Editorial decisions will not be influenced by current or potential advertisers and will not be influenced by marketing decisions.
\n\n8. Advertisers have no control or influence over the results of searches a user may conduct on the website by keyword or search topic.
\n\n9. Please send any complaints about advertising to: info@intechopen.com.
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. From 2004 to 2011, he was a Research Assistant with the Communications Engineering Department at the University of Málaga. In 2011, he became an Assistant Professor in the same department. From 2012 to 2015, he was with Ericsson Spain, where he was working on geo-location\ntools for third generation mobile networks. Since 2015, he is a Marie-Curie fellow at the Denmark Technical University. His current research interests include the areas of mobile communication systems and channel modeling in addition to atmospheric optical communications, adaptive optics and statistics",institutionString:null,institution:{name:"University of Malaga",country:{name:"Spain"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5766},{group:"region",caption:"Middle and South America",value:2,count:5228},{group:"region",caption:"Africa",value:3,count:1717},{group:"region",caption:"Asia",value:4,count:10370},{group:"region",caption:"Australia and Oceania",value:5,count:897},{group:"region",caption:"Europe",value:6,count:15790}],offset:12,limit:12,total:118192},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{hasNoEditors:"0",sort:"ebgfFaeGuveeFgfcChcyvfu"},books:[],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:16},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:4},{group:"topic",caption:"Business, Management and Economics",value:7,count:1},{group:"topic",caption:"Chemistry",value:8,count:8},{group:"topic",caption:"Computer and Information Science",value:9,count:6},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:7},{group:"topic",caption:"Engineering",value:11,count:16},{group:"topic",caption:"Environmental Sciences",value:12,count:2},{group:"topic",caption:"Immunology and Microbiology",value:13,count:3},{group:"topic",caption:"Materials Science",value:14,count:5},{group:"topic",caption:"Mathematics",value:15,count:1},{group:"topic",caption:"Medicine",value:16,count:24},{group:"topic",caption:"Neuroscience",value:18,count:1},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:3},{group:"topic",caption:"Physics",value:20,count:3},{group:"topic",caption:"Psychology",value:21,count:4},{group:"topic",caption:"Robotics",value:22,count:1},{group:"topic",caption:"Social Sciences",value:23,count:3},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:1}],offset:0,limit:12,total:null},popularBooks:{featuredBooks:[{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9644",title:"Glaciers and the Polar Environment",subtitle:null,isOpenForSubmission:!1,hash:"e8cfdc161794e3753ced54e6ff30873b",slug:"glaciers-and-the-polar-environment",bookSignature:"Masaki Kanao, Danilo Godone and Niccolò Dematteis",coverURL:"https://cdn.intechopen.com/books/images_new/9644.jpg",editors:[{id:"51959",title:"Dr.",name:"Masaki",middleName:null,surname:"Kanao",slug:"masaki-kanao",fullName:"Masaki Kanao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8985",title:"Natural Resources Management and Biological Sciences",subtitle:null,isOpenForSubmission:!1,hash:"5c2e219a6c021a40b5a20c041dea88c4",slug:"natural-resources-management-and-biological-sciences",bookSignature:"Edward R. Rhodes and Humood Naser",coverURL:"https://cdn.intechopen.com/books/images_new/8985.jpg",editors:[{id:"280886",title:"Prof.",name:"Edward R",middleName:null,surname:"Rhodes",slug:"edward-r-rhodes",fullName:"Edward R Rhodes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9671",title:"Macrophages",subtitle:null,isOpenForSubmission:!1,hash:"03b00fdc5f24b71d1ecdfd75076bfde6",slug:"macrophages",bookSignature:"Hridayesh Prakash",coverURL:"https://cdn.intechopen.com/books/images_new/9671.jpg",editors:[{id:"287184",title:"Dr.",name:"Hridayesh",middleName:null,surname:"Prakash",slug:"hridayesh-prakash",fullName:"Hridayesh Prakash"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9313",title:"Clay Science and Technology",subtitle:null,isOpenForSubmission:!1,hash:"6fa7e70396ff10620e032bb6cfa6fb72",slug:"clay-science-and-technology",bookSignature:"Gustavo Morari Do Nascimento",coverURL:"https://cdn.intechopen.com/books/images_new/9313.jpg",editors:[{id:"7153",title:"Prof.",name:"Gustavo",middleName:null,surname:"Morari Do Nascimento",slug:"gustavo-morari-do-nascimento",fullName:"Gustavo Morari Do Nascimento"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9888",title:"Nuclear Power Plants",subtitle:"The Processes from the Cradle to the Grave",isOpenForSubmission:!1,hash:"c2c8773e586f62155ab8221ebb72a849",slug:"nuclear-power-plants-the-processes-from-the-cradle-to-the-grave",bookSignature:"Nasser Awwad",coverURL:"https://cdn.intechopen.com/books/images_new/9888.jpg",editors:[{id:"145209",title:"Prof.",name:"Nasser",middleName:"S",surname:"Awwad",slug:"nasser-awwad",fullName:"Nasser Awwad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9027",title:"Human Blood Group Systems and Haemoglobinopathies",subtitle:null,isOpenForSubmission:!1,hash:"d00d8e40b11cfb2547d1122866531c7e",slug:"human-blood-group-systems-and-haemoglobinopathies",bookSignature:"Osaro Erhabor and Anjana Munshi",coverURL:"https://cdn.intechopen.com/books/images_new/9027.jpg",editors:[{id:"35140",title:null,name:"Osaro",middleName:null,surname:"Erhabor",slug:"osaro-erhabor",fullName:"Osaro Erhabor"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7841",title:"New Insights Into Metabolic Syndrome",subtitle:null,isOpenForSubmission:!1,hash:"ef5accfac9772b9e2c9eff884f085510",slug:"new-insights-into-metabolic-syndrome",bookSignature:"Akikazu Takada",coverURL:"https://cdn.intechopen.com/books/images_new/7841.jpg",editors:[{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8558",title:"Aerodynamics",subtitle:null,isOpenForSubmission:!1,hash:"db7263fc198dfb539073ba0260a7f1aa",slug:"aerodynamics",bookSignature:"Mofid Gorji-Bandpy and Aly-Mousaad Aly",coverURL:"https://cdn.intechopen.com/books/images_new/8558.jpg",editors:[{id:"35542",title:"Prof.",name:"Mofid",middleName:null,surname:"Gorji-Bandpy",slug:"mofid-gorji-bandpy",fullName:"Mofid Gorji-Bandpy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7847",title:"Medical Toxicology",subtitle:null,isOpenForSubmission:!1,hash:"db9b65bea093de17a0855a1b27046247",slug:"medical-toxicology",bookSignature:"Pınar Erkekoglu and Tomohisa Ogawa",coverURL:"https://cdn.intechopen.com/books/images_new/7847.jpg",editors:[{id:"109978",title:"Prof.",name:"Pınar",middleName:null,surname:"Erkekoglu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10432",title:"Casting Processes and Modelling of Metallic Materials",subtitle:null,isOpenForSubmission:!1,hash:"2c5c9df938666bf5d1797727db203a6d",slug:"casting-processes-and-modelling-of-metallic-materials",bookSignature:"Zakaria Abdallah and Nada Aldoumani",coverURL:"https://cdn.intechopen.com/books/images_new/10432.jpg",editors:[{id:"201670",title:"Dr.",name:"Zak",middleName:null,surname:"Abdallah",slug:"zak-abdallah",fullName:"Zak Abdallah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:5238},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9644",title:"Glaciers and the Polar Environment",subtitle:null,isOpenForSubmission:!1,hash:"e8cfdc161794e3753ced54e6ff30873b",slug:"glaciers-and-the-polar-environment",bookSignature:"Masaki Kanao, Danilo Godone and Niccolò Dematteis",coverURL:"https://cdn.intechopen.com/books/images_new/9644.jpg",editors:[{id:"51959",title:"Dr.",name:"Masaki",middleName:null,surname:"Kanao",slug:"masaki-kanao",fullName:"Masaki Kanao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8985",title:"Natural Resources Management and Biological Sciences",subtitle:null,isOpenForSubmission:!1,hash:"5c2e219a6c021a40b5a20c041dea88c4",slug:"natural-resources-management-and-biological-sciences",bookSignature:"Edward R. Rhodes and Humood Naser",coverURL:"https://cdn.intechopen.com/books/images_new/8985.jpg",editors:[{id:"280886",title:"Prof.",name:"Edward R",middleName:null,surname:"Rhodes",slug:"edward-r-rhodes",fullName:"Edward R Rhodes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9671",title:"Macrophages",subtitle:null,isOpenForSubmission:!1,hash:"03b00fdc5f24b71d1ecdfd75076bfde6",slug:"macrophages",bookSignature:"Hridayesh Prakash",coverURL:"https://cdn.intechopen.com/books/images_new/9671.jpg",editors:[{id:"287184",title:"Dr.",name:"Hridayesh",middleName:null,surname:"Prakash",slug:"hridayesh-prakash",fullName:"Hridayesh Prakash"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9313",title:"Clay Science and Technology",subtitle:null,isOpenForSubmission:!1,hash:"6fa7e70396ff10620e032bb6cfa6fb72",slug:"clay-science-and-technology",bookSignature:"Gustavo Morari Do Nascimento",coverURL:"https://cdn.intechopen.com/books/images_new/9313.jpg",editors:[{id:"7153",title:"Prof.",name:"Gustavo",middleName:null,surname:"Morari Do Nascimento",slug:"gustavo-morari-do-nascimento",fullName:"Gustavo Morari Do Nascimento"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9888",title:"Nuclear Power Plants",subtitle:"The Processes from the Cradle to the Grave",isOpenForSubmission:!1,hash:"c2c8773e586f62155ab8221ebb72a849",slug:"nuclear-power-plants-the-processes-from-the-cradle-to-the-grave",bookSignature:"Nasser Awwad",coverURL:"https://cdn.intechopen.com/books/images_new/9888.jpg",editors:[{id:"145209",title:"Prof.",name:"Nasser",middleName:"S",surname:"Awwad",slug:"nasser-awwad",fullName:"Nasser Awwad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9027",title:"Human Blood Group Systems and Haemoglobinopathies",subtitle:null,isOpenForSubmission:!1,hash:"d00d8e40b11cfb2547d1122866531c7e",slug:"human-blood-group-systems-and-haemoglobinopathies",bookSignature:"Osaro Erhabor and Anjana Munshi",coverURL:"https://cdn.intechopen.com/books/images_new/9027.jpg",editors:[{id:"35140",title:null,name:"Osaro",middleName:null,surname:"Erhabor",slug:"osaro-erhabor",fullName:"Osaro Erhabor"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10432",title:"Casting Processes and Modelling of Metallic Materials",subtitle:null,isOpenForSubmission:!1,hash:"2c5c9df938666bf5d1797727db203a6d",slug:"casting-processes-and-modelling-of-metallic-materials",bookSignature:"Zakaria Abdallah and Nada Aldoumani",coverURL:"https://cdn.intechopen.com/books/images_new/10432.jpg",editors:[{id:"201670",title:"Dr.",name:"Zak",middleName:null,surname:"Abdallah",slug:"zak-abdallah",fullName:"Zak Abdallah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7841",title:"New Insights Into Metabolic Syndrome",subtitle:null,isOpenForSubmission:!1,hash:"ef5accfac9772b9e2c9eff884f085510",slug:"new-insights-into-metabolic-syndrome",bookSignature:"Akikazu Takada",coverURL:"https://cdn.intechopen.com/books/images_new/7841.jpg",editors:[{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"9550",title:"Entrepreneurship",subtitle:"Contemporary Issues",isOpenForSubmission:!1,hash:"9b4ac1ee5b743abf6f88495452b1e5e7",slug:"entrepreneurship-contemporary-issues",bookSignature:"Mladen Turuk",coverURL:"https://cdn.intechopen.com/books/images_new/9550.jpg",editedByType:"Edited by",editors:[{id:"319755",title:"Prof.",name:"Mladen",middleName:null,surname:"Turuk",slug:"mladen-turuk",fullName:"Mladen Turuk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editedByType:"Edited by",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9313",title:"Clay Science and Technology",subtitle:null,isOpenForSubmission:!1,hash:"6fa7e70396ff10620e032bb6cfa6fb72",slug:"clay-science-and-technology",bookSignature:"Gustavo Morari Do Nascimento",coverURL:"https://cdn.intechopen.com/books/images_new/9313.jpg",editedByType:"Edited by",editors:[{id:"7153",title:"Prof.",name:"Gustavo",middleName:null,surname:"Morari Do Nascimento",slug:"gustavo-morari-do-nascimento",fullName:"Gustavo Morari Do Nascimento"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9888",title:"Nuclear Power Plants",subtitle:"The Processes from the Cradle to the Grave",isOpenForSubmission:!1,hash:"c2c8773e586f62155ab8221ebb72a849",slug:"nuclear-power-plants-the-processes-from-the-cradle-to-the-grave",bookSignature:"Nasser Awwad",coverURL:"https://cdn.intechopen.com/books/images_new/9888.jpg",editedByType:"Edited by",editors:[{id:"145209",title:"Prof.",name:"Nasser",middleName:"S",surname:"Awwad",slug:"nasser-awwad",fullName:"Nasser Awwad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8098",title:"Resources of Water",subtitle:null,isOpenForSubmission:!1,hash:"d251652996624d932ef7b8ed62cf7cfc",slug:"resources-of-water",bookSignature:"Prathna Thanjavur Chandrasekaran, Muhammad Salik Javaid, Aftab Sadiq",coverURL:"https://cdn.intechopen.com/books/images_new/8098.jpg",editedByType:"Edited by",editors:[{id:"167917",title:"Dr.",name:"Prathna",middleName:null,surname:"Thanjavur Chandrasekaran",slug:"prathna-thanjavur-chandrasekaran",fullName:"Prathna Thanjavur Chandrasekaran"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9644",title:"Glaciers and the Polar Environment",subtitle:null,isOpenForSubmission:!1,hash:"e8cfdc161794e3753ced54e6ff30873b",slug:"glaciers-and-the-polar-environment",bookSignature:"Masaki Kanao, Danilo Godone and Niccolò Dematteis",coverURL:"https://cdn.intechopen.com/books/images_new/9644.jpg",editedByType:"Edited by",editors:[{id:"51959",title:"Dr.",name:"Masaki",middleName:null,surname:"Kanao",slug:"masaki-kanao",fullName:"Masaki Kanao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10432",title:"Casting Processes and Modelling of Metallic Materials",subtitle:null,isOpenForSubmission:!1,hash:"2c5c9df938666bf5d1797727db203a6d",slug:"casting-processes-and-modelling-of-metallic-materials",bookSignature:"Zakaria Abdallah and Nada Aldoumani",coverURL:"https://cdn.intechopen.com/books/images_new/10432.jpg",editedByType:"Edited by",editors:[{id:"201670",title:"Dr.",name:"Zak",middleName:null,surname:"Abdallah",slug:"zak-abdallah",fullName:"Zak Abdallah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9671",title:"Macrophages",subtitle:null,isOpenForSubmission:!1,hash:"03b00fdc5f24b71d1ecdfd75076bfde6",slug:"macrophages",bookSignature:"Hridayesh Prakash",coverURL:"https://cdn.intechopen.com/books/images_new/9671.jpg",editedByType:"Edited by",editors:[{id:"287184",title:"Dr.",name:"Hridayesh",middleName:null,surname:"Prakash",slug:"hridayesh-prakash",fullName:"Hridayesh Prakash"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8415",title:"Extremophilic Microbes and Metabolites",subtitle:"Diversity, Bioprospecting and Biotechnological Applications",isOpenForSubmission:!1,hash:"93e0321bc93b89ff73730157738f8f97",slug:"extremophilic-microbes-and-metabolites-diversity-bioprospecting-and-biotechnological-applications",bookSignature:"Afef Najjari, Ameur Cherif, Haïtham Sghaier and Hadda Imene Ouzari",coverURL:"https://cdn.intechopen.com/books/images_new/8415.jpg",editedByType:"Edited by",editors:[{id:"196823",title:"Dr.",name:"Afef",middleName:null,surname:"Najjari",slug:"afef-najjari",fullName:"Afef Najjari"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9731",title:"Oxidoreductase",subtitle:null,isOpenForSubmission:!1,hash:"852e6f862c85fc3adecdbaf822e64e6e",slug:"oxidoreductase",bookSignature:"Mahmoud Ahmed Mansour",coverURL:"https://cdn.intechopen.com/books/images_new/9731.jpg",editedByType:"Edited by",editors:[{id:"224662",title:"Prof.",name:"Mahmoud Ahmed",middleName:null,surname:"Mansour",slug:"mahmoud-ahmed-mansour",fullName:"Mahmoud Ahmed Mansour"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"991",title:"Herbalism",slug:"herbalism",parent:{title:"Complementary Medicine",slug:"complementary-medicine"},numberOfBooks:9,numberOfAuthorsAndEditors:316,numberOfWosCitations:228,numberOfCrossrefCitations:119,numberOfDimensionsCitations:354,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"herbalism",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"6994",title:"Tea",subtitle:"Chemistry and Pharmacology",isOpenForSubmission:!1,hash:"e6241cd52834161ac64d4a7b2a812796",slug:"tea-chemistry-and-pharmacology",bookSignature:"Gonçalo Justino",coverURL:"https://cdn.intechopen.com/books/images_new/6994.jpg",editedByType:"Edited by",editors:[{id:"76687",title:"Dr.",name:"Gonçalo",middleName:null,surname:"Justino",slug:"goncalo-justino",fullName:"Gonçalo Justino"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9108",title:"Medicinal Plants",subtitle:"Use in Prevention and Treatment of Diseases",isOpenForSubmission:!1,hash:"7d0c52af195da3322be63610d6567019",slug:"medicinal-plants-use-in-prevention-and-treatment-of-diseases",bookSignature:"Bassam Abdul Rasool Hassan",coverURL:"https://cdn.intechopen.com/books/images_new/9108.jpg",editedByType:"Edited by",editors:[{id:"155124",title:"Dr.",name:"Bassam",middleName:"Abdul Rasool",surname:"Hassan",slug:"bassam-hassan",fullName:"Bassam Hassan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6302",title:"Herbal Medicine",subtitle:null,isOpenForSubmission:!1,hash:"b70a98c6748d0449a6288de73da7b8d9",slug:"herbal-medicine",bookSignature:"Philip F. Builders",coverURL:"https://cdn.intechopen.com/books/images_new/6302.jpg",editedByType:"Edited by",editors:[{id:"182744",title:"Dr.",name:"Philip",middleName:null,surname:"Builders",slug:"philip-builders",fullName:"Philip Builders"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5612",title:"Aromatic and Medicinal Plants",subtitle:"Back to Nature",isOpenForSubmission:!1,hash:"ccf7987200bfc541e2e56bb138de86f3",slug:"aromatic-and-medicinal-plants-back-to-nature",bookSignature:"Hany A. El-Shemy",coverURL:"https://cdn.intechopen.com/books/images_new/5612.jpg",editedByType:"Edited by",editors:[{id:"54719",title:"Prof.",name:"Hany",middleName:null,surname:"El-Shemy",slug:"hany-el-shemy",fullName:"Hany El-Shemy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5494",title:"Chinese Medical Therapies for Diabetes, Infertility, Silicosis and the Theoretical Basis",subtitle:null,isOpenForSubmission:!1,hash:"7b3b6a2700d7fd0511770bf77290a422",slug:"chinese-medical-therapies-for-diabetes-infertility-silicosis-and-the-theoretical-basis",bookSignature:"Xing-Tai Li",coverURL:"https://cdn.intechopen.com/books/images_new/5494.jpg",editedByType:"Edited by",editors:[{id:"73821",title:"Dr.",name:"Xing-Tai",middleName:null,surname:"Li",slug:"xing-tai-li",fullName:"Xing-Tai Li"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2975",title:"Complementary Therapies for the Contemporary Healthcare",subtitle:null,isOpenForSubmission:!1,hash:"604c4ba43197c3ba1506c55c763d4ca7",slug:"complementary-therapies-for-the-contemporary-healthcare",bookSignature:"Marcelo Saad and Roberta de Medeiros",coverURL:"https://cdn.intechopen.com/books/images_new/2975.jpg",editedByType:"Edited by",editors:[{id:"51991",title:"Prof.",name:"Marcelo",middleName:null,surname:"Saad",slug:"marcelo-saad",fullName:"Marcelo Saad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"542",title:"A Compendium of Essays on Alternative Therapy",subtitle:null,isOpenForSubmission:!1,hash:"a805c1d2d8449dcecd52eb7a48d2e6b1",slug:"a-compendium-of-essays-on-alternative-therapy",bookSignature:"Arup Bhattacharya",coverURL:"https://cdn.intechopen.com/books/images_new/542.jpg",editedByType:"Edited by",editors:[{id:"66982",title:"Dr.",name:"Arup",middleName:null,surname:"Bhattacharya",slug:"arup-bhattacharya",fullName:"Arup Bhattacharya"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"643",title:"Recent Advances in Theories and Practice of Chinese Medicine",subtitle:null,isOpenForSubmission:!1,hash:"499a7fabf489d2502de4616a4c7f3da0",slug:"recent-advances-in-theories-and-practice-of-chinese-medicine",bookSignature:"Haixue Kuang",coverURL:"https://cdn.intechopen.com/books/images_new/643.jpg",editedByType:"Edited by",editors:[{id:"44740",title:"Prof.",name:"Haixue",middleName:null,surname:"Kuang",slug:"haixue-kuang",fullName:"Haixue Kuang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"631",title:"Quality Control of Herbal Medicines and Related Areas",subtitle:null,isOpenForSubmission:!1,hash:"5ced81d454b4a5ded2a0aa02e0d7621d",slug:"quality-control-of-herbal-medicines-and-related-areas",bookSignature:"Yukihiro Shoyama",coverURL:"https://cdn.intechopen.com/books/images_new/631.jpg",editedByType:"Edited by",editors:[{id:"35812",title:"Prof.",name:"Yukihiro",middleName:null,surname:"Shoyama",slug:"yukihiro-shoyama",fullName:"Yukihiro Shoyama"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:9,mostCitedChapters:[{id:"61866",doi:"10.5772/intechopen.76139",title:"Plants Secondary Metabolites: The Key Drivers of the Pharmacological Actions of Medicinal Plants",slug:"plants-secondary-metabolites-the-key-drivers-of-the-pharmacological-actions-of-medicinal-plants",totalDownloads:5517,totalCrossrefCites:13,totalDimensionsCites:32,book:{slug:"herbal-medicine",title:"Herbal Medicine",fullTitle:"Herbal Medicine"},signatures:"Rehab A. Hussein and Amira A. El-Anssary",authors:[{id:"212117",title:"Dr.",name:"Rehab",middleName:null,surname:"Hussein",slug:"rehab-hussein",fullName:"Rehab Hussein"},{id:"221140",title:"Dr.",name:"Amira",middleName:null,surname:"El-Anssary",slug:"amira-el-anssary",fullName:"Amira El-Anssary"}]},{id:"54028",doi:"10.5772/67291",title:"Chemical Composition and Biological Activities of Mentha Species",slug:"chemical-composition-and-biological-activities-of-mentha-species",totalDownloads:6007,totalCrossrefCites:5,totalDimensionsCites:25,book:{slug:"aromatic-and-medicinal-plants-back-to-nature",title:"Aromatic and Medicinal Plants",fullTitle:"Aromatic and Medicinal Plants - Back to Nature"},signatures:"Fatiha Brahmi, Madani Khodir, Chibane Mohamed and Duez Pierre",authors:[{id:"193281",title:"Dr.",name:"Fatiha",middleName:null,surname:"Brahmi",slug:"fatiha-brahmi",fullName:"Fatiha Brahmi"},{id:"199693",title:"Prof.",name:"Khodir",middleName:null,surname:"Madani",slug:"khodir-madani",fullName:"Khodir Madani"},{id:"199694",title:"Prof.",name:"Pierre",middleName:null,surname:"Duez",slug:"pierre-duez",fullName:"Pierre Duez"},{id:"203738",title:"Prof.",name:"Mohamed",middleName:null,surname:"Chibane",slug:"mohamed-chibane",fullName:"Mohamed Chibane"}]},{id:"26496",doi:"10.5772/28488",title:"Potential Genotoxic and Cytotoxic Effects of Plant Extracts",slug:"potential-genotoxic-and-cytotoxic-effects-of-plant-extracts",totalDownloads:8345,totalCrossrefCites:0,totalDimensionsCites:16,book:{slug:"a-compendium-of-essays-on-alternative-therapy",title:"A Compendium of Essays on Alternative Therapy",fullTitle:"A Compendium of Essays on Alternative Therapy"},signatures:"Tülay Askin Celik",authors:[{id:"74041",title:"Dr.",name:"Tulay",middleName:null,surname:"Askin Celik",slug:"tulay-askin-celik",fullName:"Tulay Askin Celik"}]}],mostDownloadedChaptersLast30Days:[{id:"64851",title:"Herbal Medicines in African Traditional Medicine",slug:"herbal-medicines-in-african-traditional-medicine",totalDownloads:9890,totalCrossrefCites:10,totalDimensionsCites:16,book:{slug:"herbal-medicine",title:"Herbal Medicine",fullTitle:"Herbal Medicine"},signatures:"Ezekwesili-Ofili Josephine Ozioma and Okaka Antoinette Nwamaka\nChinwe",authors:[{id:"191264",title:"Prof.",name:"Josephine",middleName:"Ozioma",surname:"Ezekwesili-Ofili",slug:"josephine-ezekwesili-ofili",fullName:"Josephine Ezekwesili-Ofili"},{id:"211585",title:"Prof.",name:"Antoinette",middleName:null,surname:"Okaka",slug:"antoinette-okaka",fullName:"Antoinette Okaka"}]},{id:"61866",title:"Plants Secondary Metabolites: The Key Drivers of the Pharmacological Actions of Medicinal Plants",slug:"plants-secondary-metabolites-the-key-drivers-of-the-pharmacological-actions-of-medicinal-plants",totalDownloads:5498,totalCrossrefCites:13,totalDimensionsCites:32,book:{slug:"herbal-medicine",title:"Herbal Medicine",fullTitle:"Herbal Medicine"},signatures:"Rehab A. Hussein and Amira A. El-Anssary",authors:[{id:"212117",title:"Dr.",name:"Rehab",middleName:null,surname:"Hussein",slug:"rehab-hussein",fullName:"Rehab Hussein"},{id:"221140",title:"Dr.",name:"Amira",middleName:null,surname:"El-Anssary",slug:"amira-el-anssary",fullName:"Amira El-Anssary"}]},{id:"54028",title:"Chemical Composition and Biological Activities of Mentha Species",slug:"chemical-composition-and-biological-activities-of-mentha-species",totalDownloads:6003,totalCrossrefCites:5,totalDimensionsCites:25,book:{slug:"aromatic-and-medicinal-plants-back-to-nature",title:"Aromatic and Medicinal Plants",fullTitle:"Aromatic and Medicinal Plants - Back to Nature"},signatures:"Fatiha Brahmi, Madani Khodir, Chibane Mohamed and Duez Pierre",authors:[{id:"193281",title:"Dr.",name:"Fatiha",middleName:null,surname:"Brahmi",slug:"fatiha-brahmi",fullName:"Fatiha Brahmi"},{id:"199693",title:"Prof.",name:"Khodir",middleName:null,surname:"Madani",slug:"khodir-madani",fullName:"Khodir Madani"},{id:"199694",title:"Prof.",name:"Pierre",middleName:null,surname:"Duez",slug:"pierre-duez",fullName:"Pierre Duez"},{id:"203738",title:"Prof.",name:"Mohamed",middleName:null,surname:"Chibane",slug:"mohamed-chibane",fullName:"Mohamed Chibane"}]},{id:"53301",title:"From Medicinal Plant Raw Material to Herbal Remedies",slug:"from-medicinal-plant-raw-material-to-herbal-remedies",totalDownloads:3604,totalCrossrefCites:1,totalDimensionsCites:4,book:{slug:"aromatic-and-medicinal-plants-back-to-nature",title:"Aromatic and Medicinal Plants",fullTitle:"Aromatic and Medicinal Plants - Back to Nature"},signatures:"Sofija M. Djordjevic",authors:[{id:"84281",title:"Dr.",name:"Sofija",middleName:null,surname:"Djordjevic",slug:"sofija-djordjevic",fullName:"Sofija Djordjevic"}]},{id:"70638",title:"Medicinal Plants Having Antifungal Properties",slug:"medicinal-plants-having-antifungal-properties",totalDownloads:644,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"medicinal-plants-use-in-prevention-and-treatment-of-diseases",title:"Medicinal Plants",fullTitle:"Medicinal Plants - Use in Prevention and Treatment of Diseases"},signatures:"Koushlesh Kumar Mishra, Chanchal Deep Kaur, Anil Kumar Sahu, Rajnikant Panik, Pankaj Kashyap, Saraswati Prasad Mishra and Shweta Dutta",authors:[{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Sahu",slug:"anil-sahu",fullName:"Anil Sahu"},{id:"211230",title:"Mr.",name:"Pankaj",middleName:null,surname:"Kashyap",slug:"pankaj-kashyap",fullName:"Pankaj Kashyap"},{id:"221419",title:"Mr.",name:"Koushlesh",middleName:null,surname:"Mishra",slug:"koushlesh-mishra",fullName:"Koushlesh Mishra"},{id:"221420",title:"Mr.",name:"Sarawati Prasad",middleName:null,surname:"Mishra",slug:"sarawati-prasad-mishra",fullName:"Sarawati Prasad Mishra"},{id:"270359",title:"Dr.",name:"Chanchal Deep",middleName:null,surname:"Kaur",slug:"chanchal-deep-kaur",fullName:"Chanchal Deep Kaur"},{id:"314683",title:"Dr.",name:"Rajnikant",middleName:null,surname:"Panik",slug:"rajnikant-panik",fullName:"Rajnikant Panik"},{id:"314684",title:"Ms.",name:"Shweta",middleName:null,surname:"Dutta",slug:"shweta-dutta",fullName:"Shweta Dutta"}]},{id:"53014",title:"Cardiac Glycosides in Medicinal Plants",slug:"cardiac-glycosides-in-medicinal-plants",totalDownloads:4678,totalCrossrefCites:7,totalDimensionsCites:8,book:{slug:"aromatic-and-medicinal-plants-back-to-nature",title:"Aromatic and Medicinal Plants",fullTitle:"Aromatic and Medicinal Plants - Back to Nature"},signatures:"Nagy Morsy",authors:[{id:"193379",title:"Dr.",name:"Nagy",middleName:null,surname:"Morsy",slug:"nagy-morsy",fullName:"Nagy Morsy"}]},{id:"58270",title:"Toxicity and Safety Implications of Herbal Medicines Used in Africa",slug:"toxicity-and-safety-implications-of-herbal-medicines-used-in-africa",totalDownloads:2173,totalCrossrefCites:3,totalDimensionsCites:8,book:{slug:"herbal-medicine",title:"Herbal Medicine",fullTitle:"Herbal Medicine"},signatures:"Merlin L.K. Mensah, Gustav Komlaga, Arnold D. Forkuo, Caleb\nFirempong, Alexander K. Anning and Rita A. Dickson",authors:[{id:"190435",title:"Dr.",name:"Caleb",middleName:null,surname:"Firempong",slug:"caleb-firempong",fullName:"Caleb Firempong"},{id:"212111",title:"Dr.",name:"Gustav",middleName:null,surname:"Komlaga",slug:"gustav-komlaga",fullName:"Gustav Komlaga"},{id:"217045",title:"Dr.",name:"Arnold Forkuo",middleName:null,surname:"Donkor",slug:"arnold-forkuo-donkor",fullName:"Arnold Forkuo Donkor"},{id:"217049",title:"Prof.",name:"Merlin Lincoln Kwao",middleName:null,surname:"Mensah",slug:"merlin-lincoln-kwao-mensah",fullName:"Merlin Lincoln Kwao Mensah"},{id:"217488",title:"Dr.",name:"Alexander K.",middleName:null,surname:"Anning",slug:"alexander-k.-anning",fullName:"Alexander K. Anning"},{id:"223959",title:"Prof.",name:"Akosua Rita",middleName:null,surname:"Dickson",slug:"akosua-rita-dickson",fullName:"Akosua Rita Dickson"}]},{id:"62180",title:"Introductory Chapter: Introduction to Herbal Medicine",slug:"introductory-chapter-introduction-to-herbal-medicine",totalDownloads:1355,totalCrossrefCites:2,totalDimensionsCites:3,book:{slug:"herbal-medicine",title:"Herbal Medicine",fullTitle:"Herbal Medicine"},signatures:"Philip F. Builders",authors:[{id:"182744",title:"Dr.",name:"Philip",middleName:null,surname:"Builders",slug:"philip-builders",fullName:"Philip Builders"}]},{id:"70593",title:"Herbal Remedies for Breast Cancer Prevention and Treatment",slug:"herbal-remedies-for-breast-cancer-prevention-and-treatment",totalDownloads:708,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"medicinal-plants-use-in-prevention-and-treatment-of-diseases",title:"Medicinal Plants",fullTitle:"Medicinal Plants - Use in Prevention and Treatment of Diseases"},signatures:"Yahyea Baktiar Laskar, Romen Meitei Lourembam and Pranab Behari Mazumder",authors:[{id:"304193",title:"Ph.D. Student",name:"Yahyea",middleName:"Baktiar",surname:"Laskar",slug:"yahyea-laskar",fullName:"Yahyea Laskar"},{id:"309357",title:"Prof.",name:"Pranab Behari",middleName:null,surname:"Mazumder",slug:"pranab-behari-mazumder",fullName:"Pranab Behari Mazumder"}]},{id:"59484",title:"Herbal Medicine",slug:"herbal-medicine",totalDownloads:1357,totalCrossrefCites:2,totalDimensionsCites:2,book:{slug:"herbal-medicine",title:"Herbal Medicine",fullTitle:"Herbal Medicine"},signatures:"Nontokozo Z. Msomi and Mthokozisi B.C. Simelane",authors:[{id:"193091",title:"Dr.",name:"Mthokozisi",middleName:null,surname:"Simelane",slug:"mthokozisi-simelane",fullName:"Mthokozisi Simelane"},{id:"195504",title:"Ms.",name:"Nontokozo",middleName:null,surname:"Msomi",slug:"nontokozo-msomi",fullName:"Nontokozo Msomi"}]}],onlineFirstChaptersFilter:{topicSlug:"herbalism",limit:3,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[{type:"book",id:"10176",title:"Microgrids and Local Energy Systems",subtitle:null,isOpenForSubmission:!0,hash:"c32b4a5351a88f263074b0d0ca813a9c",slug:null,bookSignature:"Prof. Nick Jenkins",coverURL:"https://cdn.intechopen.com/books/images_new/10176.jpg",editedByType:null,editors:[{id:"55219",title:"Prof.",name:"Nick",middleName:null,surname:"Jenkins",slug:"nick-jenkins",fullName:"Nick Jenkins"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:8,limit:8,total:1},route:{name:"chapter.detail",path:"/books/frontiers-in-guided-wave-optics-and-optoelectronics/radio-over-fibre-techniques-and-performance",hash:"",query:{},params:{book:"frontiers-in-guided-wave-optics-and-optoelectronics",chapter:"radio-over-fibre-techniques-and-performance"},fullPath:"/books/frontiers-in-guided-wave-optics-and-optoelectronics/radio-over-fibre-techniques-and-performance",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)}()