\r\n\tRadiation monitoring deals with the sampling and measurement of different products found in different radiation pathways from the environment ending with consumption in humans. Gamma-spectroscopy is the main tool for measurement of these radiations.
\r\n
\r\n\tThe aim of this book is to investigate the radionuclide concentrations in the most consumable food products, air, water and soil. Particularly, it is essential to investigate the radiations level in the surroundings of a nuclear facility.
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\n
1. Introduction
\n
Wearable technologies are becoming increasingly popular as personal health system, enabling continuous real-time monitoring of human health on a daily basis and outside clinical environments [1, 2, 3]. The wearable device market is currently having a worldwide profit of around $34 billion and is expected to reach above $50 billion by 2022 owing to wearables’ ease of use, flexibility, and convenience [4]. Real-time monitoring, operational efficiency, and fitness tracking are reported as main factors supporting the market growth of health wearable devices such as smart watches, smart glasses, and other wellness gadgets, with expected $12.1 billion world market by 2021 [5].
\n
In the past decade, the recent progress in developing wearable devices was more focused on monitoring physical parameters, such as motion, respiration rate, etc. [3, 6, 7]. Today, there is a great interest in evolving wearable sensors capable of detecting chemical markers relevant to the status of health. Different approaches have been applied by researchers to design and fabricate wearable biosensors for remote monitoring of metabolites and electrolytes in body fluids including tear, sweat, and saliva [3, 8, 9, 10]. A great example would be the development of small and reliable sensors that would allow continuous glucose monitoring in diabetic patients [11, 12]. Diabetes is a chronic disease that can significantly impact on quality of life and reduce life expectancy. However, diabetics can stay one step ahead of the disease by monitoring their blood glucose level to minimize the complication of the disease by proper administration of insulin. Currently, blood analysis is the gold standard method for measuring the level of glucose in patient’s blood. However, this technique cannot be applied without penetrating the skin, which can be painful and inconvenient, and requires user obedience. Therefore, current research focuses on the development of portable and wearable devices capable of continuous glucose sensing through noninvasive detection techniques.
\n
\n
\n
2. Tear analysis
\n
A majority of the recent studies in this field have targeted the area of personalized medicine, endeavoring to develop miniaturized wearable devices featuring real-time glucose monitoring in diabetic patients [12, 13, 14, 15]. One great example is contact lens which is an ideal wearable device that can be worn for hours without any pain or discomfort [16]. Integration of glucose biosensors into contact lenses has recently been demonstrated by several research groups [9, 17, 18]. However, the level of glucose in tear fluid is very low (0.1–0.6 mM), requiring a high sensitivity of the sensor for picking up the signal from expected chemical reaction [3, 19]. Yao et al. [16] have fabricated a contact lens with integrated sensor for continuous tear glucose monitoring with wireless communication system over a distance of several centimeters. The sensor demonstrated a fast response of 20 s with a minimum detection of less than 0.01 mM glucose, which is 10–60 times lower than glucose level in human tear [16].
\n
In addition to glucose, lactate is an important metabolite in the human body, which gets converted into l-lactate under hypoxic condition [20]. l-Lactate levels in tear fluid is about 1–5 mmol L−1, which might increase significantly due to some heath conditions including ischemia, inadequate tissue oxygenation, stroke, and different types of cancer [21]. Thomas et al. [22] demonstrated an invasive detection of lactate in human tear by integrating an amperometric lactate sensor with Pt working (WE) and reference (RE) electrodes as well as a counter electrode (CE) as current drain, on a polymer-based contact lens, measuring lactate in situ in human tears without any need for physical sampling [22].
\n
Very recently, Park et al. [17] reported a novel approach for fabricating fully transparent and stretchable smart contact lens capable of wirelessly monitoring the level of glucose in the tears of diabetic patients. Figure 1 shows the layout of fabricated devices made of glucose sensors, wireless circuit, and display pixel on soft and transparent contact lens substrate (Figure 1a and b). The circuit diagram of the device is illustrated in Figure 1a, with radio frequency antenna receiving signals from a transmitter and a rectifier converting the signals to DC (Figure 1a and c). A continuous network of ultralong Ag nanofibers was used as stretchable electrodes for the antenna and interconnects (Figure 1d). In the case of any change in the concentration of glucose in tear, the sensor resistance changes resulting in the light-emitting diode (LED) pixel turning on or off. The device was tested in vitro using a live rabbit, providing substantial finding for smart contact lenses as one of the promising wearable devices in healthcare system [17].
\n
Figure 1.
(a) (i) Schematic illustration and (ii) operation of the soft, smart contact lens and (iii) the circuit diagram of the smart contact lens system. The soft, smart contact lens is composed of (b) a hybrid substrate; (c) functional devices including rectifier, LED, and glucose sensor; and (d) a transparent, stretchable conductor for antenna and interconnects [17].
\n
\n
\n
3. Sweat analysis
\n
In addition to tear, sweat electrolyte concentrations and blood serum are related [2, 8]. As one of the most readily accessible human biofluids, a great deal of information about the human body and its physical performance could be obtained via monitoring sweat electrolyte concentrations [23, 24]. Several groups have reported the key biomarkers in human sweat (e.g., sodium level, pH change, lactate concentration) relevant to human health and well-being, for monitoring athletic performance during sporting activities [25]. Jia et al. fabricated a skin-worn tattoo-based sensor for real-time monitoring of lactate in human sweat, offering substantial benefits for biomedical as well as sport applications [25]. In another approach, Curto et al. [26] fabricated a wearable and flexible microfluidic platform capable of monitoring changes in the sweat pH in real time. Anastasova et al. [27] developed a flexible microfluidic device for real-time monitoring of metabolite such as lactate as well as electrolytes such as pH and sodium in human sweat. Recently, Gao et al. [28] developed a flexible and wearable device (Figure 2) made of arrays of sensors for real-time monitoring of heavy metals, such as Zn, Cu, and Hg in human sweat. The device fabrication method is presented in Figure 2a, showing the deposition and stripping steps on microelectrodes. The sensing mechanism was based on an electrochemical detection of targeted heavy metals through four microelectrodes, including Au and Bi working electrodes, Ag reference electrode, and an Au counter electrode (Figure 2b and c). The fabricated device demonstrated high stability and selectivity toward heavy metals, providing a great platform to advancing the field of wearable biosensors for healthcare application, via monitoring the level of some heavy metals in human sweat [28]. A balanced level of Zn is necessary in the human body as a low and high Zn concentration can lead to pneumonia and liver damages, respectively [29, 30]. High level of Cu in the human body can lead to several diseases including Wilson’s disease and heart, kidney, and liver failures as well as brain diseases [31, 32]. The fabricated device demonstrated high stability and selectivity toward heavy metals, providing a great platform to advancing the field of wearable biosensors for healthcare application [28].
\n
Figure 2.
(a) A schematic showing the concept of deposition and stripping on microelectrodes. (b) A schematic showing the composition of the microsensor array. (c) Optical image of a flexible sensor array interfacing with a flexible printed circuit connector [28].
\n
\n
\n
4. Saliva analysis
\n
Saliva, as a great diagnostic fluid, can be used in personal health devices for real-time monitoring of chemical markers including salivary lactate analysis [33]. Chai et al. developed a saliva nanosensor with a radio-frequency identification tag, integrated into dental implants for detecting cardiac biomarkers in saliva and predicting close heart attack in patients suffering from cardiovascular diseases [34]. In another approach, an instrumented mouthguard was designed and fabricated by Kim et al. [35] for measuring salivary uric acid levels which could be a biomarker for several diseases including hyperuricemia, gout, physical stress, and renal syndrome. The fabricated device showed high selectivity and sensitivity to low level of uric acid as well as great stability during a 4-h operation period [35]. Mannoor et al. [36] developed a hybrid biosensor made of graphene layers printed onto water-soluble silk, for noninvasive detection of bacteria through body fluids including sweat and saliva. This graphene/silk hybrid device illustrated an extremely high sensitivity to bacteria in body fluid with detection limits down to a single bacterium [36]. In addition, the fabricated device provided the potential users with battery-free operation and wireless communication system via radio frequency [36]. Arakawa et al. [37] designed and fabricated a salivary sensor equipped with a wireless measurement system, embedded onto a mouthguard support, featuring a high sensitivity toward detection of glucose over a range of 5–1000 μmol L−1. The device demonstrated a great stability during a 5-h real-time glucose monitoring period in an artificial saliva with a phantom jaw [37]. In a similar approach, de Castro et al. [38] developed a microfluidic paper-based device integrated into a mouthguard, for continues monitoring of glucose and nitrite in human saliva. The saliva samples were collected from periodontitis and/or diabetes patients as well as healthy individuals. The fabricated device featured a low detection limit of 27 and 7 μmol L−1 for glucose and nitrite, respectively [38].
\n
\n
\n
5. Summary
\n
In summary, there is a great potential for micro- and nanosensors’ integration into healthcare monitoring devices, developing new technologies for noninvasive detection of diseases in the human body. Flexible wearable devices offer promising capabilities in real-time monitoring of body fluids including tear, sweat, and saliva. However, more research is required to expand the use of wearable platforms in continuous analysis of body fluids, providing reliable real-time detection of targeting ions and proteins, among other complex analytes.
\n
\n\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/69186.pdf",chapterXML:"https://mts.intechopen.com/source/xml/69186.xml",downloadPdfUrl:"/chapter/pdf-download/69186",previewPdfUrl:"/chapter/pdf-preview/69186",totalDownloads:792,totalViews:0,totalCrossrefCites:2,totalDimensionsCites:2,totalAltmetricsMentions:0,impactScore:1,impactScorePercentile:59,impactScoreQuartile:3,hasAltmetrics:0,dateSubmitted:"March 21st 2019",dateReviewed:"August 22nd 2019",datePrePublished:null,datePublished:"December 4th 2019",dateFinished:"September 21st 2019",readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/69186",risUrl:"/chapter/ris/69186",book:{id:"7654",slug:"wearable-devices-the-big-wave-of-innovation"},signatures:"Noushin Nasiri",authors:[{id:"234150",title:"Dr.",name:"Noushin",middleName:null,surname:"Nasiri",fullName:"Noushin Nasiri",slug:"noushin-nasiri",email:"noushin.nasiri@mq.edu.au",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/234150/images/system/234150.jpg",institution:{name:"Macquarie University",institutionURL:null,country:{name:"Australia"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Tear analysis",level:"1"},{id:"sec_3",title:"3. Sweat analysis",level:"1"},{id:"sec_4",title:"4. Saliva analysis",level:"1"},{id:"sec_5",title:"5. Summary",level:"1"}],chapterReferences:[{id:"B1",body:'Trung TQ , Lee NE. Flexible and stretchable physical sensor integrated platforms for wearable human-activity monitoring and personal healthcare. Advanced Materials. 2016;28(22):4338-4372\n'},{id:"B2",body:'Nakata S, Arie T, Akita S, Takei K. Wearable, flexible, and multifunctional healthcare device with an ISFET chemical sensor for simultaneous sweat pH and skin temperature monitoring. ACS Sensors. 2017;2(3):443-448\n'},{id:"B3",body:'Tricoli A, Nasiri N, De S. Wearable and miniaturized sensor technologies for personalized and preventive medicine. Advanced Functional Materials. 2017;27(15):1605271\n'},{id:"B4",body:'Arnold JF, Sade RM. Wearable technologies in collegiate sports: The ethics of collecting biometric data from student-athletes. 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Sensors & Actuators, B: Chemical. 2016;227:35-42\n'},{id:"B24",body:'Pribil MM, Laptev GU, Karyakina EE, Karyakin AA. Noninvasive hypoxia monitor based on gene-free engineering of lactate oxidase for analysis of undiluted sweat. Analytical Chemistry. 2014;86(11):5215-5219\n'},{id:"B25",body:'Jia W, Bandodkar AJ, Valdés-Ramírez G, Windmiller JR, Yang Z, Ramírez J, et al. Electrochemical tattoo biosensors for real-time noninvasive lactate monitoring in human perspiration. Analytical Chemistry. 2013;85(14):6553-6560\n'},{id:"B26",body:'Curto VF, Fay C, Coyle S, Byrne R, O’Toole C, Barry C, et al. Real-time sweat pH monitoring based on a wearable chemical barcode micro-fluidic platform incorporating ionic liquids. Sensors & Actuators, B: Chemical. 2012;171-172:1327-1334\n'},{id:"B27",body:'Anastasova S, Crewther B, Bembnowicz P, Curto V, Ip HM, Rosa B, et al. A wearable multisensing patch for continuous sweat monitoring. Biosensors & Bioelectronics. 2017;93:139-145\n'},{id:"B28",body:'Gao W, Nyein HY, Shahpar Z, Fahad HM, Chen K, Emaminejad S, et al. Wearable microsensor array for multiplexed heavy metal monitoring of body fluids. ACS Sensors. 2016;1(7):866-874\n'},{id:"B29",body:'Lassi ZS, Moin A, Bhutta ZA. Zinc supplementation for the prevention of pneumonia in children aged 2 months to 59 months. Cochrane Database of Systematic Reviews. 2016;12:CD005978\n'},{id:"B30",body:'Mohammad MK, Zhou Z, Cave M, Barve A, McClain CJ. Zinc and liver disease. Nutrition in Clinical Practice. 2012;27(1):8-20\n'},{id:"B31",body:'Crisponi G, Nurchi VM, Fanni D, Gerosa C, Nemolato S, Faa G. Copper-related diseases: From chemistry to molecular pathology. Coordination Chemistry Reviews. 2010;254(7-8):876-889\n'},{id:"B32",body:'Huster D. Wilson disease. Best Practice & Research. Clinical Gastroenterology. 2010;24(5):531-539\n'},{id:"B33",body:'Lee J, Garon E, Wong D. Salivary diagnostics. Orthodontics & Craniofacial Research. 2009;12(3):206-211\n'},{id:"B34",body:'Chai PR, Castillo-Mancilla J, Buffkin E, Darling C, Rosen RK, Horvath KJ, et al. Utilizing an ingestible biosensor to assess real-time medication adherence. Journal of Medical Toxicology. 2015;11(4):439-444\n'},{id:"B35",body:'Kim J, Imani S, de Araujo WR, Warchall J, Valdés-Ramírez G, Paixão TRLC, et al. Wearable salivary uric acid mouthguard biosensor with integrated wireless electronics. Biosensors & Bioelectronics. 2015;74:1061-1068\n'},{id:"B36",body:'Mannoor MS, Tao H, Clayton JD, Sengupta A, Kaplan DL, Naik RR, et al. Graphene-based wireless bacteria detection on tooth enamel. Nature Communications. 2012;3:763\n'},{id:"B37",body:'Arakawa T, Kuroki Y, Nitta H, Chouhan P, Toma K, Sawada S-I, et al. Mouthguard biosensor with telemetry system for monitoring of saliva glucose: A novel cavitas sensor. Biosensors and Bioelectronics. 2016;84:106-111\n'},{id:"B38",body:'de Castro LF, de Freitas SV, Duarte LC, de Souza JAC, Paixão TR, Coltro WK. Salivary diagnostics on paper microfluidic devices and their use as wearable sensors for glucose monitoring. Analytical and Bioanalytical Chemistry. 2019:1-10\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Noushin Nasiri",address:"noushin.nasiri@mq.edu.au",affiliation:'
School of Engineering, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, Australia
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1. Introduction
The unfortunate tragedy of thalidomide, in 1962, triggered the emergence and implementation of pharmacovigilance across the globe [1]. Thalidomide was introduced in Germany in 1957 and was widely prescribed for the treatment of morning sickness and nausea in pregnant women. Later it was found that babies were born with shortened or absence of limbs (medically known as phocomelia). In 1962, thalidomide was discontinued from the market due to the increased number of scientific reports describing numerous cases of phocomelia [2]. This tragedy led to the creation of the World Health Organization (WHO) pilot research project for International Drug Monitoring in 1968, with the purpose to develop a system and tools applicable internationally, for detecting previously unknown or poorly understood adverse drug reactions (ADRs) of medicines [3]. Currently, this network has been expanded to more than 140 developed, low- and middle-income countries. These 140 countries participated in the WHO programme for international drug monitoring as member states, and 31 countries have also joined as associate member states. These countries have established pharmacovigilance system at their capacity, to monitor the medication safety. WHO and its collaborating centres are continuously providing technical support for capacity building and strengthening of these pharmacovigilance systems [4].
As per WHO, Pharmacovigilance is defined as a “science of detection, assessment, understanding and prevention of ADRs or any other drug related problems” [5]. This enables the scope of clinical practice of monitoring & reporting of ADRs, analyses the information and sharing the learnings with healthcare providers for prevention of such ADRs, for better patient’s safety and outcomes. Pharmacovigilance and its concepts are evolving as one of the most important components in contemporary clinical and regulatory practice. In clinical trials, most medicines will only be tested for short-term safety and efficacy on a limited number of carefully selected individuals (excluding pregnant women, children and elderly). In some cases, as few as 500, and rarely more than 5000, subjects receive the investigational new drug prior to its release [6]. It is not possible to identify and record many ADRs in such a shorter duration, protected environment and restricted population in trials. After stage three of clinical trial, the medicine is available to be launch in the market and is legally set free for consumption by the general population. Post market experience has shown that many adverse effects, interactions (i.e. with foods or other medicines), and risk factors may come to light even after several years of introducing the medicine into the market [7]. Moreover, many studies have shown that an ADR may result into a significantly decrease in the quality of life, increased hospitalizations, prolonged hospital stay and mortality [8]. Therefore, monitoring the safety of the medicines throughout its life period is pivotal, as most of the ADRs are usually reported during prolonged use.
The pharmacovigilance practice applies equally to medicines used in public health programs, including medicines used in Anti-Tubercular Therapy (ATT). As the management of tuberculosis (TB) involves longer duration of therapy and also multiple drugs, these arise as predisposing factors for the occurrence of ADRs [9]. Such ADRs pose a challenge in the management of TB. Though it is a prolonged treatment, medication must be continued in order to ensure the compliance, otherwise it will end with treatment failure or developing antimicrobial resistance [10]. Generally, patients discontinue the medication due to the emergence of ADRs resulting from the administration of first-line anti-TB drugs. During the course of TB treatment, there may be a risk of morbidity and mortality, particularly with drug-induced hepatitis. Therefore, there are public health program in various countries that systematically monitor, prevent and manage ADRs encountered during the treatment of TB, in order to achieve maximum treatment outcomes [11].
TB is a chronic infection caused primarily by Mycobacterium tuberculosis. The lung is generally the first affected organ, as the infection is usually due to inhalation of infected droplet nuclei. Approximately 80% of the TB cases are pulmonary TB [12]. Around 30% patients who are infected with Human Immune Deficiency Virus (HIV) will also develop active tuberculosis. Factors, such as HIV, Resistant TB, drug–drug interactions raise the complexity of problem. As per the WHO strategy, directly observed treatment short-course (DOTS) therapy for the duration of 6–8 months is one of the important components for the treatment of TB. The short-course therapy is usually performed in 2 phases: the initial phase (2 months) involves the concurrent use of at least 3 drugs to rapidly reduce the bacterial population and prevent emergence of drug-resistant bacteria. The second, continuation phase, (4–6 months) involves fewer drugs and is used to eliminate any remaining bacteria and prevent recurrence. Worldwide, HIV infection has been identified as an important predisposing factor of immune-suppression leading to TB [13]. It increases the susceptibility to primary infection and increases the reactivation rate of TB [14]. Although this regimen is effective in treating active TB, it is associated with many ADRs and poses a significant challenge to completion of treatment. Recommended treatment regimens for TB are given in Table 1.
First line drugs given for Drug Sensitive TB
New patients with pulmonary TB should receive a regimen containing 6 months of rifampicin: (Isoniazid + Rifampicin + Pyrazinamide + Ethambutol) *In populations with known or suspected high levels of isoniazid resistance, new TB patients may receive HRE as therapy in the continuation phase. Recommended: 1. Daily dosage 2. Fixed Dose Combination drugs
Second line drugs given for Rifampicin Resistance/Multi Drug Resistance/Extremely Druf Resistance (RR/MDR/XDR) TB and Multi Drug Resistance (MDR-TB)
Group A: Fluoroquinolones Levofloxacin, Moxifloxacin, Gatifloxacin
Group B: Second-line injectable agents Amikacin, Capreomycin, Kanamycin, (Streptomycin)
Group C: Other core second-line agents Ethionamide/prothionamide, Cycloserine/terizidone, Linezolid, Clofazimine
Group D: Add-on agents (not part of the core MDR-TB regimen), D1 Pyrazinamide Ethambutol,High-dose isoniazid
Multiple types of drug therapy are given for TB, and even new TB patients (sensitive to first-line drugs), are receiving a treatment regimen with a combination of four drugs [15]. There is a chance for developing ADR either for one or the combination of drugs, and that has to be identified for ensuring a sustained treatment compliance, till the completion of ATT. When treatment is given to patients with TB-associated drug resistance, either ionized resistance, multidrug resistance or rifampicin resistance, pre-extensively drug resistance or extensively drug resistance TB, the number of drugs given could be higher, and it becomes imperative to identify the resulting/associated ADRs. In case any ADR takes place, the treatment management has to be done appropriately [16]. For TB patients having HIV co-infection, the treatment given for HIV infection, including the antiretroviral therapy, and/or the medication given for the associated conditions, may overlap with the ADR presented, and so it becomes very important to monitor this group of population for efficient management. In addition, also in TB patients with special medical conditions associated, like associated diabetes mellitus, liver, renal or seizure disorders, and psychosis, the treatment should be done cautiously, by closely observing the progress and monitoring all the ADRs encountered. Furthermore, when new drugs like Bedaquiline (BDQ), Delamanid (DLM) and Pretomanid are initiated at TB programs, it is essential that the associated ADRs are captured promptly for effective management of TB [17].
2.1 ADRs associated with first-line anti-TB drugs
The ATT is expected to cause more ADRs, because it involves combination of several medicines and is used for a longer duration [9]. One of the most common ADRs observed with the administration of ATT is gastrointestinal symptoms, such as nausea, vomiting etc. These ADRs could be symptomatically managed without the need for a change in the dosage of drugs. The hepatotoxicity is also a risk associated with ATT, and its frequency can range from 2–39% in different countries [18]. As compared to Western population, Indian sub-population studies reported high incidence of hepatotoxicity with ATT [19].
2.1.1 Isoniazid
Isoniazid has been shown to be well tolerated at recommended dose. However, systemic or cutaneous hypersensitivity reactions can occasionally occur during the first weeks of treatment [15]. By daily supplementary dose of pyridoxine in vulnerable patients, the risk of peripheral neuropathy can be excluded. In the later stages of treatement, some susceptible patients can develop neurological disturbance, encompassing optic neuritis, toxic psychosis and generalized convulsions. This may require the discontinuation of isoniazid. An uncommon but potentially serious reaction is symptomatic hepatitis, which could be precluded by prompt withdrawal of treatment. Asymptomatic rise in serum concentrations of hepatic transaminases at the beginning of treatment has very low clinical significance. The same resolves spontaneously as the treatment carry on. Other rare adverse effects linked with isoniazid are lupus-like syndrome, pellagra, anemia, and arthralgias [20].
2.1.2 Rifampicin
At currently recommended doses, this drug has been shown to be well tolerated by most of the patients. Occasionally it may cause gastrointestinal reactions including abdominal pain, nausea, vomiting and pruritus with or without rash [21]. With an intermittent drug administration, adverse effects, such as fever, influenza-like syndrome and thrombocytopenia may occur. In HIV-positive TB patients, exfoliative dermatitis is more common. Patients taking the drug 3 times a week, adverse effects including temporary oliguria, dyspnoea and haemolytic anemia have been reported. If the regimen is changed to daily dosage these reactions usually subsided. In the beginning of treatment, moderate rises in serum concentrations of bilirubin and transaminases are common adverse effects are often transient and not clinical significant. A potentially fatal condition is dose-related hepatitis, it is therefore important to not exceed the maximum recommended daily dose of 600 mg.
2.1.3 Pyrazinamide
This drug has been reported to cause various skin reactions, like maculopapular rash, erythema multiforme, exfoliative dermatitis and drug rash with eosinophilia and systemic symptoms (DRESS) syndrome. Among the first-line drugs, pyrazinamide has shown to be the most common drug to cause cutaneous ADRs [22]. Pyrazinamide may cause gastrointestinal intolerance. Hypersensitivity reactions are rare, but have been reported in some patients with modest flushed skin. During the early phases of the treatment, moderate rises in serum transaminase concentrations are common. A rare complication is severe hepatotoxicity. A degree of hyperuricaemia may also occur asymptomatically as a result of inhibition of renal tubular secretion [15]. The treatment may also result into gout, which can be treated with allopurinol. Arthralgia, especially of the shoulders, may occur which can be treated with simple analgesics (especially aspirin). By prescribing regimens with intermittent administration of pyrazinamide, hyperuricaemia and arthralgia may be eliminated. Sideroblastic anemia and photosensitive dermatitis are some of the rare ADRs associated with this drug [7, 8].
2.1.4 Streptomycin
Streptomycin injections are painful, and rash, induration, or sterile abscesses can be formed at injection sites. Numbness and tingling around the mouth occur immediately after injection and cutaneous hypersensitivity reactions can occur. The incidence of ototoxicity associated with the use of ATT may be as high as 25% [23]. With currently recommended doses, the complications like impairment of vestibular function are uncommon. Vertigo is more common than hearing loss. Indications of injury at the 8th cranial (auditory) nerve include ringing in the ears, ataxia, vertigo and deafness. The damage is impermanent and can be reversed by reducing in dosage, or the stopping the treatment with this drug. This damage is commonly occurs within the first 2 months of treatment. More commonly, the other aminoglycoside antibiotics e.g. kanamycin, amikacin and capreomycin are more nephrotoxic than streptomycin. If urinary output falls, albuminuria occurs, or tubular casts are detected in the urine, streptomycin should be stopped, and renal function should be evaluated.
Though WHO’s recommendation is not to use injectable streptomycin, we should take into consideration that other recommended treatments with aminoglycosides may cause similar types of ADRs [17].
2.1.5 Ethambutol
Dose-dependent optic neuritis caused by Ethambutol can result in impairment of visual acuity and color vision in one or both eyes. Early changes are usually reversible, but blindness can occur if treatment is not discontinued promptly. Ocular toxicity is rare when ethambutol is used for 2–3 months at recommended doses. Peripheral neuropathy has been reported in approximately 20% of patients treated with ethambutol. Other rare adverse events include generalized cutaneous reaction, arthralgia and, very rarely, hepatitis [24].
Several studies have reported that the drugs used to treat TB may cause ADRs. Management and prevention of such ADRs are important measures to be adopted to increase tolerance. Generally, with non-serious ADRs, the drugs do not need to be stopped, while with serious ADRs, the drugs often have to be stopped and a modified regimen has to be implemented [9].
2.1.6 Capreomycin
This drug is administered in combination with other first-line drugs. The common ADRs reported are hypersensitivity reactions, including urticaria and rashes, nephrotoxicity, electrolyte disturbance, hearing loss wit tinnitus and vertigo [11].
Grading of toxicity associated with drugs used for TB treatment and the ADRs associated with the anti-TB drugs used for therapy are given in Tables 2 and 3, respectively.
Grade & Level
Toxicity
1 - Mild
Transient or mild discomfort; no limitation in activity; no medical intervention or therapy required.
2 – Moderate
Mild to moderate limitation in activity, some assistance may be needed; none or minimal medical intervention or therapy required.
3 - Severe
Marked limitation in activity, some assistance usually required; medical intervention or therapy required, hospitalization is possible.
4 – Life threatening
Extreme limitation in activity, significant assistance required; significant medical intervention or therapy required, hospitalization or hospice care are probable.
Table 2.
Grades of toxicity resulting from TB treatment [25].
Adverse Drug Reaction
Symptoms and signs
Responsible Drug
Audiovestibular manifestations
Hearing loss, vertigo, new-onset tinnitus
Aminoglycosides, Capreomycin
Blood sugar abnormalities
Dizziness, sweating, fainting, poor response to infections
Most common ADRs associated with the use of anti-TB drugs.
2.2 ADRs associated with second-line anti-TB drugs
Resistant -TB is usually treated with a combination of drugs that are more toxic than isoniazid and rifampicin. These drugs include fluoroquinolones, aminoglycosides, ethionamide, cycloserine, aminosalicyclic acid, linezolid and clofazimine, among others [26]. The main ADRs associated with the use of cycloserine are reported as neurological disorders, including headache, dizziness, vertigo, drowsiness, tremor, convulsions, confusion, psychosis, depression, rashes, allergic dermatitis, megaloblastic anemia, and changes in liver function tests [27]. Minor adverse effects are relatively common, and they can be easily managed with symptomatic treatment. However, some adverse effects can be life-threatening, for example, nephrotoxicity due to aminoglycosides, cardiotoxicity due to fluoroquinolones, gastrointestinal toxicity due to ethionamide or para-amino-salicylic acid, central nervous system toxicity due to cycloserine, etc. [17].
2.3 Multi Drug-resistant TB (MDR-TB)
MDR-TB is caused by organisms that are resistant to isoniazid and rifampicin. As per the WHO reports, an estimated 480 000 worldwide patients developed MDR-TB in 2015, in addition to the 100 000 patients with rifampicin-resistant TB that were newly eligible for MDT-TB treatment [22]. Again, according to WHO, the second highest MDR-TB incident country in the world, China, accounted for 45% of the 580 000 cases, together with Indian and the Russian Federations, with 6.6% of new TB cases and 30% of previously treated cases having MDR/Rifampicin resistant TB.
The novel anti tubercular drugs, namely BDQ and DLM, now included in WHO second-line treatment [28], as well as in some countries, have received conditional approval for use in adults with MDR-TB. BDQ, a new anti TB- drug, has been given approval by the United States Food and Drug Administration in 2012 [29], and by the European Medicines Agency in 2014. In India, BDQ was introduced under the conditional access program in 2015. The safety profile and tolerability of a BDQ-containing treatment regimen used in India has been established. QT prolongation in electrocardiogram reading has been reported as one of the most common ADRs with the use of BDQ; the others include peripheral neuropathy, vomiting, breathlessness and thrombocytopenia [30].
2.4 Prevalence of adverse events associated with second-line anti-TB drugs in children
Children, especially those under 10 years old, can tolerate second-line combination of anti-TB drugs better than adults. In children, the higher rate of ADRs has been observed in those having HIV as comorbid infection, as compared to TB infection alone [14]. Several studies have also revealed that the majority of the adverse events found in children are mild to moderate, thus not requiring interruption or complete cessation of treatment. Moreover, even with the occurrence of few severe adverse events, permanent discontinuation of drugs is rarely necessary [14].
The second–line drugs are generally found to cause more ADRs, as compared to the first-line drugs [31]. The healthcare workers treating children should be aware of this fact and should thus be able to manage such ADRs. Healthcare workers, care givers or parents are required to be trained accordingly, because most of the children may not be able to report the drug-associated ADRs. The MDR-TB treatment outcomes in children are well achieved in many countries by using the currently available drugs [32, 33]. However, the improvement of the MDR-TB treatment programme can be achieved by: (1) implementing targeted or cohort event monitoring of adverse events, with the use of MDR-TB drugs in children; and (2) healthcare works training for a timely ADRs reporting, aiming to achieve the maximum treatment outcomes.
2.5 Causality and severity assessment of anti-TB drugs-associated adverse events
After determining the adverse events (suspected) of anti-TB drugs, the very next step is to establish the causal or temporal relationship between the drug and the event, i.e., is the drug actually causing the event? It is possible that the administered drug and the occurrence of an adverse event may have a close temporal relationship, but still not be a reaction [34].
Having considered the parameters in assessing the temporal relationship, the next step is to address the following question: “Did these medicines actually cause the event?” In other words, “Is the event a reaction?” It is conceivable/acceptable that the administration of a medicine and the occurrence of an event may have a close relationship, but still not be a reaction, for example, death from myocardial infarction. In actual practice, the assessment of the relationship and causality frequently merge, particularly when an event is a well-known reaction and the relationship is close. The two phases occur without conscious deliberation, but should be there nevertheless. However, it is often necessary to gather other knowledge about the medicine, the patient and the event, in order to undertake a deliberate evaluation of these factors, which are actually external to the drug–event association that has occurred. Causality assessment is the methodological approach for evaluating a signal (identification of new safety alert) [35]. As per WHO, the causality assessment scale is the estimated strength of the relationship between the drug and the ADR can be classified as certain, probable, possible, unlikely, conditional/unclassified, unassessable/unclassifiable (Table 4). The Naranjo scale can also be applied for causality assessment, and is algorithm-based (Table 5) [38].
Certain
Event of laboratory test abnormality, with plausible time relationship to drug intake
Cannot be explained by disease or other drugs
Response to withdrawal plausible (pharmacologically, pathologically)
Event definitive pharmacologically or phenomenological (An objective and specific medical disorders or a recognized pharmacological phenomenon)
Rechallenge (if necessary)
Probable
Event or lab test abnormality, with reasonable time relationship during intake
Unlikely to be attributed to disease or other drugs
Response to withdrawal clinically reasonable
Rechallenge not necessary
Possible
Event or laboratory test abnormality, with reasonable time relationship to drug intake
Could also be explained by disease or other drugs
Information on drug withdrawal lacking or unclear
Unlikely
Event or laboratory test abnormality with a time to drug that makes a relationship improbable (but not impossible)
Diseases or other drugs provide plausible explanations
Conditional/unclassified
Event or laboratory test abnormality
More data for proper assessment needed
Or additional data under examination
Unassessable/Unclassifiable
A report suggesting an adverse reaction
Cannot be judged because of insufficient or contradictory information
The total score calculated from this table defines the category as:
a. Definite (>9).
b. Probable (5 to 8).
c. Possible (1 to 4).
d. Unlikely (< 0).
The severity assessment of ADRs can also be categorized in to into seven levels of severity level 1 and 2 are considered less severe or mild, levels 3 and 4 are moderate, and levels 5, 6 and 7 are classified as severe [39]. Severe level of ADRs includes all potentially life threatening ADRs, and the ones causing permanent damage or requiring intensive medical care. Even some other assessment scales classify severe and lethal.
3. Conclusions
The emergence of ADRs continues to remain an important public health issue worldwide, as it is among the ten leading causes of mortality. Early identification and prevention of ADRs during TB treatment will lead to the rational use of medicines and to a reduce burden of antimicrobial resistance. Better adherence within the target population will reassure that monitoring and good communication on risks and benefits provide favorable implications for decisions on medicine procurement. Safety monitoring of medicines is thus a vital and crucial element of any health system. As TB treatment relies on a multi-drug therapy for long duration, the emergence of ADRs is inevitable. Therefore, ADR reporting is essential as it will strengthen the evidence, maximize the benefits and minimize the risks.
Abbreviations
ADRs
Adverse Drug Reactions
ATT
Anti-Tubercular Therapy
BDQ
Bedaquiline
DLM
Delamanid
DOTS
Directly Observed Treatment Short-Course
HIV
Human Immunodeficiency Viruses
MDR-TB
Multid Drug-Resistant Tuberculosis
TB
Tuberculosis
WHO
World Health Organization
DRESS
Drug Rash with Eosinophilia and Systemic Symptoms syndrome
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The occurrence of ADRs associated with the use of ATT is expected, a large number of medicines are combined and used for prolonged duration. The suspected ADRs associated with first line ATT are well documented. However, the drugs used in second line or multidrug resistant to tuberculosis (TB), namely bedaquiline, reported to cause QT prolongation in electrocardiogram reading as one of the most common ADRs. Therefore, early identification and prevention of ADRs during ATT is essential for promoting the rational use and reduce the burden of anti-microbial resistance, besides achieving better treatment outcomes.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/77033",risUrl:"/chapter/ris/77033",signatures:"Vivekanandan Kalaiselvan, Shatrunajay Shukla, Santhanakrishnan Ramesh Kumar, Nikita Mishra, Pawan Kumar and Rajeev Singh Raghuvanshi",book:{id:"9833",type:"book",title:"New Insights into the Future of Pharmacoepidemiology and Drug Safety",subtitle:null,fullTitle:"New Insights into the Future of Pharmacoepidemiology and Drug Safety",slug:"new-insights-into-the-future-of-pharmacoepidemiology-and-drug-safety",publishedDate:"October 13th 2021",bookSignature:"Maria Teresa Herdeiro, Fátima Roque, Adolfo Figueiras and Tânia Magalhães Silva",coverURL:"https://cdn.intechopen.com/books/images_new/9833.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83968-597-2",printIsbn:"978-1-83968-596-5",pdfIsbn:"978-1-83968-598-9",isAvailableForWebshopOrdering:!0,editors:[{id:"227508",title:"Prof.",name:"Maria Teresa",middleName:null,surname:"Herdeiro",slug:"maria-teresa-herdeiro",fullName:"Maria Teresa Herdeiro"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"253107",title:"Dr.",name:"Vivekanandan",middleName:null,surname:"Kalaiselvan",fullName:"Vivekanandan Kalaiselvan",slug:"vivekanandan-kalaiselvan",email:"vivekarts@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"419637",title:"Dr.",name:"Shatrunajay",middleName:null,surname:"Shukla",fullName:"Shatrunajay Shukla",slug:"shatrunajay-shukla",email:"dummy+419637@intechopen.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"419638",title:"Dr.",name:"S.",middleName:null,surname:"Ramesh Kumar",fullName:"S. Ramesh Kumar",slug:"s.-ramesh-kumar",email:"dummy+419638@intechopen.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"419639",title:"Dr.",name:"Nikita",middleName:null,surname:"Mishra",fullName:"Nikita Mishra",slug:"nikita-mishra",email:"dummy+419639@intechopen.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"419640",title:"Dr.",name:"Pawan",middleName:null,surname:"Kumar",fullName:"Pawan Kumar",slug:"pawan-kumar",email:"dummy+419640@intechopen.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"419641",title:"Dr.",name:"Rajeev Singh",middleName:null,surname:"Raghuvanshi",fullName:"Rajeev Singh Raghuvanshi",slug:"rajeev-singh-raghuvanshi",email:"dummy+419641@intechopen.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Importance of ADR reporting in tuberculosis",level:"1"},{id:"sec_2_2",title:"2.1 ADRs associated with first-line anti-TB drugs",level:"2"},{id:"sec_2_3",title:"2.1.1 Isoniazid",level:"3"},{id:"sec_3_3",title:"2.1.2 Rifampicin",level:"3"},{id:"sec_4_3",title:"2.1.3 Pyrazinamide",level:"3"},{id:"sec_5_3",title:"2.1.4 Streptomycin",level:"3"},{id:"sec_6_3",title:"2.1.5 Ethambutol",level:"3"},{id:"sec_7_3",title:"Table 2.",level:"3"},{id:"sec_9_2",title:"2.2 ADRs associated with second-line anti-TB drugs",level:"2"},{id:"sec_10_2",title:"2.3 Multi Drug-resistant TB (MDR-TB)",level:"2"},{id:"sec_11_2",title:"2.4 Prevalence of adverse events associated with second-line anti-TB drugs in children",level:"2"},{id:"sec_12_2",title:"2.5 Causality and severity assessment of anti-TB drugs-associated adverse events",level:"2"},{id:"sec_14",title:"3. Conclusions",level:"1"},{id:"sec_17",title:"Abbreviations",level:"1"}],chapterReferences:[{id:"B1",body:'N. Vargesson, “Thalidomide Embryopathy: An Enigmatic Challenge,” ISRN Developmental Biology, Oct. 31, 2013. https://www.hindawi.com/journals/isrn/2013/241016/ (accessed Feb. 24, 2021).'},{id:"B2",body:'N. Vargesson, “Thalidomide-induced teratogenesis: history and mechanisms,” Birth Defects Res C Embryo Today, vol. 105, no. 2, pp. 140-156, Jun. 2015, doi: 10.1002/bdrc.21096.'},{id:"B3",body:'W. H. Organization, Handbook of resolutions and decisions of the World Health Assembly and the Executive Board. World Health Organization, 1973.'},{id:"B4",body:'D. N. Iessa, “Pharmacovigilance: New Challenges for WHO,” p. 52.'},{id:"B5",body:'“Pharmacovigilance - an overview | ScienceDirect Topics.” https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/pharmacovigilance (accessed Feb. 24, 2021).'},{id:"B6",body:'J. A. Berlin, S. C. Glasser, and S. S. 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Available: https://www.who.int/docs/default-source/documents/tuberculosis/a-practical-handbook-on-the-pharmacovigilance-of-medicines-used-in-the-treatment-of-tuberculosis.pdf?sfvrsn=6e5fc0cf_5.'},{id:"B10",body:'F. Imam et al., “Adverse drug reaction prevalence and mechanisms of action of first-line anti-tubercular drugs,” Saudi Pharmaceutical Journal, vol. 28, no. 3, pp. 316-324, Mar. 2020, doi: 10.1016/j.jsps.2020.01.011.'},{id:"B11",body:'“Pivotal role of Pharmacovigilance Programme of India in containment of antimicrobial resistance in India Agrawal V, Shrivastava TP, Adusumilli PK, Vivekanandan K, Thota P, Bhushan S - Perspect Clin Res.” https://www.picronline.org/article.asp?issn=2229-3485;year=2019;volume=10;issue=3;spage=140;epage=144;aulast=Agrawal (accessed Mar. 17, 2021).'},{id:"B12",body:'C. Hoffmann, “Pulmonary tuberculosis in adults,” in Tuberculosis, Elsevier, 2009, pp. 332-341.'},{id:"B13",body:'T. T. Todorova, G. Tsankova, and N. L. and T. Kostadinova, “Tuberculosis and HIV — Doubling the Fatality,” Immunopathology and Immunomodulation, Nov. 2015, doi: 10.5772/61138.'},{id:"B14",body:'J. Bruchfeld, M. Correia-Neves, and G. Källenius, “Tuberculosis and HIV Coinfection,” Cold Spring Harb Perspect Med, vol. 5, no. 7, Jul. 2015, doi: 10.1101/cshperspect.a017871.'},{id:"B15",body:'World Health Organization and Stop TB Initiative (World Health Organization), Eds., Treatment of tuberculosis: guidelines, 4th ed. Geneva: World Health Organization, 2010.'},{id:"B16",body:'“WHO_HTM_TB_2014.23_eng.pdf.” Accessed: Mar. 17, 2021. [Online]. Available: https://apps.who.int/iris/bitstream/handle/10665/137334/WHO_HTM_TB_2014.23_eng.pdf;jsessionid=3F28C9E7FB3CC604788D92E5CEB971F8?sequence=1.'},{id:"B17",body:'World Health Organization, WHO consolidated guidelines on drug-resistant tuberculosis treatment. 2019.'},{id:"B18",body:'“Risk Factors of Hepatotoxicity During Anti-tuberculosis Treatment.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923276/ (accessed Feb. 24, 2021).'},{id:"B19",body:'P. R et al., “Hepatic toxicity in South Indian patients during treatment of tuberculosis with short-course regimens containing isoniazid, rifampicin and pyrazinamide,” Tubercle, Jun. 1986. https://pubmed.ncbi.nlm.nih.gov/3775870/ (accessed Feb. 24, 2021).'},{id:"B20",body:'“WHO | Toman’s tuberculosis: case detection, treatment and monitoring: questions and answers (2nd edition),” WHO. https://www.who.int/tb/publications/toman/en/ (accessed Feb. 24, 2021).'},{id:"B21",body:'“Treatment of Tuberculosis American Thoracic Society, CDC, and Infectious Diseases Society of America.” https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5211a1.htm (accessed Feb. 24, 2021).'},{id:"B22",body:'“Prevalence of adverse drug reaction with first-line drugs among patients treated for pulmonary tuberculosis - Clinical Epidemiology and Global Health.” https://cegh.net/article/S2213-3984(15)00073−1/fulltext (accessed Feb. 24, 2021).'},{id:"B23",body:'M. Rd, S. Cr, and L. Ps, “Risk factors for the development of auditory toxicity in patients receiving aminoglycosides,” The Journal of infectious diseases, Jan. 1984. https://pubmed.ncbi.nlm.nih.gov/6693788/ (accessed Feb. 24, 2021).'},{id:"B24",body:'X. Lv et al., “Adverse Reactions Due to Directly Observed Treatment Strategy Therapy in Chinese Tuberculosis Patients: A Prospective Study,” PLOS ONE, vol. 8, no. 6, p. e65037, Jun. 2013, doi: 10.1371/journal.pone.0065037.'},{id:"B25",body:'C. Sekaggya-Wiltshire et al., “Anti-TB drug concentrations and drug-associated toxicities among TB/HIV-coinfected patients,” J Antimicrob Chemother, vol. 72, no. 4, pp. 1172-1177, Apr. 2017, doi: 10.1093/jac/dkw534.'},{id:"B26",body:'K. E. Dooley et al., “Old Drugs, New Purpose: Retooling Existing Drugs for Optimized Treatment of Resistant Tuberculosis,” Clinical Infectious Diseases, vol. 55, no. 4, pp. 572-581, Aug. 2012, doi: 10.1093/cid/cis487.'},{id:"B27",body:'“National Formulary of India 5th Edition, 2016, Page 208.” Indian Pharmacopoeia Commission.'},{id:"B28",body:'M. Grzemska, “Updated WHO MDR-TB treatment guidelines and the use of new drugs in children,” Resid Pediatr, vol. 7, no. Supl, pp. 7-10, Oct. 2017, doi: 10.25060/residpediatr-2017.v7s1-03.'},{id:"B29",body:'S. Yadav, G. Rawal, and M. Baxi, “Bedaquiline: A Novel Antitubercular Agent for the Treatment of Multidrug-Resistant Tuberculosis,” J Clin Diagn Res, vol. 10, no. 8, pp. FM01–FM02, Aug. 2016, doi: 10.7860/JCDR/2016/19052.8286.'},{id:"B30",body:'“Effectiveness and safety of bedaquiline under conditional access program for treatment of drug-resistant tuberculosis in India: An interim analysis - PubMed.” https://pubmed.ncbi.nlm.nih.gov/32192613/ (accessed Feb. 24, 2021).'},{id:"B31",body:'“First– and Second–Line Drugs and Drug Resistance | IntechOpen.” https://www.intechopen.com/books/tuberculosis-current-issues-in-diagnosis-and-management/first-and-second-line-drugs-and-drug-resistance (accessed Feb. 24, 2021).'},{id:"B32",body:'H. H. Tola, K. J. Khadoura, W. Jimma, S. Nedjat, and R. Majdzadeh, “Multidrug resistant tuberculosis treatment outcome in children in developing and developed countries: A systematic review and meta-analysis,” International Journal of Infectious Diseases, vol. 96, pp. 12-18, Jul. 2020, doi: 10.1016/j.ijid.2020.03.064.'},{id:"B33",body:'H. S. Schaaf, S. Thee, L. van der Laan, A. C. Hesseling, and A. J. Garcia-Prats, “Adverse effects of oral second-line antituberculosis drugs in children,” Expert Opin Drug Saf, vol. 15, no. 10, pp. 1369-1381, Oct. 2016, doi: 10.1080/14740338.2016.1216544.'},{id:"B34",body:'H. S. Rehan, D. Chopra, and A. K. Kakkar, “Physician’s guide to pharmacovigilance: Terminology and causality assessment,” European Journal of Internal Medicine, vol. 20, no. 1, pp. 3-8, Jan. 2009, doi: 10.1016/j.ejim.2008.04.019.'},{id:"B35",body:'“UMC | What is a signal?” https://www.who-umc.org/research-scientific-development/signal-detection/what-is-a-signal/ (accessed Mar. 17, 2021).'},{id:"B36",body:'S. A. Zaki, “Adverse drug reaction and causality assessment scales,” Lung India, vol. 28, no. 2, pp. 152-153, 2011, doi: 10.4103/0970-2113.80343.'},{id:"B37",body:'“ADVERSE DRUG REACTION-CAUSALITY ASSESSMENT.” Accessed: Mar. 17, 2021. [Online]. Available: http://www.ijrpc.com/files/00050.pdf.'},{id:"B38",body:'R. P. Naidu, “Causality assessment: A brief insight into practices in pharmaceutical industry,” Perspect Clin Res, vol. 4, no. 4, pp. 233-236, 2013, doi: 10.4103/2229-3485.120173.'},{id:"B39",body:'S. C. Hartwig, J. Siegel, and P. J. Schneider, “Preventability and severity assessment in reporting adverse drug reactions,” Am J Hosp Pharm, vol. 49, no. 9, pp. 2229-2232, Sep. 1992.'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Vivekanandan Kalaiselvan",address:"vivekarts@gmail.com;, kalaiselvan.ipc@gov.in",affiliation:'
Indian Pharmacopoeia Commission, Ministry of Health and Family Welfare, Government of India, India
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Definition of Terms:
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Book - collection of Works distributed in a book format, whose selection, coordination, preparation, and arrangement has been performed and published by IntechOpen, and in which the Work is included in its entirety in an unmodified form along with one or more other contributions, each constituting separate and independent sections, but together assembled into a collective whole.
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Work - a book Chapter (as well as Conference Papers), including any and all content, graphics, images and/or other materials forming part of, or accompanying, the Chapter/Conference Paper.
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Attribution – appropriate credit for the used Work or book.
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Rules of Attribution for Works Published by IntechOpen
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With the purpose of protecting Authors' copyright and the transparent reuse of OA (Open Access) content, IntechOpen has developed Rules of Attribution of Works licensed under Creative Commons licenses.
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All Chapters published in IntechOpen books prior to October 2011 are licensed under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported license (CC BY-NC-SA 3.0);
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All Chapters published in IntechOpen books after October 2011 are licensed under the Creative Commons Attribution 3.0 Unported license (CC BY 3.0);
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In case you reuse or republish any of the Works licensed under CC licenses, you must abide by the guidelines outlined below:
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1. Rules for reusing of books in their entirety or significant parts of books
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All rights to Books and other compilations published on the IntechOpen platform and in print are reserved by IntechOpen. The Copyright to Books and other compilations is subject to a separate Copyright from any that exists in the included Works.
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A Book in its entirety or a significant part of a Book cannot be translated freely without specific written consent by the publisher. Further information can be obtained at permissions@intechopen.com.
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In instances where permission is obtained from the publisher for reusing or republishing the Book, or significant parts of the Book, all of the following conditions apply:
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Information about the first publisher must be provided – please note the fact that the material was originally published by IntechOpen as an OA (Open Access) publication must be acknowledged;
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All original Academic Editor(s) must be credited;
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Since you are reusing content that someone else created and allowed you to use freely, you must credit all Authors involved;
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The type of license that is available for the Works must be indicated, as well as a link to the license provided, so that others can investigate the terms of the license. You will be aware that the material can be used for free in consequence of the CC license attribution, so you must acknowledge that fact. It is not sufficient that the material is Creative Commons, because that says nothing about how the material can actually be used. There are different CC licenses and you have to identify the specific license that is being used;
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Any original Copyright Notices associated, with the Works which constitute the Book must be kept intact;
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Provision of the original title of the Book, as well as the original titles of any individual Works;
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Provision of the URL where the Book is hosted, with a notice to the effect that the Book is an OA (Open Access) publication;
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Provision of the URL to every individual Work which constitutes the Book with a notice that the Work is an OA (Open Access) publication. As the material has been accessed for free, it is incumbent upon you to provide the source so that others can also access it for free.
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Every single Work that is used has to be attributed in the way described. If you are unsure about proper attribution, please write to permissions@intechopen.com.
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Individual Works originally published in IntechOpen books are licensed under Creative Commons licenses and can be freely used under terms of the respective CC license, if properly attributed. In order to properly attribute the Work you must respect all the conditions outlined below:
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Credit all Authors – since you are reusing contents that someone created and allowed you to use freely, you have to acknowledge authorship;
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Indicate the type of license under which the Work is available and provide the URL to the license so others can find out the license terms. Preferably keep intact any original Copyright Notice associated with the Chapter (if any). You will be aware that the material can be used for free in consequence of the CC license attribution, so you must acknowledge that fact. It is not sufficient that the material is Creative Commons, because that says nothing about how the material can actually be used. There are different CC licenses and you have to identify the specific license that is being used;
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Provide the URL where the Work is hosted, preferably providing the original title of the Work, as well as the original title of the Book with a notification that the Work is an OA (Open Access) publication. As the material has been accessed for free, it is incumbent upon you to provide the source so that others can also access it for free;
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Provide information about the first publisher – please note the fact that the material was originally published by IntechOpen as an OA (Open Access) Work must be acknowledged.
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Every single Work that is used has to be attributed in the way as described. If you are unsure about proper attribution, please contact Us at permissions@intechopen.com.
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In the event that you use more than one of IntechOpen's Works published in one or more books (but not a significant part of the book that is under separate Copyright), each of these have to be properly attributed in the way described.
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IntechOpen does not have any claims on newly created copyrighted Works, but the Works originally published by IntechOpen must be properly attributed.
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All these rules apply to BOTH online and offline use.
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Parts of the Rules of Attribution are based on Work Attributing Creative Commons Materials published by the Australian Research Council Centre of Excellence for Creative Industries and Innovation, in partnership with Creative Commons Australia, which can be found at creativecommons.org.au licensed under Creative Commons Attribution 2.5 Australia license, and Best practices for attribution published by Creative Commons, which can be found at wiki.creativecommons.org under the Creative Commons Attribution 4.0 license.
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All the above rules are subject to change, IntechOpen reserves the right to take appropriate action if any of the conditions outlined above are not met.
Work - a book Chapter (as well as Conference Papers), including any and all content, graphics, images and/or other materials forming part of, or accompanying, the Chapter/Conference Paper.
\n\n
Attribution – appropriate credit for the used Work or book.
\n\n
Creative Commons licenses – enable licensors to retain copyright while allowing others to use their Works in an appropriate way.
\n\n
Rules of Attribution for Works Published by IntechOpen
\n\n
With the purpose of protecting Authors' copyright and the transparent reuse of OA (Open Access) content, IntechOpen has developed Rules of Attribution of Works licensed under Creative Commons licenses.
\n\n
\n\t
All Chapters published in IntechOpen books prior to October 2011 are licensed under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported license (CC BY-NC-SA 3.0);
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All Chapters published in IntechOpen books after October 2011 are licensed under the Creative Commons Attribution 3.0 Unported license (CC BY 3.0);
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\n\n
In case you reuse or republish any of the Works licensed under CC licenses, you must abide by the guidelines outlined below:
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1. Rules for reusing of books in their entirety or significant parts of books
\n\n
All rights to Books and other compilations published on the IntechOpen platform and in print are reserved by IntechOpen. The Copyright to Books and other compilations is subject to a separate Copyright from any that exists in the included Works.
\n\n
A Book in its entirety or a significant part of a Book cannot be translated freely without specific written consent by the publisher. Further information can be obtained at permissions@intechopen.com.
\n\n
In instances where permission is obtained from the publisher for reusing or republishing the Book, or significant parts of the Book, all of the following conditions apply:
\n\n
\n\t
Information about the first publisher must be provided – please note the fact that the material was originally published by IntechOpen as an OA (Open Access) publication must be acknowledged;
\n\t
All original Academic Editor(s) must be credited;
\n\t
Since you are reusing content that someone else created and allowed you to use freely, you must credit all Authors involved;
\n\t
The type of license that is available for the Works must be indicated, as well as a link to the license provided, so that others can investigate the terms of the license. You will be aware that the material can be used for free in consequence of the CC license attribution, so you must acknowledge that fact. It is not sufficient that the material is Creative Commons, because that says nothing about how the material can actually be used. There are different CC licenses and you have to identify the specific license that is being used;
\n\t
Any original Copyright Notices associated, with the Works which constitute the Book must be kept intact;
\n\t
Provision of the original title of the Book, as well as the original titles of any individual Works;
\n\t
Provision of the URL where the Book is hosted, with a notice to the effect that the Book is an OA (Open Access) publication;
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Provision of the URL to every individual Work which constitutes the Book with a notice that the Work is an OA (Open Access) publication. As the material has been accessed for free, it is incumbent upon you to provide the source so that others can also access it for free.
\n
\n\n
Every single Work that is used has to be attributed in the way described. If you are unsure about proper attribution, please write to permissions@intechopen.com.
\n\n
2. Rules of attribution for works published by IntechOpen
\n\n
Individual Works originally published in IntechOpen books are licensed under Creative Commons licenses and can be freely used under terms of the respective CC license, if properly attributed. In order to properly attribute the Work you must respect all the conditions outlined below:
\n\n
\n\t
Credit all Authors – since you are reusing contents that someone created and allowed you to use freely, you have to acknowledge authorship;
\n\t
Indicate the type of license under which the Work is available and provide the URL to the license so others can find out the license terms. Preferably keep intact any original Copyright Notice associated with the Chapter (if any). You will be aware that the material can be used for free in consequence of the CC license attribution, so you must acknowledge that fact. It is not sufficient that the material is Creative Commons, because that says nothing about how the material can actually be used. There are different CC licenses and you have to identify the specific license that is being used;
\n\t
Provide the URL where the Work is hosted, preferably providing the original title of the Work, as well as the original title of the Book with a notification that the Work is an OA (Open Access) publication. As the material has been accessed for free, it is incumbent upon you to provide the source so that others can also access it for free;
\n\t
Provide information about the first publisher – please note the fact that the material was originally published by IntechOpen as an OA (Open Access) Work must be acknowledged.
\n
\n\n
Every single Work that is used has to be attributed in the way as described. If you are unsure about proper attribution, please contact Us at permissions@intechopen.com.
\n\n
In the event that you use more than one of IntechOpen's Works published in one or more books (but not a significant part of the book that is under separate Copyright), each of these have to be properly attributed in the way described.
\n\n
IntechOpen does not have any claims on newly created copyrighted Works, but the Works originally published by IntechOpen must be properly attributed.
\n\n
All these rules apply to BOTH online and offline use.
\n\n
Parts of the Rules of Attribution are based on Work Attributing Creative Commons Materials published by the Australian Research Council Centre of Excellence for Creative Industries and Innovation, in partnership with Creative Commons Australia, which can be found at creativecommons.org.au licensed under Creative Commons Attribution 2.5 Australia license, and Best practices for attribution published by Creative Commons, which can be found at wiki.creativecommons.org under the Creative Commons Attribution 4.0 license.
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All the above rules are subject to change, IntechOpen reserves the right to take appropriate action if any of the conditions outlined above are not met.
\n\n
Policy last updated: 2016-06-09
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Shohel"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"954",title:"Thermodynamics",slug:"thermodynamics",parent:{id:"158",title:"Metals and Nonmetals",slug:"metals-and-nonmetals"},numberOfBooks:2,numberOfSeries:0,numberOfAuthorsAndEditors:61,numberOfWosCitations:7,numberOfCrossrefCitations:10,numberOfDimensionsCitations:15,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicId:"954",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"8416",title:"Non-Equilibrium Particle Dynamics",subtitle:null,isOpenForSubmission:!1,hash:"2c3add7639dcd1cb442cb4313ea64e3a",slug:"non-equilibrium-particle-dynamics",bookSignature:"Albert S. Kim",coverURL:"https://cdn.intechopen.com/books/images_new/8416.jpg",editedByType:"Edited by",editors:[{id:"21045",title:"Prof.",name:"Albert S.",middleName:null,surname:"Kim",slug:"albert-s.-kim",fullName:"Albert S. Kim"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7661",title:"Heat and Mass Transfer",subtitle:"Advances in Science and Technology Applications",isOpenForSubmission:!1,hash:"c29b5c2ce24925a935ca52b8344fbb99",slug:"heat-and-mass-transfer-advances-in-science-and-technology-applications",bookSignature:"Alfredo Iranzo",coverURL:"https://cdn.intechopen.com/books/images_new/7661.jpg",editedByType:"Edited by",editors:[{id:"67352",title:"Dr.",name:"Alfredo",middleName:null,surname:"Iranzo",slug:"alfredo-iranzo",fullName:"Alfredo Iranzo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:2,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"67726",doi:"10.5772/intechopen.86322",title:"CFD Simulation of Heat and Mass Transfer for Climate Control in Greenhouses",slug:"cfd-simulation-of-heat-and-mass-transfer-for-climate-control-in-greenhouses",totalDownloads:1120,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"Greenhouse plant production involves a number of processes such as transpiration, condensation, photosynthesis, and climate control. Such processes, in turn, set off mass and heat transfer phenomena that influence not only the quality and quantity of crop production but also its environmental cost. While these processes have considerably been analyzed in separate, they strongly interact with one another. For instance, increased radiation (mainly thermal infrared) increases temperature, reduces humidity, consequently increases transpiration, and affects CO2 exchange as well as other reaction rates. Computational fluid dynamics (CFD) is a numerical tool with a solid physical basis which allows, through the construction of a computational model, to simulate the fluid flow environment. Heating, ventilation, and condensation have been analyzed in the greenhouse environment with CFD techniques. The current challenge is the interaction of these processes and their impact on the production system. The present work summarizes some CFD investigations carried out in this topic, in order to analyze the processes of heat and mass transfer in a greenhouse for agronomic purposes.",book:{id:"7661",slug:"heat-and-mass-transfer-advances-in-science-and-technology-applications",title:"Heat and Mass Transfer",fullTitle:"Heat and Mass Transfer - Advances in Science and Technology Applications"},signatures:"Cruz Ernesto Aguilar Rodriguez and Jorge Flores Velazquez",authors:[{id:"173578",title:"Dr.",name:"Jorge",middleName:null,surname:"Flores-Velazquez",slug:"jorge-flores-velazquez",fullName:"Jorge Flores-Velazquez"}]},{id:"66158",doi:"10.5772/intechopen.84706",title:"Numerical Solution to Two-Dimensional Freezing and Subsequent Defrosting of Logs",slug:"numerical-solution-to-two-dimensional-freezing-and-subsequent-defrosting-of-logs",totalDownloads:620,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"Two-dimensional mutually connected mathematical models have been created, solved, and verified for the transient non-linear heat conduction in logs during their freezing and subsequent defrosting. The models reflect the influence of the internal sources of latent heat of both the free and bound water on the logs’ freezing process and also the impact of the temperature on the fiber saturation point of wood species, with whose participation the current values of the thermo-physical characteristics in each separate volume point of the subjected to freezing and subsequent defrosting logs are computed. The chapter presents solutions of the models with explicit form of the finite-difference method and their validation towards own experimental studies. Results from experimental and simulative investigation of 2D non-stationary temperature distribution in the longitudinal section of beech and pine logs with a diameter of 0.24 m and length of 0.48 m during their many hours freezing in a freezer and subsequent defrosting at room temperature are presented, visualized, and analyzed.",book:{id:"7661",slug:"heat-and-mass-transfer-advances-in-science-and-technology-applications",title:"Heat and Mass Transfer",fullTitle:"Heat and Mass Transfer - Advances in Science and Technology Applications"},signatures:"Nencho Deliiski and Natalia Tumbarkova",authors:[{id:"43040",title:"Prof.",name:"Nencho",middleName:"Stanev",surname:"Deliiski",slug:"nencho-deliiski",fullName:"Nencho Deliiski"},{id:"284649",title:"Dr.",name:"Natalia",middleName:"Yordanova",surname:"Tumbarkova",slug:"natalia-tumbarkova",fullName:"Natalia Tumbarkova"}]},{id:"67626",doi:"10.5772/intechopen.86738",title:"The Boundary Element Method for Fluctuating Active Colloids",slug:"the-boundary-element-method-for-fluctuating-active-colloids",totalDownloads:920,totalCrossrefCites:0,totalDimensionsCites:2,abstract:"The boundary element method (BEM) is a computational method particularly suited to solution of linear partial differential equations (PDEs), including the Laplace and Stokes equations, in complex geometries. The PDEs are formulated as boundary integral equations over bounding surfaces, which can be discretized for numerical solution. This manuscript reviews application of the BEM for simulation of the dynamics of “active” colloids that can self-propel through liquid solution. We introduce basic concepts and model equations for both catalytically active colloids and the “squirmer” model of a ciliated biological microswimmer. We review the foundations of the BEM for both the Laplace and Stokes equations, including the application to confined geometries, and the extension of the method to include thermal fluctuations of the colloid. Finally, we discuss recent and potential applications to research problems concerning active colloids. The aim of this review is to facilitate development and adoption of boundary element models that capture the interplay of deterministic and stochastic effects in the dynamics of active colloids.",book:{id:"8416",slug:"non-equilibrium-particle-dynamics",title:"Non-Equilibrium Particle Dynamics",fullTitle:"Non-Equilibrium Particle Dynamics"},signatures:"William E. Uspal",authors:[{id:"279308",title:"Prof.",name:"William",middleName:null,surname:"Uspal",slug:"william-uspal",fullName:"William Uspal"}]},{id:"66487",doi:"10.5772/intechopen.85735",title:"Mean Aspects Controlling Supercritical CO2 Precipitation Processes",slug:"mean-aspects-controlling-supercritical-co-sub-2-sub-precipitation-processes",totalDownloads:736,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"The use of supercritical CO2 is an excellent alternative in extraction, particle precipitation, impregnation and reaction processes due to its special properties. Solubility of the compound in supercritical CO2 drives the precipitation process in different ways. In supercritical antisolvent process, mass and heat transfers, phase equilibria, nucleation, and growth of the compound to be precipitated are the main phenomena that should be taken into account. Mass transfer conditions the morphology and particle size of the final product. This transfer could be tuned altering operating conditions. Heat transfer in non-isothermal process influences on mixing step the size of generated microparticles. In rapid expansion of supercritical solution, phenomena as the phase change from supercritical to a CO2 gas flow, rapid mass transfer and crystallization of the compound, and expansion jet define the morphology and size of the final product. These phenomena a priori could be modulated tuning a large number of operating parameters through the experiments, but the correlations and modeling of these processes are necessary to clarify the relative importance of each one. Moreover, particle agglomeration in the expansion jet and CO2 condensation are determinant phenomena which should be avoided in order to conserve fine particles in the final product.",book:{id:"7661",slug:"heat-and-mass-transfer-advances-in-science-and-technology-applications",title:"Heat and Mass Transfer",fullTitle:"Heat and Mass Transfer - Advances in Science and Technology Applications"},signatures:"Antonio Montes, Clara Pereyra and Enrique J. Martínez de la Ossa",authors:[{id:"55991",title:"Mr.",name:"Antonio",middleName:null,surname:"Montes",slug:"antonio-montes",fullName:"Antonio Montes"},{id:"55992",title:"Dr.",name:"Clara",middleName:null,surname:"Pereyra",slug:"clara-pereyra",fullName:"Clara Pereyra"},{id:"55993",title:"Dr.",name:"Enrique",middleName:null,surname:"Martinez De La Ossa",slug:"enrique-martinez-de-la-ossa",fullName:"Enrique Martinez De La Ossa"}]},{id:"66317",doi:"10.5772/intechopen.85254",title:"Review Heat Transfer of Non-Newtonian Fluids in Agitated Tanks",slug:"review-heat-transfer-of-non-newtonian-fluids-in-agitated-tanks",totalDownloads:1001,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"The heating and cooling of non-Newtonian liquids in tanks with mechanical impellers are operations commonly employed as chemical reactors, heat exchangers, distillers, extractors, thinners and decanters. In particular, the design of heat exchangers (jackets, helical coils, spiral coils and vertical tubular baffles) in tanks requires the prior knowledge of the rheology of the liquid for the calculation of the convection coefficients and the Reynolds number, in order to obtain the area thermal exchange. This chapter aimed to present the basic concepts of tanks with agitation, non-Newtonian liquids, hydrodynamics, heat transfer and, finally, with a practical design example for engineers and undergraduate students.",book:{id:"7661",slug:"heat-and-mass-transfer-advances-in-science-and-technology-applications",title:"Heat and Mass Transfer",fullTitle:"Heat and Mass Transfer - Advances in Science and Technology Applications"},signatures:"Vitor da Silva Rosa and Deovaldo de Moraes Júnior",authors:[{id:"187128",title:"Ph.D.",name:"Vitor",middleName:null,surname:"Rosa",slug:"vitor-rosa",fullName:"Vitor Rosa"},{id:"188792",title:"Dr.",name:"Deovaldo",middleName:null,surname:"Moraes Júnior",slug:"deovaldo-moraes-junior",fullName:"Deovaldo Moraes Júnior"}]}],mostDownloadedChaptersLast30Days:[{id:"66878",title:"Design of Industrial Falling Film Evaporators",slug:"design-of-industrial-falling-film-evaporators",totalDownloads:1753,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The high performance evaporators are important for process industries such as food, desalination and refineries. The falling film evaporators have many advantages over flooded and vertical tubes that make them best candidate for processes industries application. The heat transfer area is the key parameter in designing of an evaporator and many correlations are available to estimate the size of tube bundle. Unfortunately, most of the correlation is available only for pure water and above 322 K saturation temperatures. Out of these conditions, the areas are designed by the extrapolation of existing correlations. We demonstrated that the actual heat transfer values are 2–3-fold higher at lower temperature and hence simple extrapolated estimation leads to inefficient and high capital cost design. We proposed an accurate heat transfer correlation for falling film evaporators that can capture both, low temperature evaporation and salt concentration effectively. It is also embedded with unique bubble-assisted evaporation parameter that can be only observed at low temperature and it enhances the heat transfer. The proposed correlation is applicable from 280 to 305 K saturation temperatures and feed water concentration ranges from 35,000 to 95,000 ppm. The uncertainty of measured data is less than 5% and RMS of regressed data is 3.5%. In this chapter, first part summarized the all available correlations and their limitations. In second part, falling film evaporation heat transfer coefficient (FFHTC) is proposed and model is developed. In the last part, experimentation is conducted and FFHTC developed and compared with conventional correlations.",book:{id:"7661",slug:"heat-and-mass-transfer-advances-in-science-and-technology-applications",title:"Heat and Mass Transfer",fullTitle:"Heat and Mass Transfer - Advances in Science and Technology Applications"},signatures:"Muhammad Wakil Shahzad, Muhammad Burhan and Kim Choon Ng",authors:[{id:"174208",title:"Dr.",name:"Muhammad Wakil",middleName:null,surname:"Shahzad",slug:"muhammad-wakil-shahzad",fullName:"Muhammad Wakil Shahzad"},{id:"249811",title:"Dr.",name:"Muhammad",middleName:null,surname:"Burhan",slug:"muhammad-burhan",fullName:"Muhammad Burhan"},{id:"254696",title:"Prof.",name:"Kim Choon",middleName:null,surname:"Ng",slug:"kim-choon-ng",fullName:"Kim Choon Ng"}]},{id:"66102",title:"Heat and Mass Transfer of Additive Manufacturing Processes for Metals",slug:"heat-and-mass-transfer-of-additive-manufacturing-processes-for-metals",totalDownloads:1302,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Additive manufacturing (AM), a method in which a part is fabricated layer by layer from a digital design package, provides the potential to produce complex components at reduced cost and time. Many techniques (using many different names) have been developed to accomplish this via melting or solid-state joining. However, to date, only a handful can be used to produce metallic parts that fulfill the requirements of industrial applications. The thermal physics and weld pool behaviors in metal AM process have decisive influence on the deposition quality, the microstructure and service performance of the depositions. Accurate analysis and calculation of thermal processes and weld pool behaviors are of great significance to the metallurgy analysis, stress and deformation analysis, process control and process optimization etc. Numerical modeling is also a necessary way to turn welding from qualitative description and experience-based art into quantitative analysis- and science-based engineering branch. In this chapter, two techniques for producing metal parts are explored, with a focus on the thermal science of metal AM: fluid flow and heat transfer. Selective laser melting (SLM) is the one that is most widely used because it typically has the best resolution. Another is named metal fused-coated additive manufacturing (MFCAM) that is cost competitive and efficient in producing large and middle-complex components in aerospace applications.",book:{id:"7661",slug:"heat-and-mass-transfer-advances-in-science-and-technology-applications",title:"Heat and Mass Transfer",fullTitle:"Heat and Mass Transfer - Advances in Science and Technology Applications"},signatures:"Zhengying Wei and Jun Du",authors:[{id:"47614",title:"Prof.",name:"Zhengying",middleName:null,surname:"Wei",slug:"zhengying-wei",fullName:"Zhengying Wei"},{id:"282052",title:"Dr.",name:"Jun",middleName:null,surname:"Du",slug:"jun-du",fullName:"Jun Du"}]},{id:"66563",title:"Heat and Mass Transfer in Outward Convex Corrugated Tube Heat Exchangers",slug:"heat-and-mass-transfer-in-outward-convex-corrugated-tube-heat-exchangers",totalDownloads:1037,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Heat and mass transfer in outward convex corrugated tube heat exchangers is of significant importance for the optimization, fabrication, and application of outward convex corrugated tube heat exchangers. This chapter gives a deep investigation of the heat and mass transfer in outward convex corrugated tube heat exchangers. Based on the experimental setup developed, the performances of a novel outward convex corrugated tube heat exchanger are presented. Simulation methods are then used to detail the heat and mass transfer at tube side and shell side of the outward convex corrugated tube heat exchanger, and these include the flow structure, temperature distribution, and turbulence kinetic energy. Heat and mass transfer enhancements of the outward convex corrugated tube heat exchanger are also studied, and they are from tube side, shell side, and overall system aspects. Finally, multi-objective optimization of the outward convex corrugated tube heat exchanger is conducted to obtain the optimal performances through using Response Surface Methodology (RSM) and Non-dominated Sorting Genetic Algorithm (NSGA-II). Main conclusions and future outlook are then briefly stated and summarized. We firmly believe that the contents presented in this chapter can not only enrich the knowledge of heat exchangers but also develop methods for studying heat exchangers.",book:{id:"7661",slug:"heat-and-mass-transfer-advances-in-science-and-technology-applications",title:"Heat and Mass Transfer",fullTitle:"Heat and Mass Transfer - Advances in Science and Technology Applications"},signatures:"Huaizhi Han, Bingxi Li, Yaning Zhang, Quan Zhu and Ruitian Yu",authors:[{id:"23828",title:"Dr.",name:"Quan",middleName:null,surname:"Zhu",slug:"quan-zhu",fullName:"Quan Zhu"},{id:"148369",title:"Prof.",name:"Bingxi",middleName:null,surname:"Li",slug:"bingxi-li",fullName:"Bingxi Li"},{id:"196928",title:"Dr.",name:"Yaning",middleName:null,surname:"Zhang",slug:"yaning-zhang",fullName:"Yaning Zhang"},{id:"281875",title:"Prof.",name:"Huaizhi",middleName:null,surname:"Han",slug:"huaizhi-han",fullName:"Huaizhi Han"},{id:"282268",title:"Mr.",name:"Ruitian",middleName:null,surname:"Yu",slug:"ruitian-yu",fullName:"Ruitian Yu"}]},{id:"66317",title:"Review Heat Transfer of Non-Newtonian Fluids in Agitated Tanks",slug:"review-heat-transfer-of-non-newtonian-fluids-in-agitated-tanks",totalDownloads:1001,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"The heating and cooling of non-Newtonian liquids in tanks with mechanical impellers are operations commonly employed as chemical reactors, heat exchangers, distillers, extractors, thinners and decanters. In particular, the design of heat exchangers (jackets, helical coils, spiral coils and vertical tubular baffles) in tanks requires the prior knowledge of the rheology of the liquid for the calculation of the convection coefficients and the Reynolds number, in order to obtain the area thermal exchange. This chapter aimed to present the basic concepts of tanks with agitation, non-Newtonian liquids, hydrodynamics, heat transfer and, finally, with a practical design example for engineers and undergraduate students.",book:{id:"7661",slug:"heat-and-mass-transfer-advances-in-science-and-technology-applications",title:"Heat and Mass Transfer",fullTitle:"Heat and Mass Transfer - Advances in Science and Technology Applications"},signatures:"Vitor da Silva Rosa and Deovaldo de Moraes Júnior",authors:[{id:"187128",title:"Ph.D.",name:"Vitor",middleName:null,surname:"Rosa",slug:"vitor-rosa",fullName:"Vitor Rosa"},{id:"188792",title:"Dr.",name:"Deovaldo",middleName:null,surname:"Moraes Júnior",slug:"deovaldo-moraes-junior",fullName:"Deovaldo Moraes Júnior"}]},{id:"65692",title:"Advances in Concentrated Solar Power: A Perspective of Heat Transfer",slug:"advances-in-concentrated-solar-power-a-perspective-of-heat-transfer",totalDownloads:1114,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Solar energy has the potential to reduce the dependence on the dwindling supply of fossil fuels through concentrated solar power (CSP) technology. CSP plants utilize solar thermal energy to produce electrical energy based on different thermodynamic power cycles. Solar collectors, reflectors, receivers, thermal fluid, and turbines are the main components of each CSP plant and involve intensive heat transfer at all stages. This chapter illustrates the thermal characteristics of the main components used in CSP technology. In addition, the solar thermal fluid characteristics and its stable operational ranges are discussed in this chapter. Heat capacity, vapor pressure, volume expansion, density and viscosity of the thermal fluid should not differ significantly at different temperatures during various operation stages because these variations can cause failure in the system, which is designed at the fixed material properties. Currently, CSP technology is associated with a higher cost compared to the electricity generated through gas power plants. Many efforts are made to search for sustainable and inexpensive materials to minimize the cost of CSP. One critical issue faced by CSP technology is the intermittent nature of the sun. Modern CSP plants integrate thermal energy storage (TES) unit to smoothen the power production or to shift the production from peak sunshine hours to peak demand hours.",book:{id:"7661",slug:"heat-and-mass-transfer-advances-in-science-and-technology-applications",title:"Heat and Mass Transfer",fullTitle:"Heat and Mass Transfer - Advances in Science and Technology Applications"},signatures:"Fadi Alnaimat and Yasir Rashid",authors:[{id:"151722",title:"Dr.",name:"Fadi",middleName:null,surname:"Alnaimat",slug:"fadi-alnaimat",fullName:"Fadi Alnaimat"},{id:"291252",title:"Mr.",name:"Yasir",middleName:null,surname:"Rashid",slug:"yasir-rashid",fullName:"Yasir Rashid"}]}],onlineFirstChaptersFilter:{topicId:"954",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:8,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:286,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:106,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:9,numberOfPublishedChapters:101,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:11,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"24",title:"Sustainable Development",doi:"10.5772/intechopen.100361",issn:null,scope:"
\r\n\tTransforming our World: the 2030 Agenda for Sustainable Development endorsed by United Nations and 193 Member States, came into effect on Jan 1, 2016, to guide decision making and actions to the year 2030 and beyond. Central to this Agenda are 17 Goals, 169 associated targets and over 230 indicators that are reviewed annually. The vision envisaged in the implementation of the SDGs is centered on the five Ps: People, Planet, Prosperity, Peace and Partnership. This call for renewed focused efforts ensure we have a safe and healthy planet for current and future generations.
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\r\n\tThis Series focuses on covering research and applied research involving the five Ps through the following topics:
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\r\n\t1. Sustainable Economy and Fair Society that relates to SDG 1 on No Poverty, SDG 2 on Zero Hunger, SDG 8 on Decent Work and Economic Growth, SDG 10 on Reduced Inequalities, SDG 12 on Responsible Consumption and Production, and SDG 17 Partnership for the Goals
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\r\n\t2. Health and Wellbeing focusing on SDG 3 on Good Health and Wellbeing and SDG 6 on Clean Water and Sanitation
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\r\n\t3. Inclusivity and Social Equality involving SDG 4 on Quality Education, SDG 5 on Gender Equality, and SDG 16 on Peace, Justice and Strong Institutions
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\r\n\t4. Climate Change and Environmental Sustainability comprising SDG 13 on Climate Action, SDG 14 on Life Below Water, and SDG 15 on Life on Land
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\r\n\t5. Urban Planning and Environmental Management embracing SDG 7 on Affordable Clean Energy, SDG 9 on Industry, Innovation and Infrastructure, and SDG 11 on Sustainable Cities and Communities.
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\r\n\tThe series also seeks to support the use of cross cutting SDGs, as many of the goals listed above, targets and indicators are all interconnected to impact our lives and the decisions we make on a daily basis, making them impossible to tie to a single topic.
",coverUrl:"https://cdn.intechopen.com/series/covers/24.jpg",latestPublicationDate:"April 24th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:0,editor:{id:"262440",title:"Prof.",name:"Usha",middleName:null,surname:"Iyer-Raniga",slug:"usha-iyer-raniga",fullName:"Usha Iyer-Raniga",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRYSXQA4/Profile_Picture_2022-02-28T13:55:36.jpeg",biography:"Usha Iyer-Raniga is a professor in the School of Property and Construction Management at RMIT University. Usha co-leads the One Planet Network’s Sustainable Buildings and Construction Programme (SBC), a United Nations 10 Year Framework of Programmes on Sustainable Consumption and Production (UN 10FYP SCP) aligned with Sustainable Development Goal 12. The work also directly impacts SDG 11 on Sustainable Cities and Communities. She completed her undergraduate degree as an architect before obtaining her Masters degree from Canada and her Doctorate in Australia. Usha has been a keynote speaker as well as an invited speaker at national and international conferences, seminars and workshops. Her teaching experience includes teaching in Asian countries. She has advised Austrade, APEC, national, state and local governments. She serves as a reviewer and a member of the scientific committee for national and international refereed journals and refereed conferences. She is on the editorial board for refereed journals and has worked on Special Issues. Usha has served and continues to serve on the Boards of several not-for-profit organisations and she has also served as panel judge for a number of awards including the Premiers Sustainability Award in Victoria and the International Green Gown Awards. Usha has published over 100 publications, including research and consulting reports. Her publications cover a wide range of scientific and technical research publications that include edited books, book chapters, refereed journals, refereed conference papers and reports for local, state and federal government clients. She has also produced podcasts for various organisations and participated in media interviews. She has received state, national and international funding worth over USD $25 million. Usha has been awarded the Quarterly Franklin Membership by London Journals Press (UK). Her biography has been included in the Marquis Who's Who in the World® 2018, 2016 (33rd Edition), along with approximately 55,000 of the most accomplished men and women from around the world, including luminaries as U.N. Secretary-General Ban Ki-moon. In 2017, Usha was awarded the Marquis Who’s Who Lifetime Achiever Award.",institutionString:null,institution:{name:"RMIT University",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. 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He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. 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Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}}]},{type:"book",id:"7978",title:"Vitamin A",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7978.jpg",slug:"vitamin-a",publishedDate:"May 15th 2019",editedByType:"Edited by",bookSignature:"Leila Queiroz Zepka, Veridiana Vera de Rosso and Eduardo Jacob-Lopes",hash:"dad04a658ab9e3d851d23705980a688b",volumeInSeries:3,fullTitle:"Vitamin A",editors:[{id:"261969",title:"Dr.",name:"Leila",middleName:null,surname:"Queiroz Zepka",slug:"leila-queiroz-zepka",fullName:"Leila Queiroz Zepka",profilePictureURL:"https://mts.intechopen.com/storage/users/261969/images/system/261969.png",biography:"Prof. Dr. Leila Queiroz Zepka is currently an associate professor in the Department of Food Technology and Science, Federal University of Santa Maria, Brazil. 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The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. 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