Normal physiological changes of ageing.
\r\n\tThere will be a chapter on secondary causes of sexual dysfunction disorders related to diabetes, cardiovascular disease, and obesity. A chapter on remedial measures to enhance sexual activity and maintain human relationships will be discussed. As there is a growing number of cancer survivors a chapter on cancer-related sexual dysfunction will be welcomed for including it.
",isbn:null,printIsbn:null,pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"b988fda30a4e2364ee9d47e417bd0ba9",bookSignature:"Dr. Dhastagir Sultan Sheriff",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11889.jpg",keywords:"Sex, Sexual Response Cycle, Erection, Premature Ejaculation, Libido, Orgasm, Painful Intercourse, Psychological, Female, Lack of Desire, Erectile Disorders, Pain Disorders",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 8th 2022",dateEndSecondStepPublish:"May 6th 2022",dateEndThirdStepPublish:"July 5th 2022",dateEndFourthStepPublish:"September 23rd 2022",dateEndFifthStepPublish:"November 22nd 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Dhastagir Sultan Sheriff is a life member of the European Society for Human Reproduction and Early Human Development, Association of Physiologists and Pharmacologists of India, member of the National Academy of Medical Sciences, New Delhi, and resource person for UNESCO for Medical and Bioethics. Dr. Sheriff has authored five books including a textbook on medical biochemistry with additional interest in human sexology. He has done extensive research in andrology, sex education, and counseling.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"167875",title:"Dr.",name:"Dhastagir Sultan",middleName:null,surname:"Sheriff",slug:"dhastagir-sultan-sheriff",fullName:"Dhastagir Sultan Sheriff",profilePictureURL:"https://mts.intechopen.com/storage/users/167875/images/system/167875.jpg",biography:"Dhastagir Sultan Sheriff is a life member of the European Society for Human Reproduction and Early Human Development, Association of Physiologists and Pharmacologists of India, member of the National Academy of Medical Sciences, New Delhi, and resource person for UNESCO for Medical and Bioethics. Dr. Sheriff has authored five books including a textbook on medical biochemistry with additional interest in human sexology. He had editorials written in the British Journal of Sexology, Journal of Royal Society of Medicine, Postgraduate Medicine, and Scientist. 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Thus, they are more vulnerable and could easily decompensate with minor stressors, resulting in increased frailty. There are established detrimental effects of hospitalisation on older adults and about 17% of older medical patients who were independently mobile 2 weeks prior to hospital admission required assistance to walk at hospital discharge [3, 4]. Therefore, to improve outcomes for frail older people with multiple co-morbidities and an acute illness, admission should be to an Emergency Frailty Unit (EFU), a separate unit within an AMU but led by a geriatrician and the multidisciplinary team (MDT) to provide comprehensive person-centred care.
\nThe clinical assessment of frail older people is challenging, as they often have multiple co-morbidities and diminished functional and physiological reserves. In addition, the physical illness or adverse effects of drugs are more pronounced resulting in atypical presentation, cognitive decline, delirium or inability to manage routine activities of daily living (ADLs) [5]. Among the potential adverse outcomes for frail older inpatients, are the risks of continued deterioration as a consequence of medical complications such as pressure sores, hospital-acquired infections or functional decline. This can also lead to long-term increased dependency, institutionalisation and death.
\nHospitals face a rising demand from an increasing number of acute emergency admissions of people aged 65 years and above with multiple co-morbidities and psychosocial problems. The admission rates for people over 65 years are three times higher than for people aged 16–64 years. Older patients cannot always be transferred quickly from the hospital after acute illness and on average hospital length of stay (LoS) is significantly higher than for under 65 years [6]. The older people occupy around two-thirds of acute hospital beds and emergency admissions have been rising for several years [7]. The healthcare cost and the proportion of hospital bed days used by older people are likely to increase further due to ageing population [8].
\nThe normal physiological changes occur with ageing in all organ systems (Table 1) and this has implications for the clinical assessment of older people [9–11]. Therefore, it is essential to be aware of these changes as these have an impact on drug metabolism and pharmacodynamics. In addition to comprehensive geriatric assessment (CGA), these changes can be delayed or reversed with appropriate diet, exercise and medical intervention.
\n\n | Change in physiology | \nImpact on health | \n
---|---|---|
Cardiovascular | \n↓ Heart rate and cardiac output \n↓ Arterial compliance \n↑ Systolic blood pressure \n↑ Myocardial irritability \n↓ Tissue perfusion \n↑ Circulation time \n | \nEasy fatigability and loss of stamina for physical work \nPeripheral oedema \nIsolated systolic hypertension \nDysrhythmias \nCold sensitivity in the hands/feet \n | \n
Nervous system | \n↓ Normal reflexes \n↓ Proprioception \n↓ Baroreceptor response \n↓ Sympathetic response \n↑ Sensitivity to | \nImpaired cognition \nFalls \nPostural hypotension \n | \n
Sensory | \n↓ Salivation and taste \n↓ Thirst \n↓ Response to pain \n↓ Visual acuity and ↓ Hearing \n | \nAspiration \nDehydration \nFalls \nIncreased isolation and depression \n | \n
Lungs | \n↓ Tidal volume \n↓ Vital and total lung ↓ Lung compliance \n↓ Response to hypoxemia \n↑ Residual volume \n | \nLow oxygen saturations | \n
Kidneys | \n↓ Glomerular filtration ↓ Renal flow and kidney | \nHigher chance of drug side effects due to reduced renal clearance (serum creatinine level remains relatively constant due to reduced muscle mass and reduced creatinine production) | \n
Bladder | \nSmaller voided volume \n↓Bladder capacity \n↑ Involuntary detrusor ↑ Residual volume \n | \nUrinary incontinence \nUrgency \nOveractive bladder symptoms \n | \n
Gastrointestinal | \n↓ Gastric emptying \n↓ Bowel movements \n↓ Transit time and ↓ Liver mass ↓ Sense of thirst \n↓ Capacity to conserve | \nWeight loss \nConstipation \nSlower drug metabolism and reduced hepatic first-pass effect, thus increased bioavailability \nDehydration \n | \n
Endocrine | \n↓ Insulin sensitivity \nThyroid impairment \n↓ Metabolic rate \n↓ Temperature ↓ Bone mineral density \n | \nHyperglycaemia during acute illness \nRisk of hypothermia \nOsteopenia/fragility fractures \n | \n
Body composition | \nAtrophy of skin epidermis \n↓ Subcutaneous fat \n↓ Sweat glands \nAtrophy of muscle cells \nDegenerative changes in | \nEasy bruising \nPressure ulcers \nDry skin \nSarcopenia \nFalls \n | \n
Immune system | \n↓ Neurohumoral response ↓ T-cell response | \nHigher infection rate Higher probability of infection \n | \n
Normal physiological changes of ageing.
The holistic assessment of older people is best achieved by the MDT. The MDT members include doctors, nurses, physiotherapist (PT), occupational therapist (OT), dietician, clinical pharmacist, social worker (SW), specialist nurses (e.g. tissue viability nurse and Parkinson’s disease nurse specialist), hospital discharge liaison team and carers. Input from a clinical psychologist or old age psychiatrist may be needed depending on individual patients’ needs. All members engage with patients and carers to complete their assessments and intervention, followed by multidisciplinary meeting (MDM) to formulate ongoing care plan and follow-up.
\nThe medical assessment begins at the time of admission to an AMU or an EFU with the appropriate investigations and thus establishing the relevant diagnosis. In addition to treating acute illness, there must be an attempt to optimise the symptoms and treatment of chronic diseases [12]. The common medical diseases among older people are listed in Table 2. A carer or a relative usually accompanies an older patient to the hospital, and a short conversation with them can rapidly reveal the diagnosis and direct ongoing management.
\nMostly seen in older people | \nAlzheimer’s disease \nNormal pressure hydrocephalus \nTemporal arteritis (giant cell arteritis) \nDiastolic heart failure \nInclusion body myositis \nAtrophic urethritis and vaginitis \nShingles (herpes zoster) \nBenign prostatic hyperplasia \nAortic aneurysm \nPolymyalgia rheumatica \n | \n
Common in older age group | \nDegenerative osteoarthritis \nOveractive bladder with urinary incontinence \nDiabetic hyperosmolar nonketotic coma \nFalls and fragility hip fracture \nOsteoporosis \nParkinsonism \nAccidental hypothermia \nPressure ulcers \nProstate cancer \nStroke \nGlaucoma and cataract \nMonoclonal gammopathies \n | \n
Common medical diseases among older people.
Older people admitted to the hospital with an acute illness often a non-specific presentation, which can obscure the serious underlying pathology or medical diagnosis. For example, acute bowel infarction in older people may not present with typical abdominal pain or tenderness or lack of typical signs on meningism in bacterial meningitis. The atypical presentation in older people could be one or combination of ‘feeling unwell’, ‘inability to cope’, ‘off-legs’, ‘fall’, ‘confusion’, ‘dizziness’, ‘incontinence’, ‘weight loss’, etc. The atypical presentation with possible background sensory impairment, lack of collateral history, polypharmacy and high prevalence of cognitive deficits limits good clinical assessment.
\n‘Feeling unwell’ or ‘inability to cope’ could be a presentation of an acute infection, exacerbation of underlying chronic disease (e.g. chronic heart failure), drug side effect (e.g. constipation) or dehydration. However, this could be due to underlying malignancy; therefore, such a presentation warrants good clinical examination and appropriate investigations.
\nWorldwide, falls are the second most common cause of unintentional injury and death. A non-accidental fall is a complex system failure in the human organ system, where a person comes to rest on the ground from a standing or a sitting height, unintentionally with no associated loss of consciousness [13]. The prevalence of falls increases with age, and oldest old is at highest risk. One-third of older adults over 65 years and half of older people above 80 years could experience one fall in a year [14, 15].
\nFalls are most common in institutionalised older people [16] and half of the fallers will fall again within a year [17]. Older people with high risk of falls are sometimes admitted to the hospital to avoid future falls but in reality, hospitals are associated with a higher risk of falling due to several new risk factors such as unfamiliar environment, increased risk of delirium, high beds, single rooms and so on [18, 19]. Falls are associated with a threefold increased risk of future falls, fear of falling, prolonged hospital stay, functional decline, increased dependency, institutionalisation, increased expenditure, morbidity and mortality [20, 21]. Falls result in injury (4%) and fragility hip fracture (1%), following which up to 10% of people will die within a month, a third dying during the following year after [22].
\nThe evaluation of falls begins by distinguishing it from brief sudden loss of consciousness (syncope). However, it could be challenging to do so in certain cases but every effort should be made. Falls cannot only be simply related to underlying medical or neurological disorder as falls are usually multifactorial including a wide range of intrinsic and extrinsic factors. The most common factors leading to falls in neurological patients are the disorder of gait and balance (55%), epileptic seizures (12%), syncope (10%), stroke (7%) and dementia. Falls have particularly being linked to Parkinson’s disease (62%), polyneuropathy (48%), epilepsy (41%), spinal disorders (41%), motor neuron disease (33%), multiple sclerosis (31%), psychogenic disorders (29%), stroke (22%) and patients with a pain syndrome (21%) [16]. Dementia is associated with impaired mobility and is an independent risk factor for falling [23]. People who present with a fall or report recurrent falls in the past year or demonstrate abnormalities of gait and/or balance should have multifactorial, multidisciplinary assessment for falls, risk factors, perceived functional abilities and fear of falling. In addition, bone health and history of previous fragility fractures should be explored [24].\n
\n‘Delirium’ is a common syndrome affecting older people admitted to AMU or EFU. It is a serious acute problem which has been best understood as an ‘acute brain dysfunction’ or an ‘acute confusional state’ characterised by a rapid onset of symptoms, fluctuating course and an altered level of consciousness, global disturbance of cognition or perceptual abnormalities. The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) defines delirium as ‘a disturbance of consciousness that is accompanied by a change in cognition that cannot be better accounted for by a pre-existing or evolving dementia’ [25].
\nThe diagnosis of delirium is based on clinical observations, cognitive assessment, physical and neurological examination. Despite the common problem, delirium remains a major challenge and often under-diagnosed and poorly managed. Clinically, delirium can be divided into hyperactive, hypoactive or mixed forms, based on psychomotor behaviour. The Confusion Assessment Method (CAM) supports a diagnosis of delirium if there is a history of acute onset of confusion with a fluctuating course and inattention in the presence of either disorganised thinking and/or altered level of consciousness [26]. Collateral history from the family member or carers is helpful to detect a recent change in cognition.
\nDelirium usually occurs as a result of complex interactions among multiple risk factors such as cognitive impairment, Parkinson’s disease, stroke, poor mobility, history of previous delirium, hearing or visual impairment, malnutrition or depression. It is often precipitated in the hospital setting due to acute medical illnesses including infection, acute coronary syndrome, bowel ischaemia, surgical disorder, polypharmacy, pain, dehydration, electrolyte imbalance, new environment, sleep deprivation, constipation, hypoxia, use of restraints or indwelling catheters.
\nDelirium, if not recognised early and managed appropriately, can result in poor outcomes, including prolonged hospital stay, increased functional dependence, institutionalisation, a risk of developing dementia, increased inpatient and post-discharge mortality [27–29]. Therefore, an older person admitted to hospital with confusion should be promptly assessed for delirium to improve clinical outcomes. The optimal assessment should be completed to identify underlying modifiable risk factors and treating precipitating factors, followed by reorientation and restoration of cognitive functions using non-pharmacological strategies including carer support and education, good communication among MDT and appropriate follow-up. The pharmacological drugs including haloperidol or risperidone should be used to manage severe agitation or behavioural disturbance.
\n‘Dementia’ is often recognised for the first time as an incidental condition when people are admitted to an acute hospital for another reason. More than one-third of acute medical admissions (42.4%) for over 70s have been reported to have dementia and only half of which were diagnosed prior to admission [30]. However, dementia can be misdiagnosed as an acute illness and can be accompanied by reversible cognitive decline. In addition, older people with known dementia who present with an altered mental state can be mislabelled as having progressed to another stage of dementia missing undiagnosed delirium. Older people with cognitive impairment are at increased risk of falls [31] and are also more likely to die during hospitalisation, and increased severity of cognitive impairment is associated with higher odds of mortality (from 2.7 in those with moderate impairment to 4.2 in those with severe impairment) [32]. Therefore, older people in hospital settings should be carefully assessed for underlying cognition. Dementia is a chronic progressive brain disorder marked by a disturbance of more than two domains of brain functions for more than 6 months. The various cognitive deficits may include short-term memory loss, language- or word-finding difficulties, mood and personality changes, impaired reasoning, learning new skills, inability to concentrate, plan or solve problems, difficulty in taking decisions or completing a task, disorientation, visuospatial difficulties or problems with calculations. Dementia is the most appropriate diagnosis when two or more cognitive deficits have an impact on ADLs or social interaction, often associated with behavioural and psychological symptoms of dementia (BPSD) [33].
\n‘Frailty’ is defined variably and there is no single generally accepted definition. Fried et al. [34] reported a clinical definition of frailty based on the presence of three or more frailty indicators: unintentional weight loss, slow walking speed, subjective exhaustion, low grip strength and low levels of physical activity. Frailty, based on these criteria, was predictive of poor outcome including institutionalisation and death [34]. Whereas Rockwood and Mitnitski [35] had advocated an alternative approach to frailty by considering frailty in relation to the accumulation of deficits with age, including medical, physical, functional, cognitive and nutritional problems. The frailty index expresses the number of deficits identified in an individual as a proportion of the total number of deficits considered. Higher values indicated a greater number of problems and hence greater frailty. For example, if 40 potential deficits were considered, and 10 were present in a given person, their frailty index would be 10/40 = 0.25 [36]. A valid index can be derived from the routine information collected on CGA [37–39]. Therefore, the presence of frailty on clinical judgement should prompt consideration to holistic assessment by MDT.
\nOlder people usually have more than five medical conditions and one pathological disorder in an organ, which can weaken another system. This results in increased disability, physical dependence, functional deterioration, isolation or even death. Long-term conditions in older people require very careful assessment and monitoring particularly whilst undergoing acute medical treatment in the hospital. Every older person admitted to MAU or EFU should have assessment of underlying chronic medical conditions, including ischaemic heart disease, heart failure, chronic respiratory diseases, chronic inflammatory and autoimmune problems. Modifiable cardiovascular risk factors such as diabetes mellitus, hypercholesterolemia, hypertension, obesity, excessive smoking or alcohol consumption should be reviewed and optimally addressed.
\nMany people with long-term physical health conditions also have mental health problems [40]. Mental health problems are common in older people, and 8–32% of patients admitted to acute hospitals were found to be depressed [41, 42]. Depression is not a natural part of ageing but can be easily missed in older patients, thus resulting in adverse outcome including delayed recovery and suicide. It is often reversible with early recognition and prompt intervention. Delirium has been reported in 27% of older patients above 70 years [41]. The prevalence of dementia in acute hospitals was reported as 48% in men and 75% in women older than 90 years [30].
\nThe current service models for the provision of mental health input in general medical care wards are variable. The prevailing view in the United Kingdom is that old age psychiatrists have the main responsibility for the diagnosis and management of dementia and other mental health problems. In many hospitals, both psychiatric and medical notes are not easily accessible and are mostly kept separately [43].
\nThe National Service Framework (UK) for older people was published in 2001—standard seven aims to promote good mental health in older people and to treat and support those older people with dementia [44]. The liaison mental health services have not only shown improved clinical outcomes as measured by the length of hospital stay or discharge to original residence but also suggested cost effective models. However, concerns have been raised about the reliability and validity of the various studies included in this systematic review [45]. The hospital liaison multidisciplinary mental health team is the model advised in the United Kingdom to offer a general hospital a complete service.
\nThe Rapid Assessment Interface and Discharge (RAID) service model is an example in the United Kingdom where a psychiatry liaison service provides MDT input to acutely unwell older people with existing mental health admitted to hospital [46]. The RAID service has shown to be an effective, enhanced service model for older people who are at risk for dementia or other mental health problems and has shown good outcomes with quality improvements in the care of older people [46].
\nCollateral history from the family or carers remains the key feature for initial assessment. If dementia is suspected in a person, a full medical assessment must be completed, an example being the British Geriatrics Society’s guidance on CGA of the frail older people [12]. Older people in the hospitals should be assessed for mood, anxiety and depression. The hospital anxiety and depression scale (HADS) is a simple, valid and reliable tool for use in hospital practice [47]. It is a self-assessment screening tool, which warrants further assessment based on abnormal scores. The score for the entire scale for emotional distress can range from 0 to 42, with higher scores indicating more distress. Score for each subscale (anxiety and depression) can range from 0 to 21 (normal 0–7, mild 8–10, moderate 11–14, severe 15–21) [48]. A short-form Geriatric Depression Scale (GDS) consisting of 15 questions can be used for depression [49]. Any positive score above 5 on the GDS short form should prompt a detailed assessment and evaluation. Generalised anxiety disorder (GAD) is the most common mental disorder encountered in older patients and is often accompanied by depression. It could be helpful to assess older person’s emotional state and sense of well-being as they may report psychological burden of the disease, for example, fear of falling or fear of being in the hospital which is associated with loss of independence by older people. History of delusions and hallucinations or previous use of psychotropic drugs may suggest a mental health problem. Patient’s permission should be sought before interviewing their relatives or carers for collateral history.
\nFollowing initial suspicion or diagnosis of a mental health problem in older people, a more collaborative work between physicians and old age psychiatrists for the prompt diagnosis and management of mental health problems will improve outcome [46].
\nDrug prescribing increases with both age and incidence of co-morbidities [50, 51]. Polypharmacy is defined as use of either five or more concurrent medications or, at least, one potentially inappropriate drug. Half of older people aged between 65 and 74 years and two-thirds of those aged 75 years and over are affected by polypharmacy including conventional and complementary medicines [52]. Polypharmacy is associated with adverse outcomes including hospital admissions, falls, delirium, cognitive impairment and mortality [53, 54]. Although drugs have an important role in managing co-morbidities, it is not without harm and adverse outcomes [55].
\nThere is conflicting evidence that psychotropic medications are associated with higher falls in people with dementia [56, 57] though there is clear evidence that there is associated increased fall risk in cognitively intact people [58]. Other classes of drugs including Parkinson’s disease drugs, anticonvulsants, steroids and fluoroquinolone can result in acute confusion [59]. Drug interactions could impair electrolytes, cause postural hypotension, hypothermia, gait disorder or gastrointestinal disturbance, resulting in prolonged hospital admission [55].
\nTherefore, all older inpatients should have drug review and withdrawal of any possible offending agent if practical would be logical. This can be based on screening tool of older persons’ prescriptions (STOPP), and a tool to alert doctors to commence appropriate treatment (START) criteria should be used [60]. Patients should also be assessed for their ability to manage their drugs, understanding of drug, dexterity and vision. At the same time, appropriate new medications if deemed necessary and evidence-based should be commenced. Older people with cognitive impairment should be prescribed with greater care, adhering to the principle of‚ ‘starting low and going slow’ [61].
\nGait and balance are regulated by both central and peripheral nervous system; thus, various neurological disorders can result in postural instability and poor mobility. Balance system can be affected by the impact of neurological disease on postural responses, postural tone, sensory feedback, visuospatial disorder, executive dysfunction or delayed latencies. Gait disorders have been classified into lower (e.g. peripheral), middle (e.g. spinal, basal ganglia) and higher level gait disorders (e.g. frontal or psychogenic) [62]. The more pragmatic approach could be used to describe gait disorders including hypokinetic gait disorders, dystonic, hemi- or paraparetic gait, ataxia, vestibular, neuromuscular and psychogenic gait [62]. All components of gait including initiation of walking, step length, coordination, walking speed, symmetry, stride width, rhythm and posture should be assessed. Various tools/scales can be used for further assessment of gait and balance (Table 3). Most physicians work closely with PT and rely on their assessment of patient’s needs in relation to mobility, balance and posture. Multidimensional assessment and multiagency management of mobility in older people lead to better outcomes.
\n\n | Technique | \nNormal values | \n
---|---|---|
Turn 180° [63] | \nA measure of dynamic postural stability, asking a patient to take few steps and then turn around by 180° to face opposite direction. Count the number of steps taken to complete a 180° turn | \nFive or less steps | \n
3-m TUG test [64] | \nA measurement of mobility. A person is asked to stand up from seated position, walk for 3 m, turn and walk back to a chair and sit down. Measure the time taken in seconds | \n12 or fewer seconds, can vary with age by 2–4 s | \n
Near tandem stand [65] | \nA measure of balance and ankle strength. A person is asked to stand in a near tandem position with their bare feet separated laterally by 2.5 cm with the heel of the front foot 2.5 cm anterior to the great toe of the back with their eyes closed. A person can hold arms out or move the body to help keep the balance but do not move the feet | \nAble to stand >30 s with eyes closed | \n
Alternate step test [66] | \nA measure of strength, balance, coordination and stair climbing. It provides a measure of mediolateral stability. A person should be asked to place alternate whole left and right bare foot onto a 19-cm high stepper for a total of eight times | \n10 or fewer seconds, can vary with age by 2–4 s | \n
Sit-to-stand test [67] | \nA measurement of functional mobility, balance and lower limb strength. A person should be able to stand up and sit down five times with crossed arms from a 45-cm straight-backed chair | \n11.4 s (60–69 years); 12.6 s (70–79 years); 14.8 s (80–89 years) | \n
Gait and balance assessment tools.
Physical activity interventions for people with an intact cognition are well documented and shown to be effective in improving balance and reducing falls. People with dementia are two to three times more likely to fall [16] and risk is further increased in people with Lewy body dementia (LBD) and Parkinson’s disease dementia (PDD) [23, 68]. There is limited evidence showing significant gait and balance improvement following the targeted exercise programme in the community-dwelling older people with dementia [69]. More recently, it has been shown that supervise exercise training in people with dementia living in community could improve muscle strength and physical activity [70]. There is dearth of similar studies in the hospital setting and further research is required. A simple flexible home-based muscle strengthening and balance-training exercise programme along with medication could improve the physical performance in the older people.
\nIt is not uncommon for older people to be admitted to the hospital with functional deterioration or increased dependence, thus unable to cope. Older people admitted to the hospital with an acute medical problem, ‘geriatric giants’ [71, 72], incontinence, immobility, postural instability (falls) and intellectual impairment (dementia) or who are frail with one or more disability should get an appropriate functional assessment. A typical geriatric assessment for such people should begin with a review of their functional status. This is usually captured in two commonly used functional status measurement—basic ADL and instrumental ADL (IADL). The ADL that is initially affected includes complex or IADLs such as shopping, handling finances, driving, cooking or using the telephone followed by basic ADL including bathing, dressing, toileting, transferring, continence or feeding. Whether patients can function independently or need some help is usually determined by OT, as part of the comprehensive geriatric assessment. OTs work closely with the physiotherapists to assess patient’s own environmental and home status with the identification of appropriate equipment and its delivery before discharge. In addition to optimising functional independence, OT intervention also enhances home comfort, safe use of available facilities, safe access to transport or potential use of telehealth technology and local resources.
\nThe assessment of functional limitations is best completed by an interview with the person and caregiver with open-ended questions about their ability to perform activities. They can further be assessed by direct observation either in their usual place of residence or whilst performing a routine activity, for example, toilet use. The functional status can also be assessed using a standardised assessment instrument with questions about specific ADLs and IADLs. There are more than 15 validated scales to complete functional assessments including Katz index of independence in activities of daily living [73], the modified Blessed dementia scale [74], the instrumental activities of daily living scale [75], the Functional Assessment Questionnaire [76], Functional Assessment Staging Test [77], Barthel Activities of Daily Living Index Scale [78], Alzheimer’s Disease Co-operative Study-Activities of Daily Living Inventory [79], Disability Assessment for Dementia [80] and Bristol activities of daily living [81].
\nThe functional scales can detect early functional impairment and often help discriminate mild dementia in comparison to those with no cognitive impairment. The scales that assess complex social functional activities are better in detecting dementia compared to those scales that involve basic ADLs [82]. A good timely recognition of functional difficulties may arrest further decline, postponing the need for care-home placement. The functional assessment scales can only provide a guidance and these scales are commonly used to assess the treatment efficacy in scientific research studies.
\nUrinary incontinence (UI) is defined by the International Continence Society as ‘the complaint of any involuntary leakage of urine’. Older people may assume that UI is a normal consequence of ageing and often may not be reported. UI is a common problem and older people may feel embarrassed to discuss the problem and avoid evaluation. Incontinence is associated with social isolation, institutionalisation and medical complication including skin irritation, pressure sores, recurrent infections and falls. The prevalence of urinary incontinence depends on the age and gender; for older women, the estimated prevalence of urinary incontinence ranges from 17 to 55% (median = 35%, mean = 34%). In comparison, incontinence prevalence for older men ranges from 11 to 34% (median = 17%, mean = 22%) [83].
\nThere is a strong association of faecal incontinence (FI) with age; FI increases from 2.6% in 20–29-year-old up to 15.3% in 70 years or above [84]. In hospital settings, UI can be an atypical presentation and is a risk factor for adverse outcomes. The aetiology of incontinence in older people is often multifactorial. People with cognitive impairment usually encounter UI and later FI. Older people often find it difficult and challenging to express the need of regular toilet use, and as dementia progresses, it could be difficult to identify toilet or use it appropriately. Incontinence and inability to use toilet independently can be frustrating and distressing, which may lead to psychological burden, isolation, immobility or institutionalisation.
\nTherefore, a good continence assessment should be an essential component for any older people admitted to hospital to ensure good-quality person-centred care, promoting independent living. Assessment of precipitating factors and identification of treatable, potentially reversible conditions are essential steps. Continence problems can be secondary to drug side effects, constipation, impaired mobility, arthritic pain, inappropriate clothing or dexterity.
\nA good clinical history could categorise UI as stress UI (involuntary urine leakage on exertion), urgency UI (a sudden compelling desire to urinate) or mixed UI (involuntary urine leakage associated with both urgency and exertion). Overactive bladder (OAB) is defined as urgency that occurs with or without incontinence and usually with frequency and nocturia. Bladder diary (72-h urine frequency volume chart) and pre- and post-void bladder scan support clinical diagnosis. Vaginal inspection is helpful to exclude vaginal atrophy, prolapse or infections. Older people with FI should have an anorectal examination to exclude faecal loading, lower gastrointestinal cancer, rectal prolapse, anal sphincter problems or haemorrhoids. Neurological causes of cauda equina syndrome, frontal lobe tumours, neurodegenerative disorders or stroke could also result in UI or FI.
\nThe continence problems can be minimised by promoting regular toilet use, appropriate toilet adaptations and providing walking aids to improve accessibility to toilet. Nocturnal incontinence remains a challenging situation but can be managed using various containment methods or limiting fluid intake in the evening. Drug treatment after specialist continence assessment is usually the next step if non-drug measures failed to provide symptomatic benefits. The aim should be to treat the underlying cause but people who continue to have episodes of UI or FI after initial management should be considered for specialised management.
\nOlder people admitted with an acute illness are at increased risk of weight loss and this remains a challenge for the teams in the hospital setting. Acute illness can result in loss of appetite, and management of an acute illness may take priority, therefore making older people more vulnerable in the hospitals, particularly those with cognitive impairment or those who cannot communicate their needs. The National UK Dementia Audit Report in 2013 showed that nutritional assessments were undertaken in less than 10% of patients in some hospitals [85].
\nA detailed nutritional assessment should be undertaken on admission to hospital and should include any recent weight loss, dietary intake and habits. The risk factors including dry mouth, poor oral hygiene, problems with dexterity, reduced vision, acute or chronic confusion, constipation or pain should be explored and actively managed to avoid poor nutrition. Regular nutritional assessments using Malnutrition Universal Screening Tool (MUST) can be helpful and this has been validated to be used by any health professional in the hospital. It is a five-step screening tool, which can identify those who are at risk of weight loss or are malnourished [86].
\nA collective and simple approach with involvement of family and carers can prevent malnutrition during hospitalisation. Patients should be offered small frequent meals and regular snacks or preferred food is often helpful. Protected meal times and regular prompting or assistance for those with cognitive impairment can lead to improved food intake [87].
\nHigher levels of poor oral health can be commonly observed and it is challenging to provide good and regular oral hygiene care to older people in hospitals. The oral hygiene in older people can be compromised secondary to impaired sensory functions, reduced physical dexterity and functional dependence. Older people are often on polypharmacy including anticholinergics, diuretics, antidepressants and antipsychotics. The common side effects of drugs are reduced salivary flow, which could affect the efficiency of chewing, leading to dental problems. Older people with cognitive deficits are at higher risk of developing oral diseases and conditions including dental caries, dental plaques and missing teeth [84]. Poor oral hygiene can also be related to uncontrolled diabetes, inappropriately fitted dentures, lack of teeth, poor mobility or salivary gland dysfunction [88].
\nOral Health Assessment Tool (OHAT) screening has been proposed for the timely assessment of oral and dental hygiene. This tool has been validated for use by nursing staff in care-home residents [89] also those with dementia [90]. There could be reluctance and resistivity to maintain basic good oral hygiene by choice or lack of knowledge/information. Enhanced engagement of carers with oral hygiene strategies, a good education on oral hygiene in older people and timely identification of oral health problems by regular dental consultations could be effective in preventing oral diseases.
\nOlder people, in general, are at higher risk of skin problems including pruritus, eczematous dermatitis, purpura, venous insufficiency and pressure ulcers. Other risk factors include loss of protective fat, malnutrition, frailty, sarcopenia, urinary or bowel incontinence and cognitive impairment. The risk of pressure ulcers further increases with hospitalisation secondary to poor oral intake and reduced physical activities.
\nPrompt assessment and appropriate skin-care plan including good personal hygiene, healthy balanced diet, avoiding excessive heat and friction, promoting continence and early mobilisation are the key factors to minimise the risk of skin breakdown.
\nVisual impairment is common in older people and this risk increases with advancing age. The visual impairment increases from 6.2% at ages 75–79 to 36.9% at age 90 or over [91]. Blindness also increases from 0.6 (75–79) to 6.9% in 90 years or over. Visual impairment in older people is often under-diagnosed and can complicate the accurate assessment of ADLs. Older people who experience visual problems may avoid activities that require good vision and become isolated or even need to be institutionalised. People with cognitive impairment may further experience visuoperceptual difficulties such as visual hallucinations, colour perception, background contrast and depth perception.
\nSimple measures such as the use of blinds or shades to reduce glare, wearing the correct glasses, minimising visual and physical obstacles, using colours and contrasts to mark different areas, assistive technologies such as automatic lights, audio labels or audio books can minimise the risks. Requesting eyesight testing by involving optometrists or ophthalmologists to examine eyes for the causes of sight loss is a first step in defining appropriate interventions.
\nHearing impairment is one of the three most common chronic diseases along with arthritis and hypertension [92]. People with hearing loss are less likely to participate in social activities and are less satisfied with their life as a whole. Hearing loss does not only affect individual’s emotional well-being but also their ability to manage IADLs. Older people with hearing loss are prone to develop dementia [93] and hearing loss is commonly reported in people with dementia.
\nHearing loss can be conductive and sensorineural. The causal factors that may contribute to hearing impairment could include ear wax build-up, ear infections, degenerative ageing process, excess occupational noise, stroke, head injuries, drug side effects or neoplasms like an acoustic neuroma.
\nAll patients with hearing impairment require thorough examination and presence of dementia should not preclude assessment for a hearing aid. Simple measures such as speaking in a normal tone, giving attention and making eye contact are helpful. Appropriate seating, eliminating background noise and repeating the key phrases or summary points improve communication. Hearing aids are often useful, though they do not improve cognitive function or reduce BPSD but has shown that patients improved on global measures of change [94].
\nPain should be treated as a fifth vital sign. Pain assessment involves holistic evaluation of the person on the first presentation of pain and then following up with regular pain assessment. Pain assessment should include the site of pain, type, precipitating factors and impact of pain on the individual. Physical assessment should be performed for any skin bruise or infection, constipation, reduced range of joint movement, vertebral tenderness, recent injury or fracture. There are several pain scales available, visual analogue scale or the numerical rating scales are most useful.
\nOlder people with cognitive impairment and those who cannot verbally communicate their symptoms particularly pain, observation or collateral information from relative or carer or suggestion of change in person’s behaviour could help to assess the severity of pain [95]. The numeric pain-rating scale (0–10, where 10 being most severe pain) is often used in routine clinical practice. The specific pain-screening tools such as ‘Assessment of Discomfort in Dementia (ADD)’ are available to be used in patients with cognitive impairment. The tool involves assessing pain history, physical examination and administration of analgesics and giving analgesics as needed [96].
\nIt is important to assess person’s language, ethnic background, cultural beliefs, personality, education, family experience, socio-economic status and life experience to complete assessment holistically and provide person-centred care. A detailed assessment of social network, daytime activities and informal support available from family or friends should be done on the first day of admission to the hospital.
\nA prompt, patient-centred identification of the requirement of social services input helps with safe timely discharge to the most suitable and friendly environment. Social Worker (SW) should ideally be allocated if a need for social services is anticipated at the time of hospital admission. Once all the needs of the patient are identified, SW should be contacted to organise formal carers or care-home placement if the patient is not suitable for home discharge.
\nThe quality of life (QoL) assessment was almost unknown 20 years ago but it is now an established fact that the psychological burden of an illness cannot be described fully by measures of disease status. It has been acknowledged that various psychosocial factors such as apprehension, anxiety, restricted mobility, difficulty in fulfilling ADLs and the financial burden must also be addressed to complete holistic assessment of older people. The most important constituents of the quality of life in older age from older people’s perspective are having good social relationships with family, friends and neighbours; participating in social and voluntary activities and individual interests and having good health and functional ability [93, 94]. Other measures of good QoL include living in a good home and neighbourhood, having a positive outlook and psychological well-being, having an adequate income and maintaining independence and control over one’s life [97, 98].\n
\nThe assessment of a patient’s experience of disease and its effect on their quality and outcome framework (QoF) should be one of the central components of healthcare assessment to acknowledge safe and early hospital discharge. The family members should be involved on occasions when it is difficult to measure the patient’s QoL due to underlying cognitive impairments and communication deficits [99].
\nSexual desires and the physical capacity to engage in sex continue throughout life. Though many older people enjoy an active sex life, there has been a little mention of sexuality or the problems that older people may face related to sexual issues in government policies [96].
\nThere are several causes for loss of interest and frequency of sexual activity in later life including physical health problems, emotional distress, drug use, male or female sexual dysfunction, practical problems, willingness or lack of partner and not necessarily only ageing [100]. Healthcare professionals routinely avoid discussing sexual problems with older people; however, sharing physical relations and closeness are very important in maintaining long-term emotional and physical intimacy.
\nThorough physical examination from head to toe in a systematic fashion is essential, especially if the cause of acute illness or deterioration is not clear from the history. The clinical signs may not be very obvious as often older people have an atypical presentation, for example, hypothermia instead of hyperthermia, lack of typical signs of heart failure or meningism. Older people sometimes get fatigued after history taking; in such occasions, physical examination may have to be done at a different time.
\nThe investigations should be requested only as indicated by clinical examination. For example, urine analysis should only be done if symptomatic, unexplained systemic sepsis or delirium. As over diagnosis of urinary tract infection may point towards inadequate assessment of frail older people. The common investigations usually include blood oxygen saturation, complete blood count, kidney, liver, bone profile, urinalysis and a chest radiograph. An electrocardiogram should be obtained because there is a higher risk of silent myocardial infarction in older people. Other investigations including CT brain or lumbar puncture are helpful in those with unexplained altered mental status.
\nThe drug and non-drug treatment should be evidence based with aim to treat underlying medical illness. The management of older people needs close liaison work with geriatricians, acute physicians, ED and MDT. The model of care should be established in hospitals so that supportive care for older people can be provided within the first few hours of an admission [101]. For older people with frailty, multiple co-morbidities and an acute illness, admission should be to an Emergency Frailty Unit (EFU), a separate unit within an AMU. EFU or a similar unit led by a geriatrician and the multidisciplinary team (MDT) could not only provide comprehensive person-centred care but also enhance clinical outcomes irrespective of age [102]. In addition, a close working with liaison old-age psychiatry can improve outcome [43]. There should be minimal intra- and inter-hospital transfer to reduce the risk of delirium. Interventions should be planned very carefully and keeping the associated risks in mind, for example, older people should not be routinely catheterised unless there is evidence of urinary retention.
\nHospital admission could be a good opportunity to educate older people and their carers on chronic disease and its management, healthy lifestyles, physical activity, sufficient fluid intake and healthy nutritious foods. Alcohol consumption is under-recognised in older people and an informal discussion by a health professional could be beneficial. A brief discussion with a clinical pharmacist can improve adherence to medication in older people.
\nTraining in hospitals is usually directed towards patient safety, managing acute medical conditions, good handover, and rapid response to a sick patient; however, it is equally essential to augment knowledge and skills of hospital staff in assessing and managing older frail patients. The majority of older patients are admitted to hospital through AMU or directly to EFU, which justifies the need for an EFU geriatrician taking a lead in staff training at the front end [101]. Nursing staff need regular training and education on geriatric giants and frailty [103]. Systematic nurse training has shown to reduce work-related stress [104] and improved outcomes as measured by reduction of inpatient falls [105]. Dementia awareness training should be mandatory and should also be included in induction programmes. Staff members should be encouraged to collect personal information about people with dementia to help improve care, for example, use of ‘This is Me’ document. Information sharing and communication among staff, carers and patients should be improved to ensure that all staff coming into contact with older frail people are aware of their problems and associated needs.
\nOccasionally, problems of older patients are related to neglect or abuse by their caregiver. Hospital staff should consider the possibility of ‘elder abuse’ if there are suggestions on clinical assessment. Certain injury patterns are particularly suggestive, including frequent bruising (middle of the back, upper arms or groin area), fearfulness of a caregiver or unexplained burns.
\nThe regular involvements in audits and analysis of hospital readmission rates, delayed discharge and mortality could identify the needs for service improvement and provision of safe enhanced good quality care for older people.
\nOlder people admitted to hospital are entitled to receive a smooth transition from one stage of hospital care to the next stage of care in the community. A lack of coordinated and person-centred discharge planning can lead to poor outcomes for the patients, thus affecting their health and safety. Poor discharge planning can also lead to inappropriate prolonged LoS or premature discharge and thus result in possible readmission to the hospital.
\nMaintenance of independence and participation in social and voluntary activities are the key benefits of home discharge. This has been quoted as one of the major elements of good QoL. Older people usually have a fear of losing independence as a result of ageing. Older people have reported that being independent, free to please oneself and freedom from time constraints are the best things about growing old [106]. Independence is usually associated with good health, living in own home and ability to walk independently. However, independence is felt to be lost if older people are unable to manage their ADLs. The perceived physical environmental barriers and mobility or ADLs have significant positive correlation [107].
\nThe principal aims of the safe and effective discharge process are to ensure that patients should not stay in the hospital any longer than necessary. Discharge should be on ‘pull system’ rather than on ‘push system’ in order to maximise their social interaction and independence by providing timely and comprehensive carer support according to their needs.
\nDischarge planning should be a systematic coordinated process, which should begin on the first contact with health professional based on the specific needs of the patient with documentation of expected date of discharge (EDD). An older person must be assumed to have capacity unless suggested otherwise and all patients should be encouraged to take their informed decision with an aim to maintain their maximum independence and social interaction in the community.
\nWhere a discharge process is complex, a safe discharge meeting (SDM) should be set and should be attended by members of MDT with SW and preferably by the patient’s relative/carer. There should be a clear purpose of the meeting and needs of the patients should be discussed. The information should be gathered from the SW regarding existing care support services. If there is no need for further specialist referral then discharge date should be set and appropriate requirement of support should be requested by involving social services or voluntary organisations. The confirmation of fitness to discharge must be agreed at least 24 h in advance of EDD with appropriate arrangements for transport.
\nThe patient’s autonomy should be respected both ethically and legally considering that a patient can understand proposed place of discharge, alternatives, risks and benefits in order to consent or refuse it. Patient’s autonomy also requires consulting them and obtaining their informed consent before planning a discharge. The healthcare professionals should practice the principles of beneficence and non-maleficence together and aim at producing net medical benefit with minimal or no harm
\nThe patient’s interests and wishes should be taken into account when considering discharge planning and future care. The hospitalised patients can wax and wane in the level of alertness, so they should be assessed when they are fully awake and have not received any medications, which can impair their cognitive functions. If there are any doubts about the patient’s expressed wishes, they should be evaluated at a later stage. There should be an attempt to involve the family and carers to organise patient-centred hospital discharge process, particularly for those patients who have underlying cognitive or uncorrected sensory impairment.
\nAccording to English Law, an adult has the right to make decisions affecting his or her own life, whether the reasons for that choice are rational, irrational, unknown or even non-existent. Adults over 16 or those who lack capacity to make their own decisions to medical care and treatment are protected by The Mental Capacity Act (MCA) (UK).
\nThe MCA provides a statutory framework and aims to support an individual’s right to protect them from any harm caused due to lack of capacity to make autonomous decisions for themselves [108]. Therefore, every effort should be made to support people who lack capacity to make their own decisions; however, if the person clearly lacks capacity, this should be formally assessed. The decision should be discussed among MDT members and ‘best interest meetings’ should be organised in liaison with family or carers to make important decisions.
\nOlder people discharged should have appropriate access to outpatient follow-up clinics, intermediate and social-care services. There should be effective electronic information-sharing with primary care and community.
\nSome older frail people discharged from hospital could have a poor outcome. Mortality rates for frail older people in the year following discharge from AMUs are high (26% in one series) [109]. Most very old individuals with severe dementia in the community die away from a usual place of residence and hospitals remain the most common place of death [110]. Dementia care during end of life is not similar to the other life-limiting illness [111]. The symptoms experienced by the people with dementia are similar to those with cancer patients but often dementia is not considered as a life-threatening illness. People with dementia not only experience symptoms over longer period but also need more support from the social services and palliative teams [112].
\nTherefore, healthcare and social care professionals should discuss and record advance care planning statements, advance decisions to refuse particular treatments or preferred place of care in future. The decisions made should be shared with community team and families/carers.
\nThe concept of CGA evolved as a result of multiple complex problems in older patients. The first comprehensive meta-analysis of the benefits of CGA was conducted in 1993, which demonstrated that CGA could improve the functional status, survival, reduce the hospital LoS and subsequent health service contacts as well as reduce care-home admissions. This meta-analysis also showed that an improvement in physical function from the geriatric evaluation and management unit (GEMU) interventions was maintained at 12 months (odds ratio (OR): 1.72; 95% confidence interval (CI): 1.06–2.80) [113].
\nAlthough there is a proven role for intensive geriatric rehabilitation in improving the functional outcome and independence in patients with hip fracture [114, 115], other randomised control trials (RCTs) comparing CGA to routine care in later years showed no significance in physical functioning or hospital LoS [116–118].
\nThe systematic review of the literature including 20 randomised controlled trials (RCT) (10, 427 participants) of inpatient CGA for a mixed elderly inpatient population was conducted in 2005. This review confirmed the benefits of inpatient CGA and increased chances of living at home at 1 year, and improved physical and cognitive function with no long-term mortality benefits [119]. More recently, systematic review and meta-analysis involving 17 trials with 4780 people compared the effects of general or orthopaedic geriatric rehabilitation programmes with usual care. The specifically designed inpatient rehabilitation for geriatric patients showed beneficial effects over usual care for functional improvement, preventing admissions to nursing homes and reducing mortality [120].
\nIt appears that setting up a CGA unit carries increased staffing costs or insufficient cost-effective data are available [120] but in American studies of medical and surgical patients the financial costs of managing care for older people in a specialised hospital unit were not more expensive than caring for patients on a usual-care ward [121, 122]. A meta-analysis of RCTs in 2011 has confirmed not only benefits of CGA but also a potential cost reduction compared to general medical care [123]. However, the nature of CGA varies and many, but not all, older people have complex care needs. Therefore, it is difficult to identify which patients will benefit the most and those at risk of adverse outcomes. Frailty status measurement by an index of accumulated deficits generated from routine CGA has shown strong association with adverse outcome; therefore, frailty index may have clinical utility, augmenting clinical judgement in the management of older inpatients [39]. In summary, older frail patients should have early access to inpatient CGA and interdisciplinary involvement in a specialist ward for optimal care to reduce LoS, regain function and physical stability [120].
\nLack of training for doctors, nurses and multidisciplinary members and unfamiliarity with key principles and practices of geriatric medicine [103, 124].
Awareness and support to MDT members is relatively poor.
Lack of interest and associated negative societal attitudes towards older people.
Limited access to dementia care training to meet the complex care needs of older people [125].
Comprehensive geriatric assessment has proven benefit and this should be considered as the evidence-based standard of care for the frail older inpatients. There is a need to configure emergency, acute medical and geriatric services to deliver high-quality CGA for frail older people at the earliest possible time following contact with the acute sector. The aim should be better integration among multidisciplinary members to achieve well-coordinated, high standard of care and improve outcomes. Older people are the major users of acute care and AMU is the key area for initial decision-making; therefore, staff training to meet the needs of frail older people in Acute Medical Unit or Emergency Frailty Unit is mandatory.
\nThe author has no financial or any other kind of personal conflicts with this article.
\nThe author like to thank all members of the Department of Geriatric Medicine, Ysbyty Ystrad Fawr (ABUHB), for their continued support for research activities. The author also like to express his appreciation to Miss Salma Zabaneh, Education Centre/Library, for her support.
\nThe quest for controlled drug release emanating from side effects associated with the application and delivery of conventional drugs has necessitated the need for materials that can transport drugs to target site without difficulty or problem during and after delivery. Normally, drugs are delivered repeatedly on prescription to the body in measures that will bring about remediation and quick recovery to the patient during the treatment period. In this wise, drug concentration levels will increase and when above the body’s tolerance level, the problems associated with over therapeutic concentrations could occur that could result into toxic side [1]. It is also possible that the drug release rate is so fast that therapeutic actions are no longer effective owing to low drug concentrations at the delivery site, which may occur through drug metabolism, degradation, and transport out of the target [1]. Consequently, this phenomenon would result in drug wastage and transport medium loss with high risk offside effects on surrounding body cells, tissues, and organs. The solution to these problems is to have drug carriers that can provide controlled release rate to the target and would allow for complete therapeutic rehabilitation before degradation and transport of excess concentration of drug and carrier medium [2]. The drug and its carrier in form of capsules are orally administered and may be formulated for parenteral administration [3]. The drug release rate of the capsule can be controlled via the use of cellulose coatings exhibiting slow dissolution, incorporation of drug-complexing elements or compounds which hinder fast dissolution of drug, use of compressed tablets, and the inclusion of emulsion and suspensions. Materials that can permit drug release without changing or decaying over time with longer therapeutic windows (days to years) are required. These carries are such that they can be injected and/or implanted directly to target diseased tissues/cells for enhancing delivery efficiency [4]. To achieve target drug delivery, the use of affinity ligands deposited on biomaterial surfaces to allow for a set retention and usage by infirm tissues and cells have been employed [5]. The design of biomaterials for drug carriers aside permitting surface modification using ligands should also shield drugs from speedy break down and/or degeneracy within the target site.
Thus, the design parameters include: (i) the encapsulation of the sufficient drug of the biomaterial for lengthened release pattern to achieve efficient healing, (ii) sustaining drug stability for effective therapeutics through body transport and at the target site while preserving biological activity, (iii) predictable release rate in the therapeutic period from days to years, (iv) biomaterials and its degradation products must be biocompatible and nontoxic within the body, and (v) the cost of biomaterial synthesis and/or fabrication.
Lupron Depot, a poly (lactic-co-glycolic) acid (PLGA) microsphere encapsulating the hormone leuprolide, for the treatment of advanced prostate cancer, and endometriosis [6], PLGA, poly (lactic acid) (PLA), and polyglycolic acid (PGA) materials have FDA approval as micro-particle depot systems as they versatile in controlling material biodegradation time, are biocompatible with nontoxic natural degradation products (lactic acid and glycolic acid). Clinical nanoparticles with FDA approval for cancer nanomedicine treatment of Kaposi’s sarcoma (approved 1995) and for recurrent ovarian cancer (approved 1998) is Doxil [7], a poly (ethylene glycol) (PEG) coated (i.e., PEGylated) liposomal encapsulating the chemotherapeutic doxorubicin [8]. This enhances circulation half-life and tumor uptake of the drug, and also reduces its toxicological activity in patients in comparison to the use of free drug [9]. Other approved nanoparticle drug carriers include Marqibo, a liposomal encapsulating vincristine for rare leukemia treatment [10] and Abraxane an albumin-bound paclitaxel nanoparticle for the treatment of breast cancer [11]; Duragesic-transdermal drug delivery system patch containing the opioid fentanyl embedded within an acrylate polymer matrix, in the treatment of chronic pain [12]; and OROS, an osmotically controlled oral drug delivery technology, incorporated into several oral delivery products including Concerta [13]. Implantable biomaterials used include the Gliadel wafer, which consists of dime-sized wafers comprised of the chemotherapeutic agent carmustine and a polymer matrix made of poly (carboxyphenoxy-propane/sebacic acid), which are surgically inserted into the brain post-tumor resection [14, 15, 16] use as an adjunct to surgery in patients with recurrent glioblastoma multiforme.
An ideal therapeutic drug is expected to treat or cure a disease without resulting to any side effects [17, 18, 19]. However, this goal has not been achieved. Many chemotherapeutics are found to destroy both cancerous and healthy cells within the vicinity of the target site [20]. An efficient chemotherapeutics would administer drug, directly to diseased cell populations. Polymers have been found to permit the creation of “responsive” materials within the host environment and can be formulated with drugs to control release [21]. This polymer attribute is due to tuning propensity of the molecular weight of polymers that can be controlled via monomer stoichiometry using controlled polymerization strategies like ATRP [22], RAFT [23], NMO [24], and ROMP [25]. A bioresponsive material is one that can respond to a specific “trigger” inside or outside of the human body. Because the body have unique pathological parameters as pH gradients, temperatures, enzymes, small molecules, etc., the creation of materials that will respond to physiological alterations in both space and time are required.
Triggers include chemical, biological, and physical stimuli [26, 27], the chemical and biological ones are intrinsic to the body, while the physical stimuli are extrinsic to the body can thus be used to quicken sole drug delivery.
Bioresponsive materials are initiated by redox potential difference tissue environment and its surrounding [28]. There are materials that can respond to both oxidation and reduction triggers, which are incorporated into responsive polymers, e.g., diselenides with chemical structure like those of disulfides [29]. Diselenides allows for alternative triggers within nano-biotechnology applications [30].
The constituents of the human body such as tissues, fluids, and organelles have varied pH values. Areas like stomach, vagina, and lysosomes display acidic pHs (<7); ocular surface (7.1), the blood (≈7.4), and bile (7.8) [21]. Owing to these varied pHs of systems and organs in the body improvement in the efficacy and precision of therapeutic molecules will necessitate the design of polymeric drug delivery systems that are pH specific. pH-responsive materials have been useful in nucleic acid delivery, doxorubicin delivery, and taste masking [31, 32]. The target treatment of tumors has been enhanced using the pH-responsive materials. Such known target delivery includes multifunctional acid sensitive nanocomposites for anticancer drugs and acid-responsive poly(ethylene glycol) derivatives [33] for the controlled release of therapeutics in tumor target treatment (Figure 1).
Schematic illustration of drug loading and controlled release of poly (ethylene glycol) [
Hydrolysis prone materials can be degraded by body fluid via nucleophilic addition of water into an electrophilic functional group on a polymer. The electrophilic functional groups often used on polymers include esters and anhydrides [35]. The Gliadel wafer consisting of chemotherapeutic Carmustine impregnated within a polyanhydride material has been demonstrated as hydrolysis-sensitive materials for drug delivery [36] in the treatment of brain tumors. Enzyme-responsive polymers such as matrix metallo-proteins, hyaluronidases, phospholipases, and prostate-specific antigen [21] have been incorporated into polymers for target drug delivery in areas like tumor imaging, doxorubicin delivery, and minimization of inflammation in the colon [37].
Another drug delivery vehicle is the temperature-sensitive polymers that can operate at both human body temperature of 37°C and at ambient temperature such as 25°C [38]. These polymers include poloxamers, poly(N-alkyl acryl amides), poly(N vinyl caprolactams), cellulose, xyloglucan, and chitosan. These thermo-responsive polymers can be modified via [39] varying the ratio of monomers, end-group modifications, and post-polymerization modifications to make them suitable for varying applications [40].
Magnetic-responsive polymers are therapeutic drug-loaded polymers that work under the influence of magnetic resonance imaging (MRI) to delivery its drug to the target [41]. These include the following: systematic release of dopamine from alginates impregnated with magnetic beads; targeted plasmid delivery to the lung via chitosan nanoparticles; and insulin delivery [42].
Light-responsive polymers are used as external drug delivery systems that use noninvasive and painless techniques [26, 43, 44, 45, 46, 47, 48] as drugs are delivered by light UV- and visible-wavelength irradiation stimulation. In this technique, a remote-activated approach without direct patient contact is used [49]; this includes the release of drugs from a light-responsive azobenzene modified amphiphilic block copolymer to target melanoma cells [50].
There are polymers that can swell or shrink in response to external stimuli [51]. This phenomenon can have stemmed from changes in porosity occasioned as ionic cross-linking molecules are leached, resulting in alteration of the diffusion pathways for sensing molecules. Alginate is a commonly employed polymer that is isolated from seaweed, is relatively biocompatible, and has been used for sustained delivery of vascular endothelial growth factor (VEGF) to a target within the body.
While a limited number of affinity-based delivery systems have been developed for the delivery of neurotrophic factors, we also examine the broad spectrum of reservoir-based delivery systems, including microspheres, electrospun nanofibers, hydrogels, and combinations of these systems.
Drug delivery systems transport biological active agents, such as growth factors and genetic material, into the desired location to promote beneficial effects for the treatment of diseases and disorders [52], osmotic pumps for the delivery of neurotrophic factors [53] to target site, affinity-based delivery systems (ABDS) in which drug loading and controlled release are achieved through the interactions of therapeutic drug and the delivery system, and reservoir-based delivery systems, where a polymer structure encapsulates the drug while its release is controlled via the material properties.
ABDS operate through the noncovalent interactions between device material and target drug [54] in a similar pattern to the interactions that occur in the extracellular matrix where the delivery of proteins and other biomolecules are controlled [55]. ABDS include molecular imprinting, cyclodextrin-based delivery, and heparin-based delivery [56]. Molecular imprinting uses polymer networks synthesized via a precursor molecule that is removed to reveal an imprint that acts as an affinity binding zone. In cyclodextrin-based delivery systems, small hydrophobic drugs are attracted to the hydrophobic center of an oligosaccharide cyclodextrin torus, which permits the complexes formation with enhanced solubility when compared to the drug itself. ABDS is observed to be superior to traditional reservoir-based systems as the release characteristics are dependent on the activities occurring between the drug and the matrix in a way not affected by the matrix properties [57].
Reservoir-based delivery systems (RBDS) are porous with drug release rate controlled by diffusion [58]. In RBDS, the drug is immersed or dissolved in a polymer solvent/reservoir. The drug penetrates via the biodegradable polymer structure to control the initial release followed by another release as surface and bulk erosion occurs in polymer reservoir. RBDS include nanogels, nanoparticles, micelles, hydrogels, microspheres, and electrospun nanofibers.
Microspheres are usually used as controlled drug release systems for stereotactic injections to isolated disease or injury sites in medicine and pharmacology [59]. Drugs like neurotransmitters, hormones, and neurotrophic factors have been encapsulated using microspheres obtained from biodegradable polymers [60]. These polymers include poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and poly(ε-caprolactone) (PCL). Microsphere-based drug delivery uses localized surgical injection to circumvent the blood-brain barrier; this is better in performance to orthodox methods like intravenous injection and oral drug delivery. The parameters of the microsphere such as the particle size, polymer degradation rate, and method of erosion (bulk versus surface degradation) can be utilized to control the rate of drug delivery rates [61]. PCL has been found useful as a microsphere for the carrier of sustained long period drug delivery as it demonstrates the slowest degradation rate [62]. The double emulsion method is often used in synthesizing of microspheres. The method involves dissolving the desired polymer in a nonpolar solvent to form an oil emulsion. The hydrophilic compound that is to be encapsulated is dissolved in an aqueous solution and then emulsified with the dissolved polymer-solvent solution to give a water-in-oil emulsion. After this the solvent evaporates, the polymer solidifies as it forms microspheres that encapsulated the inner aqueous solution [63].
Electrospinning process involves the application of an electric potential to draw out thin nanometer to micrometer diameter polymer fibers (natural or synthetic). A viscous solution of the polymer is prepared (at room or elevated temperature), then pumped via a spinneret nozzle (positive terminal) into an electric field such that the applied force due to the high voltage counters the surface tension leading to the formation of fiber droplets onto a collector plate that serves as negative terminal. The nanofibers produced are often used as drug based-reservoir delivery systems as the pores in the matrix serves as receptive sites for bioactive agents [64]. This fiber production process advantages include surface flexibility with respect to function or application, reduced initial burst release, and the possibility of producing different fiber configuration depending on usage [65]. Drugs are embedded in the pores of electrospun nanofibers by emulsion electrospinning; the target drug is dissolved in a desired polymer solution [64] such as in diclofenac sodium (DS) and human serum albumin (HSA) [66]. Electrospun nanofibers show some draw backs that include formation of drug aggregates during encapsulation along nonsmooth fibers, maintaining uniform fiber size distribution, the use of toxic solvents to form polymer-drug emulsion in drug delivery and its attendant health concerns. Despite these drawbacks, advances in the development of less toxic electrospun fibers, which contain extracellular matrix components such as keratin and collagen, have been developed for wound healing application. The biocompatibility potential of PVA with the bioactive nature of keratin, CoQ10, and antimicrobial mupirocin has been evaluated for wound care due to its ability to support the growth of keratinocytes and hasten skin regeneration [67].
Hydrogel is a hydrophilic network of cross-linked polymer chains with swelling capability but does not dissolve in aqueous solution in the presence of water to create a three-dimensional gel-like structure. The synthesis of hydrogels is through polymerization [68], its properties, and drug release mechanism that depend on the polymer type used. The mechanisms involved in the drug delivery of hydrogel may be diffusion controlled, chemical controlled, swelling controlled, and modulated release systems. The use of acetyl-(Arg-Ala-Asp-Ala)4-CONH2 self-assembling peptide hydrogel to carry model factors such as lysozyme, trypsin inhibitor, BSA, and IgG [69] reveals the potential of these hydrogels carriers of therapeutic agents with the preservation of protein activity. An agarose hydrogel has been found capable of delivering sustained bioactive lysozyme release [70] and was used for the local delivery of BDNF in adult rat models.
The biomaterial surface chemistry and topography impact protein adsorption, cell interaction, and host site response. Monocyte adhesion in vitro [71] have been shown to be altered by its surface chemistry, while in vivo surface chemistry does not significantly influence the foreign body reaction. Polymeric, ceramic, or metallic-based biomaterials exhibit variability in surface properties such as hydrophilic to hydrophobic; hard to soft in vivo [72].
Cell adhesion to adsorbed proteins is achieved via integrin and other receptors in the cell membrane and the occurrence of this triggered intracellular signaling events. Thus, the control of protein adsorption on biomaterials surfaces is crucial to controlling and directing cell responses. Oligopeptides with specific binding sites have been incorporated to control cell adsorption to the protein surface and these include short oligopeptide, e.g., adhesive oligopeptide is an arginine-glycine-aspartic acid (or RGD) [73] that is found in a number of different extracellular matrix proteins, such as fibronectin [74], laminin [75], collagen [76], and vitronectin [77]. Short oligopeptides are less expensive, easy to synthesize, and has greater flexibility for surface modification compared to bulky and labile intact proteins. To a surface modified using nonfouling PEG (99%) and RGD (1%), the protein adsorption was minimal (2 ng/cm2) leaving the sufficient RGD sites for fibroblast cell adhesion [78]. Structure and conformation of oligopeptides influence modulating cell adhesion as demonstrated with the use of immobilized cyclic RGD peptide which increased human bone marrow stromal cell adhesion to that of linear RGD peptides [79] (Table 1).
S/No. | Drug delivery systems | Biomaterial | API | Significance of the study | Reference |
---|---|---|---|---|---|
ORAL DRUG DELIVERY SYSTEMS | |||||
Silk Nanoparticles | Silk and fibrin | Celecoxib and curcumin | Silk fibroin nanoparticles were seen to promote anti-inflammatory properties of celecoxib or curcumin and could be exploited for oral osteoarthritis management since a controlled drug release was achieved by varying the drug loading | [80] | |
Electrospun fibers | Polylactic acid | Metronidazole | PLA nanofibers associated with metronidazole (MNZ) were used to control microbiological proliferation during periodontitis treatment, inhibiting bacteria growth during the treatment | [81] | |
OCULAR DRUG DELIVERY SYSTEMS | |||||
Nanocomposite hydrogel | Hyaluronic acid | Latanoprost | The hyaluronic acid nanocomposite hydrogels, with controlled degradation properties and sustained release, could serve as potential drug delivery systems for many ocular diseases as they controlled the release of latanoprost in vitro | [82] | |
Hydrogel contact lens | Silicone | Ofloxacin and Chloramphenicol | The drug release from the lenses was directly proportional to the amount of drug loaded and the lenses at the different loading concentrations showed transmittance of 95–97%. The silicone hydrogel contact lenses can be used to control drug delivery to the eye and is an alternative ocular delivery technique in the treatment or prevention of corneal infections | [83] | |
PULMONARY DRUG DELIVERY SYSTEMS | |||||
Porous particles | Poly(lactide-co-glycolide) (PLGA) | Celecoxib | Large porous celecoxib-PLGA microparticles prepared using supercritical fluid technology exhibited sustained drug delivery and antitumor efficacy, without causing any significant toxicity | [84] | |
Nanoparticles | Nanopolymeric particles consisting of hydroxyl propyl methylcellulose (HPMC), poly-vinylpyrrolidone (PVP) | Fluticasone | The in vitro antibacterial studies showed that HPMC-PVP-FLU nanoparticles displayed superior effect against Gram-positive bacteria compared to the unprocessed FLU and positive control | [85] | |
IV | IMPLANT DRUG DELIVERY SYSTEMS | ||||
Silk disc implants | Silk fibrin | IgG antibody or human immunodeficiency virus (HIV) inhibitor 5P12-RANTES | SF was formulated into insertable discs that can encapsulate either IgG antibody or human immunodeficiency virus (HIV) inhibitor 5P12-RANTES. The water vapor annealing showed a sustained release for 31 days and this released protein could inhibit HIV infection in both blood and human colorectal tissue | [86] | |
Bone biomaterials implant | Hydroxyapatite | Doxorubicin-loaded cyclodextrin | Hydroxyapatite-cyclodextrin-doxorubicin chemotherapeutic strategy enhanced the drug-targeting effect on tumor cells while protecting the more sensitive healthy cells after implantation. A successful integration of such a drug delivery system might allow healthy cells to initially survive during the doxorubicin exposure period | [87] | |
V | SYSTEMIC DRUG DELIVERY | ||||
Polylactide scaffold hydrogel injections | Cholesterol-modified poly(ethylene glycol)–polylactide | Chondrocytes | The formulation shows lower critical gelation temperature, higher mechanical strength, larger pore size, better chondrocyte adhesion, and slower degradation compared to plain polylactide scaffold gels. The hydrogel serves as a promising chondrocyte carrier for cartilage tissue engineering and gives an alternative solution to surgical cartilage repair | [88] | |
ANG-(1–7) functionalized plant chloroplast | Lyophilized lettuce cells (ACE2/ANG-(1–7)) | Lyophilized lettuce cells (ACE2/ANG-(1–7)) | Toxicology studies showed that both male and female rats tolerated ~10-fold ACE2/ANG-(1–7) higher than efficacy dose. The efficient attenuation of pulmonary arterial hypertension with no toxicity augurs well for the clinical advancement of the first oral protein therapy to prevent/treat underlying pathology for this disease. | [89] | |
VI | VAGINAL DRUG DELIVERY SYSTEMS | ||||
Organogel | Palm oil and hyaluronic acid | Maraviroc | There was a 2.5-fold increase in the percentage of maraviroc release in the presence of hyaluronidase, hence the effectiveness of hyaluronidase enzyme acting as a trigger. This shows the potential use of palm oil/hyaluronic acid-based organogel for the vaginal delivery of anti-HIV microbicide for HIV prevention | [90] | |
Vaginal rings | Silicone matrix polymer | Dapivirine | A monthly vaginal ring containing dapivirine reduced the risk of HIV-1 infection among African women, with increased efficacy in subgroups with evidence of increased adherence | [91] | |
VII | TOPICAL DRUG DELIVERY SYSTEMS | ||||
Electrospun fibers | Polylactic acid and collagen | Collagen and silver sulfadiazine | The electrospun fibers were nontoxic to the cells and provided favorable substrates for the neonatal epidermal keratinocytes cells to undergo cell attachment and proliferation, hence its potential for use in chronic wound management | [92] | |
Hydrogel | Polyvinyl alcohol and carbopol | Diclofenac diethylamine | In vitro skin permeation for 10 h showed that the enhancement ratios of the flux of diclofenac was higher compared to the marketed formulations. The study highlighted the advantage of the experimental transdermal hydrogel over the hydrogel with microsized drug particles | [93] |
Drug delivery systems showing the significance of the biomaterials utilized in delivering active pharmaceutical ingredients at their biological target site.
Poly (ethylene glycol) (PEG), or poly(ethylene oxide) (PEO) having nonfouling surfaces demonstrates protein and cell resistance capabilities. PEG have been attached to materials in such a manner to render them nonfouling through processes like covalent immobilization, adsorption, or interpenetration. PEG has been covalently attached to mussel adhesive protein to form a nonfouling and a sticky segment copolymer [94] with gold and titanium surfaces attached to the sticky segment, while the PEG chains occur at the new interface. It should be noted that the nonfouling ability/attribute of PEG is dependent on the surface chain density that is prone to oxidants damaged. However, the use of plasma deposition of tetra ethylene glycol dimethyl ether (tetraglyme) on PEG will reduce protein surface adsorption [95]. Other materials with nonfouling surfaces include phospholipid surfaces [96] and saccharide surfaces [97], and these biomaterials ensure increased compatibility issues between the drug carrier systems and biological systems to which they are introduced to elicit a pharmacological activity.
Materials which respond to environmental changes are attractive particularly in vivo as these can be utilized to control drug release, cell adhesiveness, mechanical properties, or permeability. These environmental changes can be brought about by stimulants like pH [98], temperature [99], and light [100]. The body employs changes in pH to facilitate a range of different processes. For example, along the gastrointestinal track, food is broken down into nutritive substances in the stomach under acidic pH ∼ 2 and subsequently absorbed in the small intestine (pH ∼ 7). Patient often prefers the oral drug delivery requiring routine, periodic delivery of drugs and for effectiveness, the drug must resist the stomach acidic pH. The pH-sensitive materials that are mindful of gastrointestinal tract pH variation have been developed to transport drugs successfully through the stomach to the small intestine. Such successful materials include pH responsive hydrogels prepared from poly(methacrylic acid) grafted with poly(ethylene glycol) (PMAA-g-PEG) that swells in response to pH. For instance, the gel shrinks by trapping the drug cargo pH ∼ 2 as interpolymer complexes are formed, but at physiological pH ∼ 7, the gel can swell 3–25 times based on its composition as it releases its cargo in the target site [101]. Insulin-loaded PMAA-g-PEG gels have been orally delivered to diabetic mice with a significant decrease in glucose levels as protein function is protected in acidic and digestive enzymes environments [102].
Self-organization or self-assembly is based on the formation of weak noncovalent bonds, like hydrogen, ionic, or Van der Waals bonds or hydrophobic interactions [103]. In amphiphilic molecules, there are hydrophobic and hydrophilic segments that self-assemble to form nanometer 3D structures like micelles, vesicles, and tubules, which depend on the molecule’s length and composition [104, 105, 106, 107]. When any of these are dispersed in aqueous solvent, the hydrophobic segments agglomerate and water is expelled to produce a well-ordered structure useful in biomedical applications. Phospholipid a naturally occurring amphiphilic molecule that is largely compose of cell membrane is one such amphiphilic molecules while an oligomer, a polymer of amino acids, can be synthesized to have hydrophobic, hydrophilic, charged, etc., regions that can self-assemble into a macroscopic hydrogel [108]. The self-assembled biomaterials can be engineered for use in nanotechnology, tissue engineering for drug and cell carriers.
Polymers are large molecules formed from simple monomers and may be synthetic or biopolymers that are the constituents of living organisms like proteins, nucleic acids, and sugars. Biopolymers are active in controlling and regulating many biochemical and biophysical functions of living cells, and thus can participate in cooperative interactions, resulting in nonlinear response to external stimuli. The cooperative interaction mechanism of biopolymers is utilized in producing synthetic polymers that are similar in behavior to biopolymers, which are used as biomaterials with ability to interface with biological systems for a variety of living cells functions.
Polymeric, biodegradable materials are often useful in biomedical applications, as the polymers degrade into normal metabolites of the body or eliminated from the body with or without further metabolic transformation [109, 110]. Developed polymeric biomaterials have physical and chemical properties that are maintained and are not tampered with during synthesis. The use of synthetic polymeric biomaterials includes artificial corneal substitute, blood contacting devices, hip joint replacements, and formation of intraocular lenses [111, 112]. Biodegradable polymers are either natural or synthetic. Natural polymers are derived from natural resources and have potential to be considered for biomedical and pharmaceutical applications owing to biocompatibility, biomimicking environments, unique mechanical properties, and biodegradability. Natural polymers are prone to viral infection, antigenicity, and unstable material supply, which limit biomedical application. On the other hand, synthetic polymers are flexible in synthesis procedure technique with excellent reproducibility which made them useful for surgical and short-term medical application, orthopedic applications that may slowly transfer the load as it degrades [113].
The drug administration into the body is either via an oral or intravenous route with repeated administration done to increase concentration and performance. But this may reach an extreme level before it declines rapidly especially when the elimination rate from the body is high. A too low or too high drug concentration in the body will not benefit the patient because of the side effects. This phenomenon then becomes a concern requiring the use of controlled drug release mechanism which can only be offered by biomaterials [114]. For controlled drug release, the therapeutic and bioactive agents are enveloped or encapsulated in an insoluble biodegradable subnano, nano, micropolymer matrix cavity where the therapeutic agents are released in a controlled fashion.
Widely used drug delivery systems include a liposomal drug delivery system [115, 116] that consists of phospholipids, i.e., fatty acid esters and fat alcohol ethers of glycerol phosphatides; they are negatively charged at physiological pH due to their phosphate groups. Cationic liposomes are prepared using lipid molecules having a quaternary ammonium head group. Because cellular membranes carry negative charges, cationic liposomes interact with these cellular membranes [117]. The stability of liposomes in biological environment is improved with steric stability that can extend its blood circulation time after being administered [118]. Biodegradable polymers are usually used to enhance the steric stability of the liposomes. Natural biodegradable polymers that are suitable for drug delivery systems include proteins (collagen, gelatin, albumin, etc.) and polysaccharides (starch, dextran, chitosan, etc.) [119].
Polysaccharides are many monosaccharide repeating units with high molecular weight. It is biodegradable, biocompatible, and water soluble which make suitable for drug delivery. There are several different types of polysaccharides having different functional groups, which are as follows:
Alginic acid is a linear hetero polysaccharide, nonbranched, high-molecular-weight binary copolymer of (1–4) glycosidic linkage with β-D-mannuronic acid and α-L guluronic acid monomers [120, 121]. Natural alginic acid can be obtained from the cell walls of brown algae. Its acidic nature helps in its spontaneous formation of salts and later gels in the presence of divalent cations like calcium ions. This occurs by the interaction of divalent cations with guluronic acid blocks present on other polysaccharide chains. The gel property paves way for the encapsulation of molecules that can act as drugs within alginate gels with negligible side effects. The drug delivery mechanism of alginates is hinged on the drug polymer interaction and chemical immobilization of the drug on the polymer backbone via reactive carboxylate groups [122, 123, 124].
Starch, which is a carbohydrate source can be isolated from corn, wheat, potato, tapioca, rice, etc., and consists of two glucosidic macromolecules: 20–30% of linear molecule—amylase and 70–80% of branched molecule—amylopectin. The products of starch processing include thin films, fibers, and porous matrices. It is an important polymer for thermoplastic biodegradable materials due to its low cost, availability, biocompatibility, biodegradability, and having renewable resources [125]. The products of starch degradation include fructose and maltose that are low molecular weight sugar [126]. Microspheres from starch have bioadhesive drug delivery system potential for nasal delivery of proteins [127].
Dextran is a natural polysaccharide of large glucose molecules with long and branched chains of varying lengths from 3 to 2000 Kd at 1,6- and partly at 1,3-glucosidic linkages. It is synthesized from sucrose via lactic-acid bacteria like
Pullulan occurs naturally as linear homopolysaccharide polymer with maltotriose units of 3-glucose or D-glucopyranose units which are linked by α-(1 → 4) glycosidic linkages. It is edible, bland, and tasteless and thus is added to food and beverages. It serves as a coating agent in pharmaceutics, breath fresheners, or oral hygiene products [130]. Consecutive maltotriose units are linked to one another via α-(1 → 6) glycosidic bond. The pullulan backbone structure is similar to dextran, as both are plasma expanders. Pullulan is commercially synthesized via fermentation process involving the growth of fungus
Hyaluronic acid also a natural occurring negatively charged linear polysaccharide made of repeating disaccharide units of D-glucuronic acid and 2-acetamido-2-deoxy-D-glucose monosaccharide units. It exists majorly in articular cartilage, connective tissues, synovial fluids of mammals and the mesenchyme of developing embryos. It is water soluble and forms highly viscous solutions and therefore suitable for use as wound dresser as it can act as scavenger for free radicals in wound sites to modulate inflammation [131]. Its use in tissue repair application include to protect delicate tissue in the eye in removal of cataract, corneal transplantation, and glaucoma surgery, as vitreous substitute in retina re-attachment surgery, to relieve pain and improve joint mobility in osteoarthritis (knee) patients suffering and accelerate bone fracture healing [132].
Chitin a natural occurring polysaccharide of 1 → 4 β-linked glycan containing 2-acetamido-2-deoxy-D-glucose is a component of shells of crustaceans, cell walls of fungi, etc. When chitin is deacetylated chitosan a semi-crystalline linear copolymer polysaccharide is produced with (1 → 4) β-linked D-glucosamine and some N-acetyl glucosamine groups. The degree of deacetylation (DD) of chitosan may be from 70% and 90% and the MW is in between 10 and 1000 k [133]. While chitin is insoluble in regular solvents, chitosan is fully soluble in aqueous solutions with pH <5.0 [134]. Chitosan degrades in vivo enzymatically via lysozyme to nontoxic products [134]. Chitosan is easy to process and applied, oxygen permeability, water absorptivity, hemostatic property, and ability to induce interleukin-8 from fibroblasts. It uses include wound and burn dressing material, drug delivery and controlled drug release.
Polyurethane is a polymer with a chain of organic units linked by carbamate (urethane), which is formed from two or several bi- or higher-functional monomers, one having two or more isocyanate functional groups (–N=C=O) and the other with two or more hydroxyl groups (–OH) [135]. It is a material with similar elasticity to rubber, possess toughness and durability comparable to metal, and is chemically inert. Polyurethane micelles are suitable drug delivery systems.
Advances in medical research have led to the exploration of various materials as drug carriers for suitable delivery. Biomaterials are currently well explored in recent years as a result of their ubiquitous nature, ease of accessibility, biodegradability, and biocompatibility with living tissues. They have been singly used or blended with other materials as composites. This chapter has thus discussed the different biomaterials with their functionalities in the area of drug release. More biomaterials can be explored by processing and characterizations from natural origin to ensure effective performance and limit health complications associated with drug release.
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In-service vehicles equipped with sensors and GPS systems can act as probes to detect and analyse real-time vehicle vibration. Recently, a compact on-board sensing device has been developed. This chapter describes the track condition monitoring system that uses a compact on-board sensing device and diagnosis software. The diagnosis software provides the function of detecting track faults using the root mean square (RMS) of the car-body acceleration. It also allows analysis in the time-frequency domain using wavelet transform. A monitoring experiment in a local railway line showed that the system is effective for practical application.",book:{id:"4789",slug:"railway-research-selected-topics-on-development-safety-and-technology",title:"Railway Research",fullTitle:"Railway Research - Selected Topics on Development, Safety and Technology"},signatures:"Hitoshi Tsunashima, Hirotaka Mori, Masayuki Ogino and Akira\nAsano",authors:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",slug:"hitoshi-tsunashima",fullName:"Hitoshi Tsunashima"}]},{id:"59302",doi:"10.5772/intechopen.74277",title:"Model-Based Fault Analysis for Railway Traction Systems",slug:"model-based-fault-analysis-for-railway-traction-systems",totalDownloads:1386,totalCrossrefCites:1,totalDimensionsCites:5,abstract:"Fault analysis in industrial equipment has been usually performed using classical techniques such as failure modes and effects analysis (FMEA) and fault tree analysis (FTA). Model-based fault analysis has been used during the last several years in order to overcome the limitations of classical methods when complex industrial equipment has to be analyzed. In railway and automotive sectors, the development and validation of new products are based on hardware-in-the-loop (HIL) platforms. In this chapter, a methodology to enhance classical FMEAs is presented. Based on HIL simulations, the objective is to improve the results of the fault analysis with quantitative information about the effects of each fault mode. In this way, the impact of the fault analysis in the design of the traction system, the development of new diagnostic functionalities and in the maintenance tasks will increase.",book:{id:"6065",slug:"modern-railway-engineering",title:"Modern Railway Engineering",fullTitle:"Modern Railway Engineering"},signatures:"Jon del Olmo, Fernando Garramiola, Javier Poza and Gaizka\nAlmandoz",authors:[{id:"149511",title:"Dr.",name:"Gaizka",middleName:null,surname:"Almandoz",slug:"gaizka-almandoz",fullName:"Gaizka Almandoz"},{id:"149644",title:"Dr.",name:"Javier",middleName:null,surname:"Poza",slug:"javier-poza",fullName:"Javier Poza"},{id:"235660",title:"Dr.",name:"Jon",middleName:null,surname:"Del Olmo",slug:"jon-del-olmo",fullName:"Jon Del Olmo"},{id:"241062",title:"Mr.",name:"Fernando",middleName:null,surname:"Garramiola",slug:"fernando-garramiola",fullName:"Fernando Garramiola"}]},{id:"49375",doi:"10.5772/61517",title:"Experimental and Simulation Study of the Superstructure and Its Components",slug:"experimental-and-simulation-study-of-the-superstructure-and-its-components",totalDownloads:2559,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"The issues discussed in this chapter are of interest of both the manufacturers and the experts responsible for condition of the track superstructure. In general, stress in steel elements may affect the energy state, phase changes, and corrosion. It may reduce fatigue strength and cause damage and cracks of the rails. It is one of the causes of accelerated development of standard railhead defects. Proper selection of, e.g., bending process parameters provides uniform distribution and acceptable level of residual stresses in the bent components. Residual stresses that develop during manufacturing process in the railway turnout steel components can change their strength properties. The first part of this chapter presents ultrasonic measurement method and computer simulation that allowed to develop a method to diagnose state and distribution of residual stresses in steel components of the railway turnout (wing rails and switch blades) in the production process. The second part of this chapter includes experimental and simulation studies of superstructure in operational conditions. A track substructure with a crashed stone composite is a solution of reinforced standard track substructure. The results are used to draw conclusions concerning further development and possible modifications of a proposed solution. A significant number of simulation calculations also allow to determine the duration of guaranteed functionality of a reinforced track substructure.",book:{id:"4789",slug:"railway-research-selected-topics-on-development-safety-and-technology",title:"Railway Research",fullTitle:"Railway Research - Selected Topics on Development, Safety and Technology"},signatures:"Jacek Kukulski",authors:[{id:"175842",title:"Ph.D.",name:"Jacek",middleName:null,surname:"Kukulski",slug:"jacek-kukulski",fullName:"Jacek Kukulski"}]},{id:"49716",doi:"10.5772/62080",title:"A Systems View of Railway Safety and Security",slug:"a-systems-view-of-railway-safety-and-security",totalDownloads:4114,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"This chapter approaches the concerns over safety and security of modern mainline and light railways from a systems perspective. It addresses the two key concerns from the view point of systemic emergence arising from the interaction between all the principal constituents of the railway system, namely infrastructure, rolling stock, energy and human element comprising workers, passengers and the neighbours of the railways.",book:{id:"4789",slug:"railway-research-selected-topics-on-development-safety-and-technology",title:"Railway Research",fullTitle:"Railway Research - Selected Topics on Development, Safety and Technology"},signatures:"Ali G. Hessami",authors:[{id:"108303",title:"Prof.",name:"Ali G.",middleName:null,surname:"Hessami",slug:"ali-g.-hessami",fullName:"Ali G. Hessami"}]},{id:"57840",doi:"10.5772/intechopen.71768",title:"Advanced Train Positioning/Communication System",slug:"advanced-train-positioning-communication-system",totalDownloads:1665,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"In the past, in order to ensure train positioning as well as ground-to-train information exchange, railways have adopted various technologies. Over time, each new generation of equipment enriched the global information exchange but, as a consequence, necessitated higher data rate transfers. For the positioning functionality, the existing localisation systems are still limited, since most of them require an infrastructure installation with constraints such as laying equipment between the rails or having high database maintenance requirements and computational costs. Moreover, some of them accumulate errors (odometers and inertial sensors) or offer limited coverage in shadowed areas (GNSS, etc.). Currently, in railway applications, a widely used localization system is based on proprioceptive sensors embarked in the train. This on-board system is coupled to the use of balises located at ground between the rails. These balises are kilometre markers. They are used to compensate for the drift of the localization information computed using the proprioceptive sensors alone, when the train moves. The balises provide absolute localization information whenever the train passes over them. They can also provide spot communication during the short period of time when trains are passing over them. In the first part of this chapter, techniques for achieving train positioning and data exchanges between trains and infrastructure are introduced. In the second part, a new balise is proposed. Particular attention is paid to the contribution of this new solution in terms of localization error and communication performances.",book:{id:"6065",slug:"modern-railway-engineering",title:"Modern Railway Engineering",fullTitle:"Modern Railway Engineering"},signatures:"Fouzia Elbahhar and Marc Heddebaut",authors:[{id:"140822",title:"Dr.",name:"Fouzia",middleName:null,surname:"Elbahhar",slug:"fouzia-elbahhar",fullName:"Fouzia Elbahhar"}]}],mostDownloadedChaptersLast30Days:[{id:"57056",title:"Transmission-Based Signaling Systems",slug:"transmission-based-signaling-systems",totalDownloads:3049,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"In this chapter, we describe the principal communication systems applied to the transmission-based signaling (TBS) systems for railways. Typical examples are communication-based train control (CBTC), European Rail Traffic Management System (ERTMS), and distance to go (DTG). Moreover, to properly address some of the challenges that need to face these systems, we will provide a deep insight on propagation issues related to all the environments (urban, suburban, rural, tunnel, etc.). We will highlight all the communication-related issues and the operational as well. Finally, a detailed survey on the directions of research on all these topics is provided, in order to properly cover this interesting subject. In this research, hot topics like virtual coupling are explained as well.",book:{id:"6065",slug:"modern-railway-engineering",title:"Modern Railway Engineering",fullTitle:"Modern Railway Engineering"},signatures:"Cesar Briso-Rodríguez, Juan Moreno García-Loygorri and Lei Zhang",authors:[{id:"171013",title:"Dr.",name:"Cesar",middleName:null,surname:"Briso",slug:"cesar-briso",fullName:"Cesar Briso"},{id:"216915",title:"Dr.",name:"Juan",middleName:null,surname:"Moreno Garcia-Loygorri",slug:"juan-moreno-garcia-loygorri",fullName:"Juan Moreno Garcia-Loygorri"},{id:"216916",title:"Dr.",name:"Lei",middleName:null,surname:"Zhang",slug:"lei-zhang",fullName:"Lei Zhang"}]},{id:"49375",title:"Experimental and Simulation Study of the Superstructure and Its Components",slug:"experimental-and-simulation-study-of-the-superstructure-and-its-components",totalDownloads:2553,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"The issues discussed in this chapter are of interest of both the manufacturers and the experts responsible for condition of the track superstructure. In general, stress in steel elements may affect the energy state, phase changes, and corrosion. It may reduce fatigue strength and cause damage and cracks of the rails. It is one of the causes of accelerated development of standard railhead defects. Proper selection of, e.g., bending process parameters provides uniform distribution and acceptable level of residual stresses in the bent components. Residual stresses that develop during manufacturing process in the railway turnout steel components can change their strength properties. The first part of this chapter presents ultrasonic measurement method and computer simulation that allowed to develop a method to diagnose state and distribution of residual stresses in steel components of the railway turnout (wing rails and switch blades) in the production process. The second part of this chapter includes experimental and simulation studies of superstructure in operational conditions. A track substructure with a crashed stone composite is a solution of reinforced standard track substructure. The results are used to draw conclusions concerning further development and possible modifications of a proposed solution. A significant number of simulation calculations also allow to determine the duration of guaranteed functionality of a reinforced track substructure.",book:{id:"4789",slug:"railway-research-selected-topics-on-development-safety-and-technology",title:"Railway Research",fullTitle:"Railway Research - Selected Topics on Development, Safety and Technology"},signatures:"Jacek Kukulski",authors:[{id:"175842",title:"Ph.D.",name:"Jacek",middleName:null,surname:"Kukulski",slug:"jacek-kukulski",fullName:"Jacek Kukulski"}]},{id:"59304",title:"Improving Feasibility of High-Speed Train Project: Creating Added Value",slug:"improving-feasibility-of-high-speed-train-project-creating-added-value",totalDownloads:1471,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Infrastructure plays a significant role in increasing economic development by providing access of transportation and improving connectivity. High-speed train (HST), one of mega infrastructure projects, has a positive impact on economic development of a nation. However, the project feasibility requires the maximum value for money and an acceptable risk to attract private investors. This study aims to improve the feasibility of the project by producing a conceptual design of Jakarta-Surabaya high-speed train in Indonesia. Value engineering will be used to evaluate both technical and financial aspects of the project. The methodology uses both qualitative and quantitative approaches through a case study, in-depth interviews, and life-cycle cost analysis. The result shows an optimum route sketching for the project and potential added value to the project. It consists of the solar cell, fiber optic, tourism, and transit-oriented development. The output also generates the division of responsibility between the government and business entity during the project lifecycle regarding the project financing. The institutional scheme will regulate the position and roles for each related stakeholder that was involved in the HST project development.",book:{id:"6065",slug:"modern-railway-engineering",title:"Modern Railway Engineering",fullTitle:"Modern Railway Engineering"},signatures:"Mohammed Ali Berawi",authors:[{id:"207251",title:"Dr.",name:"Mohammed Ali",middleName:null,surname:"Berawi",slug:"mohammed-ali-berawi",fullName:"Mohammed Ali Berawi"}]},{id:"57840",title:"Advanced Train Positioning/Communication System",slug:"advanced-train-positioning-communication-system",totalDownloads:1660,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"In the past, in order to ensure train positioning as well as ground-to-train information exchange, railways have adopted various technologies. Over time, each new generation of equipment enriched the global information exchange but, as a consequence, necessitated higher data rate transfers. For the positioning functionality, the existing localisation systems are still limited, since most of them require an infrastructure installation with constraints such as laying equipment between the rails or having high database maintenance requirements and computational costs. Moreover, some of them accumulate errors (odometers and inertial sensors) or offer limited coverage in shadowed areas (GNSS, etc.). Currently, in railway applications, a widely used localization system is based on proprioceptive sensors embarked in the train. This on-board system is coupled to the use of balises located at ground between the rails. These balises are kilometre markers. They are used to compensate for the drift of the localization information computed using the proprioceptive sensors alone, when the train moves. The balises provide absolute localization information whenever the train passes over them. They can also provide spot communication during the short period of time when trains are passing over them. In the first part of this chapter, techniques for achieving train positioning and data exchanges between trains and infrastructure are introduced. In the second part, a new balise is proposed. Particular attention is paid to the contribution of this new solution in terms of localization error and communication performances.",book:{id:"6065",slug:"modern-railway-engineering",title:"Modern Railway Engineering",fullTitle:"Modern Railway Engineering"},signatures:"Fouzia Elbahhar and Marc Heddebaut",authors:[{id:"140822",title:"Dr.",name:"Fouzia",middleName:null,surname:"Elbahhar",slug:"fouzia-elbahhar",fullName:"Fouzia Elbahhar"}]},{id:"49716",title:"A Systems View of Railway Safety and Security",slug:"a-systems-view-of-railway-safety-and-security",totalDownloads:4110,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"This chapter approaches the concerns over safety and security of modern mainline and light railways from a systems perspective. It addresses the two key concerns from the view point of systemic emergence arising from the interaction between all the principal constituents of the railway system, namely infrastructure, rolling stock, energy and human element comprising workers, passengers and the neighbours of the railways.",book:{id:"4789",slug:"railway-research-selected-topics-on-development-safety-and-technology",title:"Railway Research",fullTitle:"Railway Research - Selected Topics on Development, Safety and Technology"},signatures:"Ali G. Hessami",authors:[{id:"108303",title:"Prof.",name:"Ali G.",middleName:null,surname:"Hessami",slug:"ali-g.-hessami",fullName:"Ali G. 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The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. This Series is intended for researchers and students alike interested in this fascinating field and its many applications.",coverUrl:"https://cdn.intechopen.com/series/covers/14.jpg",latestPublicationDate:"July 5th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"218714",title:"Prof.",name:"Andries",middleName:null,surname:"Engelbrecht",slug:"andries-engelbrecht",fullName:"Andries Engelbrecht",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNR8QAO/Profile_Picture_1622640468300",biography:"Andries Engelbrecht received the Masters and PhD degrees in Computer Science from the University of Stellenbosch, South Africa, in 1994 and 1999 respectively. He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). 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He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. He is a Senior Member of the IEEE Computer, the IEEE Computational Intelligence, and the IEEE Systems, Man, and Cybernetics Societies, and the Association of Computing Machinery (ACM). Finally, his main research interests include data science, computational intelligence, and their applications.",institutionString:null,institution:{name:"University of Córdoba",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"26",title:"Machine Learning and Data Mining",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",isOpenForSubmission:!0,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. His research interests include intelligent and embedded systems.",institutionString:"Universidad Autonoma de Queretaro",institution:{name:"Autonomous University of Queretaro",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null},{id:"27",title:"Multi-Agent Systems",coverUrl:"https://cdn.intechopen.com/series_topics/covers/27.jpg",isOpenForSubmission:!0,editor:{id:"148497",title:"Dr.",name:"Mehmet",middleName:"Emin",surname:"Aydin",slug:"mehmet-aydin",fullName:"Mehmet Aydin",profilePictureURL:"https://mts.intechopen.com/storage/users/148497/images/system/148497.jpg",biography:"Dr. Mehmet Emin Aydin is a Senior Lecturer with the Department of Computer Science and Creative Technology, the University of the West of England, Bristol, UK. His research interests include swarm intelligence, parallel and distributed metaheuristics, machine learning, intelligent agents and multi-agent systems, resource planning, scheduling and optimization, combinatorial optimization. Dr. Aydin is currently a Fellow of Higher Education Academy, UK, a member of EPSRC College, a senior member of IEEE and a senior member of ACM. In addition to being a member of advisory committees of many international conferences, he is an Editorial Board Member of various peer-reviewed international journals. He has served as guest editor for a number of special issues of peer-reviewed international journals.",institutionString:null,institution:{name:"University of the West of England",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:20,paginationItems:[{id:"82526",title:"Deep Multiagent Reinforcement Learning Methods Addressing the Scalability Challenge",doi:"10.5772/intechopen.105627",signatures:"Theocharis Kravaris and George A. 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He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:null},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",country:{name:"Romania"}}},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"357085",title:"Mr.",name:"P. Mohan",middleName:null,surname:"Anand",slug:"p.-mohan-anand",fullName:"P. Mohan Anand",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356696",title:"Ph.D. Student",name:"P.V.",middleName:null,surname:"Sai Charan",slug:"p.v.-sai-charan",fullName:"P.V. Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356823",title:"MSc.",name:"Seonghee",middleName:null,surname:"Min",slug:"seonghee-min",fullName:"Seonghee Min",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Daegu University",country:{name:"Korea, South"}}},{id:"353307",title:"Prof.",name:"Yoosoo",middleName:null,surname:"Oh",slug:"yoosoo-oh",fullName:"Yoosoo Oh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:"Yoosoo Oh received his Bachelor's degree in the Department of Electronics and Engineering from Kyungpook National University in 2002. He obtained his Master’s degree in the Department of Information and Communications from Gwangju Institute of Science and Technology (GIST) in 2003. In 2010, he received his Ph.D. degree in the School of Information and Mechatronics from GIST. In the meantime, he was an executed team leader at Culture Technology Institute, GIST, 2010-2012. In 2011, he worked at Lancaster University, the UK as a visiting scholar. In September 2012, he joined Daegu University, where he is currently an associate professor in the School of ICT Conver, Daegu University. Also, he served as the Board of Directors of KSIIS since 2019, and HCI Korea since 2016. From 2017~2019, he worked as a center director of the Mixed Reality Convergence Research Center at Daegu University. From 2015-2017, He worked as a director in the Enterprise Supporting Office of LINC Project Group, Daegu University. 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The research resented can consist of primary studies on various animal biology fields such as genetics, nutrition, behavior, welfare, and animal production, to name a few. 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Dr. Şentürk serves as the editorial board member of several international journals.",institutionString:"Ağrı İbrahim Çeçen University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Ağrı İbrahim Çeçen University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"July 5th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:320,numberOfPublishedBooks:32,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",fullName:"Abdulsamed Kükürt",profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",institutionString:null,institution:{name:"Kafkas University",institutionURL:null,country:{name:"Turkey"}}},{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"chapter.detail",path:"/chapters/51670",hash:"",query:{},params:{id:"51670"},fullPath:"/chapters/51670",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()