\r\n\t \r\n\tThe aims of this book are to present the updates and advances in the field of resuscitation including AHA guidelines, latest evidence for the airway protection equipment, the role of AED in cardiac arrest, latest advances and the evidence including ongoing updated research including return of spontaneous circulation and post resuscitation care and support including neurological and hemodynamic stability. \r\n\t \r\n\tThe content of this book will be focused on latest research in the field which will create a concise updated information for medical, nursing and paramedical personnel. Furthermore, the book will also touch upon controversial topics in resuscitation and will try to bring out latest evidence intending to solve the controversies in the field of resuscitation. This book will be an excellent extract of all available updates and ongoing research for a complete knowledge of resuscitation.
",isbn:null,printIsbn:"979-953-307-X-X",pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"4e1d9c7965a911a1d2c3c1337a16acc5",bookSignature:"Dr. Mayank Gyan Vats",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/8226.jpg",keywords:"CPR, Airway, Intubation, AED, BLS, ACLS, Cardiac Arrest, Arrhythmia, Advances",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 30th 2019",dateEndSecondStepPublish:"November 20th 2019",dateEndThirdStepPublish:"January 19th 2020",dateEndFourthStepPublish:"April 8th 2020",dateEndFifthStepPublish:"June 7th 2020",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"3 years",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"148941",title:"Dr.",name:"Mayank",middleName:"Gyan",surname:"Vats",slug:"mayank-vats",fullName:"Mayank Vats",profilePictureURL:"https://mts.intechopen.com/storage/users/148941/images/system/148941.jpg",biography:"Dr. Mayank Vats is a Senior Specialist, Interventional Pulmonologist, Pulmonologist, Intensivist, and Sleep Physician at Rashid Hospital and Dubai Hospital and developed the interventional pulmonology department in Rashid Hospital. Before coming to the United Arab Emirates, he was a consultant in Respiratory Medicine, Critical Care Medicine, and Sleep Medicine at Escorts Heart Institute and Apollo Hospital, New Delhi India, a tertiary level of care hospital in India. Dr Vats’s interest is to utilize his professional knowledge and interpersonal skills in order to provide the highest degree of patient care and satisfaction. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"51006",title:"A Challenged Sympathetic System Is Associated with Retinal Vascular Calibre in a Black Male Cohort: The SABPA Study",doi:"10.5772/63515",slug:"a-challenged-sympathetic-system-is-associated-with-retinal-vascular-calibre-in-a-black-male-cohort-t",body:'\n
\n
1. Introduction
\n
South Africa is facing an epidemic of hypertension (HT) and vascular disease but there still is inadequate information on the physiological factors that are contributing to this process [1, 2]. Microvascular disease seems to play an important role in the development of HT, arterial stiffness and structural remodelling [3]. Currently, HT is regarded as the most important modifiable risk factor for stroke and major macrovascular cerebral complications, but it may also predispose to more subtle cerebral processes based on, amongst others, the microcirculation [4, 5]. Both the ophthalmic artery and the anterior cerebral artery originate from the internal carotid artery and most likely will share common characteristics [6]. Therefore the retinal microvasculature may be an ideal structure to study these abnormalities [7]. Longitudinal studies have shown that an inverse association exists between reduced retinal arteriolar calibre and HT in ageing populations, whilst retinal venular dilation is associated with stroke risk [7, 8]. A higher ratio from either wider retinal arteriolar calibre or narrower retinal venular calibre or both is an index of a better retinal vessel profile [9]. Ref. [8] found racial differences in retinal microvascular calibre of various Asian population groups but whether that is also true for Black and White African men is not clear [8]. In a study using Doppler imagery and iontophoresis of acetylcholine and sodium nitroprusside, it was, however, reported that, after correcting for skin resistance in a Black African group, endothelium-independent microvascular function of Black Africans is attenuated compared to that of White Africans [10]. This might be a contributing factor to the ethnic differences in microvascular disease risk in South Africa.
\n
Enhanced peripheral resistance vascular α-adrenergic responses on exposure to a laboratory stressor, i.e. the handgrip test, were shown in Black Africans during urbanisation when compared to their rural counterparts [11]. Thus overstimulation of the sympathetic nervous system (SNS) and the sympathetic adrenal cortex and medullary stress hormone pathway may explain some of the observed ethnic differences [11–13]. Intense emotional stress may induce sympathetic hyperactivity with persistent increases in catecholamine and cortisol levels, which is detrimental to normal physiological processes [13]. However, during chronic stress this initial hyperactivity may be followed by autonomic exhaustion or depression, receptor hyporesponsivity and decreases in catecholamines and cortisol [14–18]. Phenylethanolamine N-methyltransferase (PNMT) is an enzyme found in the adrenal medulla which converts norepinephrine to epinephrine. PNMT is known to be regulated by glucocorticoids synthesised in the adrenal gland [19]. One-way PNMT expression can be regulated is by corticosterone’s positive influence on the maintenance of PNMT mRNA [20]. Chronic depression has been related to attenuated cortisol levels which will lead to a decrease in the synthesis of epinephrine [21]. These alterations in autonomic function are of importance as they have been associated with both depression and cardiovascular pathology [14, 15]. Moreover, chronic psychosocial stress often precedes depression [22] which, in turn, has recently been acknowledged as a risk factor for cardiac remodelling and poor prognosis in patients with coronary heart disease [23]. Indeed, decreased cortisol and catecholamine metabolite responses to a mental stressor were risk factors for the development of vascular diseases in a Black African cohort exhibiting symptoms of depression [24]. There still remains no clear cut or generally accepted model for cortisol responses in depression, as both blunted and increased cortisol activities have previously been noted [21, 25]. Blunted cortisol responses were apparent in individuals with depressive symptoms after exposure to the Stroop test [13]. This could imply that the presence of depressive symptoms sensitises the individual to stress and the subsequent development of vascular disease and/or other lifestyle illnesses. Blunted cortisol responses to laboratory and psychosocial stressors have been demonstrated in both clinical and subclinical depression [26, 27]. However, it could be speculated that since depression is a constant state of perceived stress, further exposure to a challenging urban environment or psychosocial stress may result in habituation of the neuroendocrine pathways [28].
\n
The 24 h urinary catecholamines and depressive symptoms might, therefore, indicate a challenged SNS associated with retinal microvascular calibre in an urban-dwelling cohort. Whether sympathetic innervation of the retinal vessels exists, is still being debated although it was recently demonstrated that the choroid of the uvea is densely innervated by the sympathetic system and that both α- and β-adrenergic innervations were demonstrated in the preocular central retinal artery (CRA) in humans [29]. The optic canal is a regular conduit for autonomic nerves of the internal carotid plexus to the eye. However, the possible distribution of α- and β-adrenergic receptors in the arterioles of the CRA is still unknown. Generally, in resistance vessels, vasoconstriction is mediated via α1- and α2-adrenergic receptors whilst β2-adrenergic receptors mediate vasodilation [2]. It was recently shown that the CRA receives adrenergic and cholinergic innervation supporting autoregulation of intra-retinal vessels [29]. Systemic sympathetic transmitter spillover (epinephrine and norepinephrine) in the carotid and retinal vasculature may thus impact on retinal perfusion. Indeed, Ref. [30] reported associations of psychosocial risk factors and depression with retinopathy signs (microaneurysms, retinal or vitreous haemorrhages, soft or hard exudates or intra-retinal microvascular abnormalities) and suggested the presence of adrenergic receptors in retinal vessels.
\n
They further demonstrated that heterogeneity in psychosocial effects could result from greater vulnerability of subjects with diabetes and HT due to underlying vascular damage associated with these conditions. This appeared to be the case for symptoms of depression, which had a stronger association with retinopathy in subjects with HT compared with those without, 60% versus 30% greater odds of retinopathy [30].
\n
Chronic stress, as presented by depressive symptoms, may thus induce chronic stimulation of the SNS and initial hyperactivity may be followed by autonomic exhaustion, receptor hyporesponsivity and decreases in catecholamines resulting in hyperkinetic blood pressure (BP) values and receptor hyporesponsivity and decreases in catecholamine levels [15, 16, 31]. The main purpose of this study was, therefore, to assess the associations between retinal microvascular calibre, as primary endpoint and systemic adrenergic neurotransmitters and depressive symptoms, in a bi-ethnic cohort of South African men.
\n
\n
\n
2. Main body of paper
\n
\n
2.1. Materials and methods
\n
\n
2.1.1. Design and participants
\n
Urban Black and White African teachers were recruited as part of the prospective Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) study [32]. All participants of the first phase of SABPA (2007–2008) were invited to participate in the follow-up. Their ages varied between 23 and 68 years. Of the initial 204 male participants in the first phase, 180 men reported for the second phase where, additionally, retinal blood vessel measurements were obtained. Men are more prone to the development of cardiovascular disease (CVD); therefore, only men were included in order to obtain a homogenous high CVD risk cohort [1, 2].
\n
We excluded one participant with a history of epilepsy and 20 participants who did not have usable retinal microvascular images. Finally we included a total of 76 Black and 83 White Africans in the study. Participants were fully informed about the objectives and procedures of the study prior to their recruitment. All participants provided written, informed consent. The study conformed to the Helsinki Declaration (2007) and was approved by the Ethics Review Board of the North-West University, Potchefstroom Campus (approval number 0003607S6).
\n
\n
\n
2.1.2. Assessment of health behaviour
\n
Participants were in a semi-recumbent position from 07 h15 for at least 2 h during which the 12-lead ECG (NORAV PC 1200) registration was performed followed by blood sampling. Physical activity was assessed with the Actiheart® (GB0/67703, CamNtech Ltd., Cambridgeshire, UK) monitors considering resting metabolic rate. The 12-lead ECG resting heart rate was used to calculate the sleep heart rate required by the Actiheart programme. Quantitative assessment of some markers was done to determine smoking status (cotinine, a nicotine metabolite) and alcohol consumption levels (gamma glutamyl transferase, γ-GT) [33]. All anthropometric measurements were performed in triplicate by registered level II anthropometrists according to standardised procedures. The body mass index (BMI) as well as body surface area (BSA) was calculated. BSA was based on the Mosteller formula [34]. Intra- and inter-variability was less than 5%.
\n
\n
\n
2.1.3. Depressive symptoms
\n
The Patient Health Questionnaire (PHQ-9) was used to determine the depressive symptom score of the participants [35]. The PHQ-9 is a measure of depressive symptom severity and has been validated in various ethnic groups including sub-Saharan Africans [36]. The questionnaire is designed for use in primary health-care settings adapting diagnostic criteria from the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition). Each item of the PHQ-9 evaluates the presence of one of the nine DSM-IV criteria of major depression [35]. In the current study, the Cronbach alpha-reliability index for the total PHQ-9 score was 0.80. Items on the questionnaire are scored to reflect the frequency of symptom occurrence during the prior two weeks on a scale of zero to three, with zero reflecting “not at all” and three “nearly every day,” thus providing continuous score between 0 and 27 [35]. Examples of questions are: “Feeling down/depressed/hopeless; feeling bad about yourself OR that you are a failure/that you have let yourself or your family down, thoughts that you would be better off dead/of hurting yourself in some way” [35]. The recommended and established PHQ-9 cut-off point of ≥10 was used to indicate the presence of depressive symptoms [35].
\n
\n
\n
2.1.4. Cardiovascular measurements
\n
On the morning of the first clinical assessment day, ABPM and 2-lead electrocardiograph monitors were attached to participants on the non-dominant arm at their workplace between 07 h00 and 07 h30 (Meditech CE120 CardioTens®; Meditech, Budapest, Hungary). The ABPM was programmed to measure BP at time intervals shown for assessing sympathetic activity at 30-min intervals during the day (07 h00–22 h00) and every hour during night time (22 h00–06 h00) [37]. The successful inflation rate over this period was 85.8% (±9.14) in Africans and 90.4% (±8.61) in Whites. Hypertensive status and CVD risk were classified from 24 h ABPM as systolic blood pressure (SBP) ≥ 130 mmHg and/or diastolic blood pressure (DBP) ≥ 80 mmHg [38]. Hyperpulsatile pulse pressure (PP) was defined as 24 h SBP–24 h DBP > 50 mmHg [39]. The apparatus was removed after the last BP measurement at 07 h30 the next day.
\n
\n
\n
2.1.5. Measurement of retinal vascular calibre
\n
Static retinal microvascular measurements were performed in a well-controlled light and temperature regulated laboratory using an Imedos Retinal Vessel Analyser (Germany) with a Zeiss FF450Plus camera and the VesselMap 1 Version 3.10 software. No intake of food or caffeine containing beverages, alcohol, smoking or exercise was allowed one hour prior to retinal vessel measurements. Participants were introduced to the procedure and screened for Acute angle-closure glaucoma risk with a small light source by a trained registered nurse. Mydriasis was induced in the right eye of the participant by means of a drop containing tropicamide 1% and benzalkonium chloride 0.01% (m/v). In the event of previous injury to the right eye, the left eye was used (Black men N = 3; White men N = 1). Retinal vascular calibre was measured in the monochrome images by manually selecting first-order vessel branches in a measuring zone located between 0.5 and 1.0 optic disc diameters from the margin or the optic disc. Upon selection of the vessel, the VesselMap 2, Version 3.02 software, automatically delineated the vessels’ measuring area. The colour photograph was used as a reference to ascertain correct identification of venules and arterioles. Identification of vessels was done by two experienced scientists who had to agree on the vessel type before selection. Automated software calculations, based on the Knudtson revision of the Parr-Hubbard formulas, determined estimates from the six largest arterioles and venules and were summarised as the central retinal arterial equivalent (CRAE) and central retinal venular equivalent (CRVE), respectively [40]. AVR was also calculated (CRAE/CRVE). Arterio-venular nicking was defined when a small arteriole crossed a small venule and resulted in the compression of the vein with bulging on either side of the crossing. A higher ratio from either wider retinal arteriolar calibre or narrower retinal venular calibre or both is an index of a better retinal vessel profile [9]. As the image scale of each eye was unknown, the values of CRAE and CRVE were expressed as measuring units (MU). 1 MU is equivalent to 1 μm when the dimensions of the eye being examined correspond to those of the normal Gullstrand eye. Reproducibility was computed for a randomly selected cohort with a correlation coefficient of 0.84. The ICC analysis involved a mixed-model framework, whereby random effects were assumed for subjects and fixed effects were assumed for the graders. The Cronbach’s alpha-reliability index for the AVR was 0.91 for this randomised cohort. Retinal pathology as seen in hypertensive/diabetic retinopathy and including optic nerve cup/disc ratio and arterio-venular nicking was diagnosed by a registered ophthalmologist.
\n
\n
\n
2.1.6. 24 h urinary catecholamines
\n
A three-litre container, washed with 9 ml of 20% HCl, ensured preservation of urinary metanephrines and an accurately 24 h timed specimen (Sarstedt®, Nümbrecht, Germany). Sampling began and ended with an empty bladder and participants were instructed to complete a 24 h diary to indicate voiding time, volume and fluid intake.
\n
\n
\n
2.1.7. Biochemical analyses
\n
Sodium fluoride blood samples, serum and whole blood EDTA samples were analysed for glucose, lipids, C-reactive protein (CRP), cotinine, γ-GT and glycated haemoglobin (HbA1c), using Unicel DXC 800 (Beckman and Coulter, USA), Modular ROCHE Automized (Switzerland) and the KonelabTM 20I Sequential Multiple Analyzer Computer (ThermoScientific, Vantaa, Finland), respectively. An acidified sample from the 24 h urine collection was stored at −80°C until analysis within one year after collection [41]. Urinary epinephrine and norepinephrine values were determined using the 3-Cat Urine ELISA Fast Track kit (LDN, Nordhorn, Germany). Intra- and inter-assay coefficients for epinephrine were 5.50% and 9.62%, respectively, and for norepinephrine 2.70% and 8.59%.
\n
\n
\n
2.1.8. Statistical methods
\n
Data were analysed using Statistica® software version 12.0 (Statsoft Inc., Tulsa, USA, 2012). Skewness of data was tested and γ-GT and CRP values were logarithmically transformed. Independent T-tests determined participant characteristic differences. A priori covariates which are implicated in higher sympathetic activity and CVD risk included age, BSA, physical activity, log γ-GT, log CRP and cholesterol [33, 38]. Chi-square (χ2) statistics compared proportions. General linear model analyses, independent of a priori covariates, were computed to test interactions with race for depressive symptoms, norepinephrine-to-creatinine ratio (NECR), epinephrine-to-creatinine ratio (ECR) and potential cardiovascular risk markers (i.e. PP) and retinal vasculature markers, and, as a result of the high correlation between CRAE and CRVE, CRAE was adjusted for CRVE and vice versa [42]. ANCOVA’s determined significant differences by comparing ethnic male groups from least square means analyses whilst adjusting for covariates (age, BSA, physical activity, log γ-GT, log CRP, cholesterol).
\n
Multiple linear regression analyses were computed in the total male cohort and in separate race groups. Unadjusted associations between retinal vessel calibre markers, depressive symptoms and catecholamines were computed in the male cohorts. Forward stepwise multiple regression analyses were performed in various models based on significant interactions for race. Dependent variables were AVR, CRVE and CRAE. Independent covariates included age, BSA, physical activity, log γ-GT, log CRP, cholesterol 24 h PP, depressive symptoms, NECR and ECR. As a result of the high correlation between CRAE and CRVE, CRAE was added as covariate for CRVE and vice versa.
\n
Sensitivity analyses: Forward stepwise regression analyses with similar dependent and independent covariates were repeated in several models in both ethnic male groups, by (a) excluding HIV-positive status participants (N = 16) (b) including only 24 h hypertensive participants and (c) adding HT medication users, cotinine and/or serum glucose as independent covariates. Significance was noted as p ≤ 0.05.
\n
\n
\n
\n
2.2. Results
\n
General linear model analyses showed ethnic differences for principal variables investigated, NECR and ECR (F1.151 = 20.66, p < 0.0001), depressive symptoms (F1.165 = 4.45, p = 0.04) as well as AVR (F1.150 = 9.09, p = 0.003), independent of a priori covariates.
\n
\nTable 1 shows unadjusted baseline characteristics of the Black and White men. The Black men displayed lower waist circumference, BSA, BMI and physical activity but a larger metabolic risk with higher glucose, HbA1c, cholesterol, CRP and γ-GT than their White counterparts. They also had a higher depressive symptom score with 34.2% of the Black men above the cut-off point for modestly severe depressive symptoms [36] compared to 13.3% of the White men. Despite their higher depressive symptom score, the Black men had lower 24 h urine NECR and 24 h urine ECR ratios than the White men. The Black group had higher BP, PP, arterio-venular nicking, optic nerve cup/disc ratio and CRVE values, whilst their retinal AVR was smaller compared to that of the White group.
\n
\n
\n
\n
\n
\n\n
\n
\n
Black men (N = 76)
\n
White men (N = 83)
\n
P
\n
\n\n\n
\n
\nLifestyle and biochemical variables\n
\n
\n
\n
Age (years)
\n
45.4 ± 6.9
\n
48.8 ± 10.2
\n
0.016
\n
\n
\n
BMI (kg/m2)
\n
28.4 ± 5.77
\n
30.4 ± 5.24
\n
0.026
\n
\n
\n
BSA (m2)
\n
1.99 ± 0.22
\n
2.24 ± 0.21
\n
<0.0011
\n
\n
\n
Waist circumference (cm)
\n
98.3 ± 14.8
\n
106.2 ± 13.2
\n
<0.001
\n
\n
\n
Physical activity (kcal/24 h)
\n
3464.2 ± 1284.5
\n
4101.2 ± 1859.2
\n
0.015
\n
\n
\n
Cholesterol (mmol/L)
\n
4.63 ± 1.02
\n
4.22 ± 1.00
\n
0.012
\n
\n
\n
HDL cholesterol (mmol/L)
\n
0.93 ± 0.35
\n
0.84 ± 0.22
\n
0.054
\n
\n
\n
Glucose (mmol/L)
\n
5.75 ± 1.71
\n
4.65 ± 1.30
\n
<0.001
\n
\n
\n
Glycated haemoglobin (%)
\n
6.18 ± 1.40
\n
5.70 ± 0.88
\n
0.010
\n
\n
\n
γ-Glutamyl transferase (U/L)
\n
71.7 ± 61.9
\n
36.7 ± 41.2
\n
<0.001
\n
\n
\n
C-reactive protein (mg/L)
\n
5.91 ± 12.2
\n
2.84 ± 10.0
\n
0.084
\n
\n
\n
Cotinine (ng/mL)
\n
48.3 ± 97.8
\n
29.5 ± 98.7
\n
0.232
\n
\n
\n
Depressive symptoms score
\n
7.59 ± 4.51
\n
4.86 ± 4.23
\n
<0.0011
\n
\n
\n
Depressive symptoms (PHQ-9 ≥ 10) N (%))
\n
26 (34.2)
\n
11 (13.3)
\n
<0.001
\n
\n
\n
\n24 h endocrine variables\n
\n
\n
\n
24 h urine norepinephrine/creatinine ratio (nmol/mmol)
\n
15.3 ± 10.7
\n
28.4 ± 20.5
\n
<0.001
\n
\n
\n
24 h urine epinephrine/creatinine ratio (nmol/mmol)
\n
2.61 ± 1.70
\n
4.71 ± 3.17
\n
<0.001
\n
\n
\n
\nCardiovascular variables\n
\n
\n
\n
24 h SBP (mmHg)
\n
137 ± 15
\n
128 ± 11
\n
<0.001
\n
\n
\n
24 h DBP (mmHg)
\n
87 ± 10
\n
80 ± 7
\n
<0.001
\n
\n
\n
24 h PP (mmHg)
\n
51 ± 8
\n
48 ± 6
\n
0.034
\n
\n
\n
24 h heart rate (beats/min)
\n
78 ± 9
\n
72 ± 10
\n
<0.001
\n
\n
\n
Central retinal arterial equivalent (MU)
\n
147.9 ± 13.2
\n
150.4 ± 11.9
\n
0.218
\n
\n
\n
Central retinal venular equivalent (MU)
\n
251.4 ± 19.2
\n
237.9 ± 18.6
\n
<0.001
\n
\n
\n
Retinal arteriolar-to-venular ratio
\n
0.59 ± 0.06
\n
0.63 ± 0.04
\n
<0.001
\n
\n
\n
Optic nerve cup/disc ratio (right eye)
\n
0.37 ± 0.19
\n
0.28 ± 0.24
\n
0.011
\n
\n
\n
Hypertensive/diabetic retinopathy (%)
\n
75.0
\n
36.3
\n
<0.001
\n
\n
\n
Arterio-venular nicking (N (%))
\n
59 (77.6)
\n
20 (24.1)
\n
<0.001
\n
\n
\n
HT (SBP > 130 and/or DBP > 80 mmHg) (N (%))
\n
60 (78.9)
\n
40 (48.4)
\n
0.001
\n
\n
\n
HT medication (% of hypertensives)
\n
36.6
\n
34.1
\n
0.274
\n
\n\n
Table 1.
Comparing unadjusted mean (±SD) baseline characteristics of Black and White men.
Data presented as unadjusted means with standard deviation or percentages. Where BMI, body mass index; BSA, body surface area; PHQ, Patient Health Questionnaire; 24 h SBP, 24 h systolic blood pressure; 24 h DBP, 24 h diastolic blood pressure; 24 h PP, 24 h pulse pressure; HT, hypertension; MU, measuring units, equal to μm in the normal Gullstrand eye.
\n
In Table 2, principal variables were compared considering a priori covariates. In the Black male cohort, a similar trend was revealed with increased hyperpulsatile PP (>50 mmHg) accompanied by more depressive symptoms, lower AVR and also lower urine NECR and ECR values compared to their White counterparts. However, only the AVR was smaller in the Blacks whilst neither CRAE nor CRVE was different between the race groups.
\n
\n
\n
\n
\n
\n\n
\n
\n
Black men (N = 76)
\n
White men (N = 83)
\n
P
\n
\n\n\n
\n
24 h SBP (mmHg)
\n
140 (137, 144)
\n
126 (123, 130)
\n
<0.001
\n
\n
\n
24 h DBP (mmHg)
\n
88 (86, 90)
\n
79 (77, 81)
\n
<0.001
\n
\n
\n
24 h PP (mmHg)
\n
52 (50, 54)
\n
47 (45, 50)
\n
<0.001
\n
\n
\n
Central retinal arterial equivalent (MU)
\n
147.4 (144.0, 150.8)
\n
150.9 (147.6, 154.1)
\n
0.21
\n
\n
\n
Central retinal venular equivalent (MU)
\n
248.0 (242.9, 253.1)
\n
241.2 (236.4, 246.1)
\n
0.11
\n
\n
\n
Retinal arteriolar-to-venular ratio
\n
0.60 (0.58, 0.61)
\n
0.63 (0.61, 0.64)
\n
0.01
\n
\n
\n
24 h urine ECR (nmol/mmol)
\n
14.3 (9.76, 18.9)
\n
30.0 (25.7, 34.3)
\n
<0.001
\n
\n
\n
24 h urine NECR (nmol/mmol)
\n
2.08 (1.14, 3.02)
\n
5.82 (4.94, 6.69)
\n
<0.001
\n
\n
\n
Depressive symptom score
\n
7.11 (6.02, 8.21)
\n
4.71 (3.84, 5.79)
\n
0.006
\n
\n\n
Table 2.
Comparing adjusted mean (±95% CI) baseline characteristics of Black and White men.
Comparing adjusted mean (± SD) pulse pressure, retinal vessel calibre, depressive symptoms and 24 h urinary catecholamines in a cohort of Black and White men. Values were adjusted for age, body surface area, physical activity, log γ-glutamyl transferase, log C-reactive protein and cholesterol. Where 24 h SBP, 24 h systolic blood pressure; 24 h DBP, 24 h diastolic blood pressure; 24 h PP, 24 h pulse pressure; MU, measuring units, equal to μm in the normal Gullstrand eye; 24 h NECR ratio, 24 h urinary norepinephrine-to-creatinine ratio; 24 h ECR ratio, 24 h urinary epinephrine-to-creatinine ratio.
\n
Forward stepwise linear regression analyses (Table 3) revealed expected patterns of associations between the dependent retinal microvascular calibre variables (AVR, CRAE and CRVE) and independent variable, PP, in the total group (Model 1). AVR and CRAE were negatively associated with PP, whilst CRVE showed a positive association with PP. In the total group, negative associations were found between AVR, CRAE and depressive symptoms, whilst no associations were found between any of the retinal microvascular variables and NECR or ECR. In the separate ethnic groups, AVR was negatively associated with PP in both racial groups. CRAE was negatively associated with PP in the White men whilst positively associated with CRVE in the Black men. In the White group, AVR and CRAE were negatively associated with depressive symptoms, whilst AVR was, rather unexpectedly, positively associated with NECR. In the Black group, AVR and CRAE were negatively associated with ECR, whilst a positive association existed with CRVE. No unadjusted or adjusted associations between depressive symptoms and the catecholamines were revealed (data not shown).
\n
No changes in the outcome of the data occurred with sensitivity analyses after excluding HIV-positive status participants or including 24 h hypertensive participants. Adding HT medication users, cotinine and serum glucose as independent covariates also did not alter any of the associations.
\n
\n
\n
\n
\n
\n\n
\n
Model 1: Total group (N = 159)
\n
\n
\n
\n
AVR
\n
CRAE
\n
CRVE
\n
\n
\n
Adjusted R2
\n
0.28
\n
0.36
\n
0.39
\n
\n\n\n
\n
β (95% CI)
\n
\n
\n
Race
\n
0.16 (0.002, 0.32), p = 0.049
\n
–
\n
−0.20 (−0.36,−0.04), p = 0.017
\n
\n
\n
24 h PP (mmHg)
\n
−0.24 (−0.38,−0.10), p = 0.001
\n
−0.24 (−0.38,−0.11), p = 0.001
\n
0.17 (0.04, 0.31), p = 0.014
\n
\n
\n
Depressive symptoms
\n
−0.19 (−0.34,−0.05), p = 0.014
\n
−0.23 (−0.30,−0.15), p = 0.001
\n
–
\n
\n
\n
24 h urine ECR
\n
–
\n
–
\n
NS
\n
\n
\n
24 h urine NECR
\n
–
\n
NS
\n
–
\n
\n\n
Covariates included age, body surface area, physical activity, log γ-glutamyl transferase, log C-reactive protein and cholesterol. In models with CRAE as a dependent variable, adjustment for CRVE was made and vice versa. Where AVR, arteriolar-to-venular ratio; CRAE, central retinal arterial equivalent; CRVE, central retinal venular equivalent; 24 h PP, 24 h pulse pressure; ECR, epinephrine-to-creatinine ratio; NECR, norepinephrine-to-creatinine ratio.
\n
\n
\n
\n
\n
\n\n
\n
Model 2: Separate ethnic groups
\n
\n
\n
\n
Black men (N = 76)
\n
White men (N = 83)
\n
\n
\n
\n
AVR
\n
CRAE
\n
CRVE
\n
AVR
\n
CRAE
\n
CRVE
\n
\n
\n
Adjusted R2
\n
0.24
\n
0.15
\n
0.29
\n
0.27
\n
0.59
\n
0.52
\n
\n\n\n
\n
β (95% CI)
\n
\n
\n
24 h PP (mmHg)
\n
−0.24 (−0.46,−0.01), p = 0.048
\n
–
\n
0.23 (0.01, 0.45), p = 0.045
\n
−0.30 (−0.48,−0.11), p = 0.003
\n
−0.22 (−0.36,−0.08), p = 0.003
\n
–
\n
\n
\n
Depressive symptoms
\n
–
\n
–
\n
–
\n
−0.27 (−0.46,−0.08), p = 0.007
\n
−0.18 (−0.32,−0.04), p = 0.014
\n
–
\n
\n
\n
24 h urine ECR (nmol/mmol)
\n
−0.35 (−0.57,−0.12), p = 0.004
\n
−0.37 (−0.66,−0.09), p = 0.013
\n
0.35 (0.13, 0.57), p = 0.003
\n
–
\n
\n
–
\n
\n
\n
24 h urine NECR (nmol/mmol)
\n
–
\n
NS
\n
–
\n
0.19 (0.0, 0.38), p = 0.050
\n
\n
–
\n
\n\n
Table 3.
Forward stepwise regression analyses predicting relationships between the 24 h urinary catecholamine levels, depressive symptoms and retinal vessel parameters.
Covariates included age, body surface area, physical activity, log γ-glutamyl transferase, log C-reactive protein and cholesterol. In models with CRAE as a dependent variable, adjustment for CRVE was made and vice versa. Where AVR, arteriolar-to-venular ratio; CRAE, central retinal arterial equivalent; CRVE, central retinal venular equivalent; 24 h PP, 24 h pulse pressure; ECR, epinephrine-to-creatinine ratio; NECR, norepinephrine-to-creatinine ratio; NECR, norepinephrine-to-creatinine ratio.
\n
\n
\n
2.3. Discussion
\n
The aim of this study was to evaluate the association between the retinal microvascular calibre as primary endpoint and systemic adrenergic transmitters and depressive symptoms as independent variables, comparing a Black and White male cohort from South Africa.
\n
The main novel finding suggests a cardiometabolic vulnerable profile in terms of more depressive symptoms, PP, arterio-venular nicking, optic nerve cup/disc ratio and CRVE values, whilst their retinal AVR was smaller in the Black men. Despite lower catecholamine levels, epinephrine was positively associated with arteriolar narrowing, venular widening and hyperpulsatile BP (indicative of arterial stiffness) in the Black men.
\n
\n
2.3.1. Ethnicity and retinopathy
\n
Although cultural differences exist between the Black and White groups, all the participants were teachers with the same educational background, income and working conditions. Despite these similarities, the Black group clearly exhibited a poorer health profile than their White counterparts with regard to cardiometabolic and mental health characteristics. They presented with increased cardiometabolic risk markers such as hyperglycaemia, cholesterol, inflammation, alcohol consumption and depressive symptoms. The Black group’s mean BP values were above the cut-off point for HT (ABPM ≥ 130/80) [38], which reflect in the HT prevalence of nearly 80% in this group. Elevated BP and PP are associated with structural microvascular changes and our findings are in line with those references [43, 44]. Indeed, elevated BP and PP were associated with attenuated retinal arteriolar and increased venular diameter values and consequently also the AVR. This may impact on vascular wall remodelling as is evident from the presence of arteriolar narrowing, AV nicking, retinopathy [45] and possibly progression towards subclinical atherosclerosis. If the effect of elevated glucose as well as HbA1c levels is added which, in the case of the Black men, are both, according to the American Diabetes Association, above the cut-off point indicative of a prediabetic state, changes in the retinal vessels comparable to those in diabetic subjects could be expected. The prevalence of AV nicking and hypertensive/diabetic retinopathy is a clear indication.. that the retinal vasculature is showing signs of structural changes and reduced microvascular health in both groups but especially in the Black group.
\n
\n
\n
2.3.2. Retinal vessel calibre and depressive symptoms
\n
Depression has recently been acknowledged as a major risk factor for poorer prognosis in patients with coronary heart disease by the American Heart Association [23]. The depressive symptom score of the Black men was significantly higher than that of the White men with 34 % of the group exceeding the cut-off point for moderately severe depression, thereby worsening their CVD risk. Although underlying stress levels, as assessed using the depressive symptoms risk score, were elevated in the Black men, both their 24 h ECR and NECR levels were lower compared to their White counterparts. During chronic stress the initial hyperactivity may be followed by autonomic exhaustion, receptor hyporesponsivity and decreases in catecholamines and cortisol [14–18]. PNMT converts norepinephrine to epinephrine and is regulated by glucocorticoids synthesised in the adrenal gland [19]. One way that it can regulate PNMT expression is by corticosterone’s positive influence on the maintenance of PNMT mRNA [20]. Therefore a reduction in cortisol will lead to a decrease in the synthesis of epinephrine. These alterations in autonomic function are of importance as they have been associated with both depression and cardiovascular pathology [14, 15]. It is known that depression is often preceded by psychosocial stress [22] which might, therefore, also be associated with the risk for cardiac remodelling as well as a poor prognosis in individuals with coronary heart disease [23]. This notion is enhanced by the finding that in a Black cohort with symptoms of depression, attenuated cortisol and catecholamine metabolites were identified as risk factors for the development of vascular diseases [24]. Even though depression [46], diabetes and HT are associated with activation of the SNS [31], we could not replicate these findings.
\n
Our results, therefore, oppose the findings from Ref. [47], showing a positive association between NECR excretion and moderate depressive symptoms. As more depressive symptoms and a hypertensive state are evident in the Black men, the SNS and adrenal medulla may present neural fatigue or “burnout.” Our findings could, therefore, indicate a possible down-regulation of norepinephrine and epinephrine secretion as a consequence of long-term overstimulation of the SNS and possible β-adrenergic hyporesponsivity in the Black men. In support of this notion, depressed heart rate variability (HRV) was associated with increased parasympathetic dominance albeit cardiac contractility (24-h heart rate and SBP) in the current African men at baseline, rather suggesting β-adrenergic receptor activation [1, 48]. Conversely, increased SNS activity and a possible vagal-impaired HR profile may however contribute to disturbed endothelial function, possibly because of activation of β-adrenergic receptors [49]. When α-adrenergic responsiveness though prevails [48], dysregulation or desensitisation of β-adrenergic receptors may occur. This was evident in the clustering of increased 24-h heart rate, SBP and depressed HRV values which indicated a possible diminished β-adrenergic responsiveness and vagal-impaired response [1]. A plausible explanation may be that depressed HRV as a reflection of α-adrenergic sympathetic overdrive could also be due to poor ventricular performance as was observed in another study [50].
\n
It supports previous findings in these SABPA Black men, where blunted neuroendocrine responses were associated with vascular wall remodelling concurring with a profile of autonomic exhaustion and emotional distress [14, 16]. Our subsample of White men showed a 13% prevalence of depressive symptoms which were inversely associated with the retinal vessel calibre. Findings from the ARIC study compare favourably with the White group where the depressive symptom score was associated with retinal arteriolar narrowing. In contrast, we could not replicate these findings in the Black group. Clearly prospective studies are needed to determine causality [30].
\n
\n
\n
2.3.3. Retinal microvascular calibre and catecholamines
\n
SNS activation is present in both diabetes and HT [31] and may be associated with microvascular calibre. Increased perfusion pressure enforces…. contraction in the ocular arteries, which are resistance vessels and regulated by myogenic mechanisms (Bayliss effect) [51]. Retinal microvascular calibre associations with the adrenergic transmitters revealed different profiles in the two ethnic groups. Chronic SNS activation will desensitise the baroreceptors with compensatory increases in BP and PP as was shown in the Black group [1]. In the Black group, the smaller CRAE and a larger CRVE are both associated with epinephrine but not with norepinephrine levels. This may imply that epinephrine will reduce blood flow to the retina by stimulating arteriolar contraction but also increasing the draining of blood away from the retina by stimulating venular dilation. Myogenic tone may however be impaired in Blacks and increase retinal venular widening especially during chronic pressure overload with increased hyperpulsatility. An overactive sympathetic system and/or chronic depression symptoms might therefore explain part of the mechanism. Presently, instead of epinephrine’s normal arterial vasodilatory response [52], it induces vasoconstriction, which may suggest hyporesponsivity or down-regulation of the β2-adrenergic receptors as was also shown previously [1]. Therefore, this hyporesponsivity may be a homeostatic reaction to protect the retina from SNS-stimulated increases in hyperpulsatile pressure in a cohort who has more depressive symptoms. This may be true for both the retina and the brain as emotional stress can also provoke reversible cerebral vasoconstriction similar to retinal vasoconstriction [53].
\n
Both a smaller AVR and a larger CRVE are associated with a greater risk for stroke mortality [7]. This also suggests that β-adrenoceptor hyporesponsivity due to SNS hyperactivity as reflected in lower catecholamine levels might constitute an increased risk for vascular hypertrophy and eventually stroke in the Black male cohort. The same associations were not seen in the White men, maybe as result of their lower depressive symptom scores as well as their lower BP and PP levels. The prevalence of depressive symptoms and possible down-regulated catecholamine profile presuming chronic distress in the Black men compared to their White counterparts, therefore, may explain the differences or lack of association between the catecholamine levels and AVR in the Whites.
\n
\n
\n
2.3.4. Retinal microvascular calibre and local or systemic sympathetic activation
\n
Whether local or systemic catecholamine levels are associated with retinopathy is hotly debated [29, 30]. Recently, both α- and β-adrenergic innervation was demonstrated in the preocular CRA in humans [29]. It seems clear that some aspects of sympathetic transmission regulate choroidal and CRA blood flow by way of changes in vascular smooth muscle tone [54]. The inverse association between AVR and ECR may support a vasodilatory (venular) or vasoconstrictive (arteriolar) tone in the retinal vessels. A notion for vasoconstriction is suggested as a hypertensive state increases peripheral vascular resistance in the retinal arterioles [7]. Therefore, increased or hyperpulsatile PP exerting mechanical stress on the vessel walls may contribute to a diminished β-adrenergic albeit an augmented α-adrenergic responsiveness in Black men [1, 33] and subsequent risk of vascular hypertrophy [1] and possibly arteriolar narrowing. The profile of β-adrenergic hyporesponsivity in Black men emphasises central control of the brain on the circulatory system irrespective of the vascular bed.
\n
Several limitations should be noted. The cross-sectional design of the current study prevents us from being able to infer causality. Studies showing direct evidence of sympathetic tone and retinal vascular remodelling in human models could greatly contribute to our knowledge in this field. Larger sample sizes and more diverse data on autonomic and endothelial function are needed to delineate possible physiological mechanisms and the role of the ageing process. Only an indirect measure of SNS activity via 24 h catecholamine concentrations was measured and more direct measurements should be implemented, along with the determination of the corticosteroid profile. A more representative sample of the whole population is necessary to draw generalised conclusions.
\n
\n
\n
\n
2.4. Conclusions
\n
A profile of β-adrenergic hyporesponsivity was evident in Black men. They revealed more depressive symptoms, indicative of a chronically challenged SNS, which were associated with retinal vascular remodelling and possible vascular hypertrophy. Whether these changes precede or result from hyperpulsatile pressure impacting on retinal autoregulation is still debatable.
\n
\n
\n
Acknowledgments
\n
The present work was partially supported by the North-West Department of Education, South African Medical Research Council, National Research Foundation, North-West University, ROCHE Diagnostics, South Africa, and Metabolic Syndrome Institute, France. We gratefully acknowledge the voluntary collaboration of the participants. The SABPA study would not have been possible without the valuable contributions of co-investigators and technical staff.
\n\n
The present work was partially supported by the North-West Department of Education, South African Medical Research Council, National Research Foundation, North-West University, ROCHE Diagnostics, South Africa, and the Metabolic Syndrome Institute, France. None of the funding sources had any other involvement in the study design, data collection, analysis or interpretation or in the writing of the manuscript.
\n
Compliance with ethical standards: The ethics on publishing scientific articles were followed. The authors report no relationships that could be construed as a conflict of interest. Any opinion, findings and conclusions or recommendations expressed in this material are those of the author(s) and therefore the NRFs do not accept any liability in regard thereto.
\n\n
ambulatory blood pressure measurement (ABPM)
arteriolar-to-venular ratio (AVR)
blood pressure (BP)
body surface area (BSA)
body mass index (BMI)
cardiovascular disease (CVD)
central retinal arterial equivalent (CRAE)
central retinal artery (CRA)
central retinal venular equivalent (CRVE)
C-reactive protein (CRP)
diastolic blood pressure (DBP)
electrocardiogram (ECG)
epinephrine-to-creatinine ratio (ECR)
gamma glutamyl transferase (γ-GT)
glycated haemoglobin (HbA1c)
heart rate variability (HRV)
hypertension (HT)
measuring units, equal to μm in the normal Gullstrand eye (MU)
norepinephrine-to-creatinine ratio (NECR)
Patient Health Questionnaire (PHQ-9)
phenylethanolamine N-methyltransferase (PNMT)
pulse pressure (PP)
Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) study
sympathetic nervous system (SNS)
systolic blood pressure (SBP)
\n
\n',keywords:"Africans, retinal microvascular calibre, 24 h urinary epinephrine, depressive symptoms, ethnicity",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/51006.pdf",chapterXML:"https://mts.intechopen.com/source/xml/51006.xml",downloadPdfUrl:"/chapter/pdf-download/51006",previewPdfUrl:"/chapter/pdf-preview/51006",totalDownloads:1670,totalViews:235,totalCrossrefCites:3,totalDimensionsCites:7,totalAltmetricsMentions:0,impactScore:5,impactScorePercentile:94,impactScoreQuartile:4,hasAltmetrics:0,dateSubmitted:"December 1st 2015",dateReviewed:"April 7th 2016",datePrePublished:null,datePublished:"October 26th 2016",dateFinished:"June 7th 2016",readingETA:"0",abstract:"Sympathetic system hyperactivity and depression are related to cardiac remodelling in Black men. We investigated whether sympathetic system hyperactivity and depressive symptoms are related to retinal vascular dysregulation. A total of 76 Black and 83 White men (23–68 years of age) from the SABPA study were included. Depressive symptoms, 24h pulse pressure (PP), fasting blood and 24-hour urinary catecholamine data were obtained. Retinal vascular calibre was quantified from digital photographs using standardized protocols. Black men demonstrated increased (p < 0.05) hyperpulsatile pressure (PP > 50 mmHg), hypertension (78.9 % vs 48.4%) and depression (34.2% vs. 13.3%) prevalence compared to White men. Despite lower epinephrine levels, epinephrine was associated with arteriolar narrowing and venular widening in the Black men [Adj R2 −0.37 (95% CI: −0.66, −0.09), p=0.013; Adj R2 0.35 (95% CI: 0.13, 0.57), p=0.003]. This might suggest ß-adrenergic hyporesponsivity to epinephrine, which was accompanied by hyperpulsatile blood pressure in the Black group. In the White group, depressive symptoms and norepinephrine were associated with retinal arteriolar narrowing. A profile of ß-adrenergic hyporesponsivity, indicative of a chronically challenged sympathetic system, was associated with retinal vascular remodelling in Black men. ß-adrenergic hyporesponsivity as a result of chronic stress emphasized central control of the brain on the circulatory system irrespective of the vascular bed.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/51006",risUrl:"/chapter/ris/51006",book:{id:"5281",slug:"microcirculation-revisited-from-molecules-to-clinical-practice"},signatures:"Nicolaas T. Malan, Roland von Känel, Wayne Smith, Gavin W.\nLambert, Walthard Vilser, Nina Eikelis, Manja Reimann and Leoné\nMalan",authors:[{id:"183353",title:"Prof.",name:"Leoné",middleName:null,surname:"Malan",fullName:"Leoné Malan",slug:"leone-malan",email:"leone.malan@nwu.ac.za",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"North-West University",institutionURL:null,country:{name:"South Africa"}}},{id:"183428",title:"Prof.",name:"Gavin W",middleName:null,surname:"Lambert",fullName:"Gavin W Lambert",slug:"gavin-w-lambert",email:"gavin.lambert@bakeridi.edu.au",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"183429",title:"Prof.",name:"Roland",middleName:null,surname:"Von Kaenel",fullName:"Roland Von Kaenel",slug:"roland-von-kaenel",email:"roland.vonkaenel@barmelweid.ch",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"183430",title:"Prof.",name:"Nicolaas T",middleName:null,surname:"Malan",fullName:"Nicolaas T Malan",slug:"nicolaas-t-malan",email:"nico.malan@nwu.ac.za",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"183431",title:"Dr.",name:"Wayne",middleName:null,surname:"Smith",fullName:"Wayne Smith",slug:"wayne-smith",email:"wayne.smith@nwu.ac.za",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"183432",title:"Prof.",name:"Walthard",middleName:null,surname:"Vilser",fullName:"Walthard Vilser",slug:"walthard-vilser",email:"walthard.vilser@imedos.de",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"183441",title:"Dr.",name:"Nina",middleName:null,surname:"Eikelis",fullName:"Nina Eikelis",slug:"nina-eikelis",email:"nina.eikelis@bakeridi.edu.au",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"183443",title:"Dr.",name:"Manja",middleName:null,surname:"Reimann",fullName:"Manja Reimann",slug:"manja-reimann",email:"Manja.reimann@uniklinikum-dresden.de",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Main body of paper",level:"1"},{id:"sec_2_2",title:"2.1. Materials and methods",level:"2"},{id:"sec_2_3",title:"2.1.1. Design and participants",level:"3"},{id:"sec_3_3",title:"2.1.2. Assessment of health behaviour",level:"3"},{id:"sec_4_3",title:"2.1.3. Depressive symptoms",level:"3"},{id:"sec_5_3",title:"2.1.4. Cardiovascular measurements",level:"3"},{id:"sec_6_3",title:"2.1.5. Measurement of retinal vascular calibre",level:"3"},{id:"sec_7_3",title:"2.1.6. 24 h urinary catecholamines",level:"3"},{id:"sec_8_3",title:"2.1.7. Biochemical analyses",level:"3"},{id:"sec_9_3",title:"2.1.8. Statistical methods",level:"3"},{id:"sec_11_2",title:"2.2. Results",level:"2"},{id:"sec_12_2",title:"2.3. Discussion",level:"2"},{id:"sec_12_3",title:"2.3.1. Ethnicity and retinopathy",level:"3"},{id:"sec_13_3",title:"2.3.2. Retinal vessel calibre and depressive symptoms",level:"3"},{id:"sec_14_3",title:"2.3.3. Retinal microvascular calibre and catecholamines",level:"3"},{id:"sec_15_3",title:"2.3.4. Retinal microvascular calibre and local or systemic sympathetic activation",level:"3"},{id:"sec_17_2",title:"2.4. Conclusions",level:"2"},{id:"sec_19",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'\nMalan L, Hamer M, Schlaich MP, et al. Defensive coping facilitates higher blood pressure and early sub-clinical structural vascular disease via alterations in heart rate variability: the SABPA study. Atherosclerosis 2013;227:391–97.\n'},{id:"B2",body:'\nOpie LH, Seedat YK. Hypertension in Sub-Saharan populations. Circulation 2005;112:3562–68.\n'},{id:"B3",body:'\nRizzoni D, Porteri E, Castellano M, et al. Vascular hypertrophy and remodelling in secondary hypertension. Hypertrophy 1996;28:785–90.\n'},{id:"B4",body:'\nSierra C. Cerebral small vessel disease, cognitive impairment and vascular dementia. Panminerva Med 2012;54:179–188.\n'},{id:"B5",body:'\nMalan L, Hamer M, von Känel R, et al. Chronic depression symptoms and salivary NOx associated with retinal vascular dysregulation: the SABPA study. Nitric Oxide 2016;55–56:11–17. doi: 1016/j.niox.2016.02.008.\n'},{id:"B6",body:'\nPatton N, Aslam T, MacGillivray A, et al. Retinal vascular image analysis a potential screening tool for cerebrovascualr disease: a rationale based on homology between cerebral and retinal microvasculatures. J Anat 2005;206:319–48.\n'},{id:"B7",body:'\nCheung CY, Ikram K, Sabanayagam C, Wong TY. Retinal microvasculature as a model to study the manifestations of hypertension. Hypertension 2012;60:1094–103.\n'},{id:"B8",body:'\n Li X, Wong LL, Cheung CY, et al. Racial differences in retinal vessel geometric characteristics: a multiethnic study in healthy Asians. Invest Ophthalmol Vis Sci 2013;54:3650–56.\n'},{id:"B9",body:'\nHenderson AD, Bruce BB, Newman NJ, Biousse V. Hypertension-related eye abnormalities and the risk of stroke. Rev Neurol Dis 2011;8:1–9.\n'},{id:"B10",body:'\nPienaar PR, Micklesfield LK, Gill JMR, et al. Ethnic differences in microvascular function in apparently healthy South African men and women. Exp Physiol 2014;99:985–94.\n'},{id:"B11",body:'\nMalan L, Schutte AE, Malan NT, et al. Specific coping strategies of Africans during urbanization: comparing cardiovascular responses and perception of health data. Biol Psychol 2006;72:305–10.\n'},{id:"B12",body:'\nHamer M, Malan L. Psychophysiological risk markers of cardiovascular disease. In: Psychophysiological Biomarkers of Health. Special Edition. Neurosci Biobehav Rev 2010;35:76–83.\n'},{id:"B13",body:'\nDe Kock A, Malan L, Hamer M, Cockeran M, Malan NT. Defensive coping and renovascular disease risk—adrenal fatigue in a cohort of Africans and Caucasians: the SABPA study. Phys Behav 2015;147:213–19.\n'},{id:"B14",body:'\nde Kock A, Malan L, Hamer M, Malan NT. Defensive coping and subclinical vascular disease risk—associations with autonomic exhaustion in Africans and Caucasians: the SABPA study. Atherosclerosis 2012;225:438–43.\n'},{id:"B15",body:'\nHamer M, Malan L, Schutte AE, et al. Conventional and behavioral risk factors explain differences in sub-clinical vascular disease between black and Caucasian South Africans: the SABPA study. Atherosclerosis 2011;215:237–42.\n'},{id:"B16",body:'\nMashele N, Malan L, van Rooyen JM. et al. Blunted neuro-endocrine responses linking depressive symptoms and ECG left ventricular hypertrophy in black Africans: the SABPA study. Cardiovasc Endocrinol 2014;3:59–65.\n'},{id:"B17",body:'\nArmario A, Vallès A, Dal-Zotto S, et al. A single exposure to severe stressors causes long-term desensitisation of the physiological response to the homotypic stressor. Stress 2004;7:157–72.\n'},{id:"B18",body:'\nPetrowski K, Herold U, Joraschky P, Wittchen H, Kirschbaum C. A striking pattern of cortisol non-responsiveness to psychosocial stress in patients with panic disorder with concurrent normal cortisol awakening responses. Psychoneuroendocrinology 2010;35:414–21.\n'},{id:"B19",body:'\nBetito K, Diorio J, Meaney MJ, Boksa P. Adrenal phenylethanolamine N-methyltransferase induction in relation to glucocorticoid receptor dynamics: evidence that acute exposure to high cortisol levels is sufficient to induce the enzyme. J Neurochem 1992;58:1853–62.\n'},{id:"B20",body:'\nCiaranello RD. Regulation of phenylethanolamine N-methyltransferase. Biochem Pharmacol 1978;27:1895–97.\n'},{id:"B21",body:'\nHellhammer DH, Wüst S, Kudielka BM. Salivary cortisol as a marker in stress research. Psychoneuroendocrinology 2009;34:163–71.\n'},{id:"B22",body:'\nYoung EA, Altemus M. Puberty, ovarian steroids, and stress. Ann N Y Acad Sci 2004;1021:124–33.\n'},{id:"B23",body:'\nLichtman J, Froelicher ES, Blumenthal JA. et al. Depression as a risk factor for poor prognosis among patients with acute coronary syndrome: Systematic review and recommendations. A Scientific Statement from the American Heart Association. Circulation 2014;129:1350–69.\n'},{id:"B24",body:'\nMashele N, Malan L, Van Rooyen JM, et al. Depression, cardiometabolic function and left ventricular hypertrophy in African men and women: the SABPA study. J Clin Exp Hypertens 2013;35:213–19.\n'},{id:"B25",body:'\nBurke HM, Fernald LC, Gertler PJ, Adler NE. Depressive symptoms are associated with blunted cortisol stress responses in very low-income women. Psychosom Med 2005;67:211–16.\n'},{id:"B26",body:'\nBurke HM, Davis MC, Otte C, Mohr DC. Depression and cortisol stress response: a meta-analysis. Psychoneuroendocrinology 2005;30:846–56.\n'},{id:"B27",body:'\nPeeters F, Nicholson NA, Berkhof J. Cortisol responses to daily events in major depressive disorder. Psychosom Med 2003;65:836–41.\n'},{id:"B28",body:'\nGerra G, Zaimovic A, Mascetti GG, et al. Neuroendocrine responses to experimentally induced psychological stress in healthy humans. Psychoneuroendocrinology 2001;26:97–107.\n'},{id:"B29",body:'\nBergua M, Kapsreiter WL, Neuhuber HA et al. Innervation pattern of the preocular human central retinal artery. Exp Eye Res 2013;110:142–47.\n'},{id:"B30",body:'\nJensen RA, Shea S, Ranjit N. et al. Psychosocial risk factors and retinal microvascular signs. The Multi-Ethnic Study of Atherosclerosis. Am J Epidemiol 2010;171:522–31.\n'},{id:"B31",body:'\nSchlaich MP, Kaye DM, Lambert E, et al. Relation between cardiac sympathetic activity and hypertensive left ventricular hypertrophy. Circulation 2003;108:560–65.\n'},{id:"B32",body:'\nMalan L, Hamer, M, Frasure-Smith N. et al. COHORT PROFILE: Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) Prospective Cohort Study. Int J Epidemiol 2015;44:1814–1822.\n'},{id:"B33",body:'\nMalan NT, Stadler T, Schlaich MP, et al. Chronic distress and acute vascular responses associated with ambulatory blood pressure in low-testosterone African men: the SABPA study. J Hum Hypertens 2014;28:393–98.\n'},{id:"B34",body:'\nMosteller RD. Simplified calculation of body-surface area. N Eng J Med 1987;317:1098.\n'},{id:"B35",body:'\nKroenke K, Spitzer RL. The PHQ-9: a new depression diagnostic and severity measure. Psychiatr Ann 2002;32:1–7.\n'},{id:"B36",body:'\nMonahan PO, Shacham E, Reece M, et al. Validity/reliability of PHQ-9 and PHQ-2 depression scales among adults living with HIV/AIDS in Western Kenya. J Gen Intern Med 2009;24:189–97.\n'},{id:"B37",body:'\nKohara K, Nishida W, Maguchi M, Hiwida K. Autonomic nervous function in non-dipper essential hypertensive participants: evaluation by power spectral analysis of heart rate variability. Hypertension 1995;26:808–14.\n'},{id:"B38",body:'\nMancia G, Fagard R, Narkiewicz K, et al. ESH/ESC guidelines for the management of arterial hypertension. The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2013;31:1281–357.\n'},{id:"B39",body:'\nHayman DM, Xiao Y, Yao Q, et al. Alterations in pulse pressure affect artery function. Cell Mol Bioeng 2012;5:474484.\n'},{id:"B40",body:'\nKnudtson MD, Lee KE, Hubbard LD, et al. Revised formulas for summarizing retinal vessel diameters. Curr Eye Res 2003;27:143–49.\n'},{id:"B41",body:'\nBoomsma F, Alberts G, van Eijk L, et al. Optimum collection and storage conditions for catecholamine measurements in human plasma and urine. Clin Chem 1993;39:2503–08.\n'},{id:"B42",body:'\nNguyen TT, Wang JJ, Sharrett AR. et al. Relationship of retinal vascular caliber with diabetes and retinopathy. Diabetes Care 2008;31:544–49.\n'},{id:"B43",body:'\nIkram MK, Ong YT, Cheung CY, Wong TY. Retinal vascular caliber measurements: clinical significance, current knowledge and future perspectives. Ophthalmologia 2013; 229: 125–36.\n'},{id:"B44",body:'\nSchram MT, Chaturvedi N, Fuller JH, Stehouwer CD, EURODIAB Prospective Complications Study Group. Pulse pressure is associated with age and cardiovascular disease in type 1 diabetes: the Eurodiab Prospective Complications Study. J Hypertens 2003;21:2035–044.\n'},{id:"B45",body:'\nLiew G, Campbell S, Klein R, et al. Ten-year longitudinal changes in retinal microvascular lesions. The Atherosclerosis Risk in Communities Study. Ophthalmology 2011;118:1612–18.\n'},{id:"B46",body:'\nGrippo A, Johnson AK. Stress, depression and cardiovascular dysregulation: a review of neurobiological mechanisms and the integration of research from preclinical disease models. Stress 2009;12:1–21.\n'},{id:"B47",body:'\nOtte C, Neylan TC, Pipkin SS. et al. Depressive symptoms and 24-hour urinary norepinephrine excretion levels in patients with coronary disease: findings from the Heart and Soul Study. Am J Psychiatry 2005;162:2139–45.\n'},{id:"B48",body:'\nMalan L, Hamer M, Schlaich MP, et al. Facilitated defensive coping, silent ischemia and ECG left ventricular hypertrophy: the SABPA Study. J Hypertens 2012;30:543–50.\n'},{id:"B49",body:'\nYeung AC, Ganz P, Selwyn AP. Interactions between mental stress and coronary endothelial dysfunction. Homeostasis 1993;34:244–51.\n'},{id:"B50",body:'\nVan Lill AS, Malan L, van Rooyen JM, et al. Baroreceptor sensitivity and left ventricular hypertrophy in urban South African men: the SABPA study. Blood Pressure 2011;20:355–61.\n'},{id:"B51",body:'\nFeihl F, Liaudet L, Waeber B, Levy BI. Hypertension: a disease of the microcirculation. Hypertension 2006;48:1012–17.\n'},{id:"B52",body:'\nOpie LH. Heart Physiology—From Cell to Circulation, 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2004: 421 p.\n'},{id:"B53",body:'\nFlammer J. Psychophysical mechanisms and treatment of vasospastic disorders in normal-tension glaucoma. Bull Soc Belge Opthalmol 1992;244:129–34.\n'},{id:"B54",body:'\nSteinle JJ, Smith PG. Role of adrenergic receptors in vascular remodelling of the rat choroid. Brit J Pharmacol 2002;136:730–34.\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Nicolaas T. Malan",address:"nico.malan@nwu.ac.za",affiliation:'
Hypertension in Africa Research Team (HART), Faculty of Health Sciences, North West University, Potchefstroom, South Africa
'},{corresp:null,contributorFullName:"Roland von Känel",address:null,affiliation:'
Hypertension in Africa Research Team (HART), Faculty of Health Sciences, North West University, Potchefstroom, South Africa
Department of Psychosomatic Medicine, Clinic Barmelweid, Barmelweid, Switzerland
Autonomic and Neuroendocrinological Laboratory Dresden, Department of Neurology, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany
Hypertension in Africa Research Team (HART), Faculty of Health Sciences, North West University, Potchefstroom, South Africa
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1. Introduction
1.1 Traffic congestion: a challenging front
Recent decades have witnessed a rapid surge in population growth. Consequently, a high concentration of social and economic activities in urban metropolitans has led to the emergence of various transportation modes and services. Urban traffic congestion has become a daunting challenge in cities around the world. Excessive delay, low traveling speeds, increased travel costs, elevated drivers’ anxiety and frustrations, high fuel consumption, and vehicular emissions are the few consequences of traffic congestion. It also poses a threat to a stable urban economy [1, 2]. Traffic demands fluctuate significantly during the day (TOD), especially during rush hours, which is one of the main causes of congestion buildup. Congestion may be recurrent, arising from routine cyclic fluctuations in traffic volumes, or it may be non-recurrent produced due to unforeseen events such as traffic incidents, unpredictable weather conditions. Existing transport infrastructure cannot withstand the ever-growing traffic demands, while the inappropriate allocation of temporal and spatial resources further exacerbates the problems [3, 4]. An effective solution to mitigate traffic congestion is to embed intelligent transportation system (ITS) technologies in existing transport infrastructure for efficient and sustainable operations. Researchers and practitioners have proposed various strategies such as signal control optimization and dynamic lane grouping to address the issue in recent years.
1.2 Traffic signal control (TSC)
Signalized intersections are a vital component of urban traffic networks and play a pivotal role in traffic control and management strategies. Over the years, they have been the primary focus of traffic improvement efforts since they are representative of frequent and restrictive bottlenecks. Poor traffic management at urban intersections leads to traffic jams and unsustainable travel patterns network-wide. Alternatively, intelligent traffic control and better management at these critical locations could result in smooth, safe, cheap, and sustainable operations. Traffic Signal Control (TSC) is an integral part of ITS. TSC is an important operation that can tackle various urban traffic issues such as congestion, fuel consumption and exhaust emission, and inefficient resource utilization. TSC involves determining appropriate signal timings parameters to improve various traffic performance measures like average vehicle delay, travel time, maximizing throughput, and reducing queue lengths and vehicular emissions. One of the main objectives of traffic signal control is to facilitate the safe and efficient movement of people through a road network. Achieving this goal warrant establishment of an accommodation plan that ensures appropriate assignment of right-of-way (ROW) to different users.
1.3 Classical methods for TSC
Over the years, different strategies have been proposed to address the TSC problem. A fixed-time signal control scheme has been widely used for managing traffic lights in urban areas. This strategy requires the determination of optimum TOD breakpoints for establishing TOD intervals, which are subsequently used for obtaining the predefined green splits for each split (green times) using Webster’s formula or some other optimization tools [5]. However, the fixed-time signal control strategy is suitable for stable and nearly homogenous traffic patterns. Alternatively, studies have focused on actuated and traffic responsive TSC schemes for dynamic traffic control and management. In such traffic control schemes, signal cycle length and green splits are adjusted according to real-time traffic data collected from sensors installed on each approach. Though actuated TSC strategies overcome some limitations of the former methods, they do not work well under all traffic and adverse conditions. TSC problem was initially addressed using various probability and regression-based methods [6, 7]. However, for oversaturated and undersaturated traffic conditions, such methods do not provide reliable solutions. Few notable classic TSC strategies proposed during the last few decades include: SCOOT [8], SCAT [9], MAXBAND [10], CRONOS, PRODYN [11], TRANSYT [12], RHODES [13], OPAC [14], and FUZZY LOGIC [15]. Few other methods recently used for traffic light setting are ARRB [16], TRRL [8], and HCM [17]. In addition, to signal control strategies, traffic light design could be isolated intersection based or coordinated. Isolated intersections signal schemes have limited benefits compared to coordinated strategies that consider the network of intersections.
1.4 Limitations of classical TSC strategies
The timing of traffic signals significantly influences the performance of the transportation system. Obtaining the optimal signal timing plan for a network in its entirety is challenging due to the stochastic and non-linear characteristics of the traffic system. From a computational perspective, the signal control optimization problem under the influence of several constraints is a highly non-linear and non-convex problem. To reduce the complexity of problem, studies have assumed partial convexification for obtaining the optimal signal plans [18, 19]. It has been shown that traffic light optimization belongs to the family of NP-complete problems whose complexity increases dramatically for real-world and more extensive transportation networks with prolonged study periods. Classical optimization methods used in this regard are not suitable for a variety of reasons. For example, they are sensitive to initial estimates of solution vector and require gradient computation of constraints and the objective functions. Further, the discrete nature of signal timing plan and phasing sequence limit the application of traditional optimization approaches. Similarly, classical signal control optimization techniques are usually more suited to isolated intersections. They are not scalable for large urban transport networks where the interdependence of traffic signals across multiple intersections may be explored. Hence, such methods do not consider the interdependencies and connectivity of traffic signals vital for large-scale urban transport networks.
1.5 Metaheuristics for TSC: the new frontier
Metaheuristics techniques, including and swarm intelligence and evolutionary algorithms, have emerged as appealing alternatives to classical optimization methods for addressing signal control problems. They can be easily adapted for solving signal optimization problems with mixed types of continuous and discrete variables on large-scale transportation systems. Metaheuristics are based on approximate random methods and involve an iterative master process that can efficiently provide high-quality, acceptable solutions with relatively low computational efforts [20]. No prior information regarding the search space characteristics is required. In addition, metaheuristics do not rely on gradient information of the objective functions and the associated constraints with reference to signal timing variables. Further, the process of finding the optimal solution is simple and straightforward. Entailing less complexity than exact methods means that metaheuristics could be easily implemented to solve non-linear complex optimization problems. Furthermore, for many large-scale engineering problems that involve uncertainties (such as traffic flow), obtaining near-optimal solutions within a reasonable time is acceptable. Owing to these benefits, several metaheuristics techniques have been successfully applied for solving TSC optimization problems. Metaheuristics aim at obtaining the optimal values/ranges for various signal parameters that influence the performance of signalized intersections and include variables such as cycle length, green splits, phase sequence, offsets, change interval, etc. These parameters of interest are also known as decision variables. Constraints conditions for signal optimization include lower and upper cycle length, green splits thresholds, etc.
Metaheuristics have been widely applied to solve the TSC problems under a single objective framework known as mono-objective optimization. The single objective optimization can be classified into four main types: i) travel time minimization, ii) delay minimization, iii) throughput maximization, and iv) fuel consumption and exhaust emissions (CO, CO2, NOx, HCs) minimization. Mono-objective optimization of traffic signals has some benefits; however, field traffic is highly complex, non-linear, and stochastic in nature, and quite often, the application of multi-objective optimization becomes inevitable. In the process of finding the optimal signal control parameters, traffic engineers usually deal with multiple conflicting objectives. They are seldom interested in knowing the single-objective-based best solution without considering the other objectives. It is quite possible that an indented improvement in one of the objectives may lead to the deterioration of others. Therefore, it is essential to obtain a reasonable trade-off among various clashing objectives while optimizing the signal timing parameters. To address this issue, researchers have proposed bi-objective or multi-objective metaheuristic frameworks which involve more than one objective function to be optimized concurrently. Adoption of multi-criteria/objectives metaheuristics for signal optimization is rational as well as more beneficial.
1.6 Study objectives
This study provides a comprehensive review of metaheuristics techniques applied to signal control optimization. The surveyed literature is categorized based on the types of metaheuristics used, i.e., evolutionary algorithms and swarm intelligence techniques. A total of over 15 metaheuristics optimization techniques in traffic signal control and optimization are presented. Literature is summarized based on classification of techniques, considered optimization objectives, decision variables, and constraints conditions. Finally, based on the identified literature gaps, major challenges and prospects for future research are also proposed.
1.7 Paper organization
The remainder of this work is organized as follows. Section 2 provides research methods and publication analysis of signal control optimization using metaheuristics. Section 3 reviews evolutionary algorithms’ metaheuristics for signal optimization. Section 4 provides a summary of swarm intelligence techniques in the context of the subject domain. Section 5 and 6 presents surveys of trajectory-based metaheuristics and few others for TSC optimization. Finally, Section 7 presents the review conclusions and outlines the current challenges and recommendations for future research.
2. Methodology
The relevant literature on TSC was searched (in May 2021) using a detailed systematic review (SR). SR is a formal and standard protocol for performing a review study. To ensure that findings were reached in a valid and reliable manner, the study adopted a three-staged approach, i.e., i) planning, ii) execution, and iii) analysis. The planning stage involved defining the research scope and aims, setting the inclusion and exclusion criteria, and developing the review protocols. The execution stage involved a systematic search using relevant search strings. The relevant publications were meticulously selected by browsing through different electronic databases such as “Google Scholar,” Science Direct,” Wiley Online Library,” “Scopus,” “Web of Science,” and “IEEE Xplore.” To explore these databases, the following “Keywords” were used: “signalized intersections,” “traffic congestion,” “traffic signal control,” “traffic signal timing optimization,” “traffic control through metaheuristics,” “intelligent traffic control,” “dynamic traffic management,” “traffic simulation and optimization,” “multi-objective traffic control,” etc. Titles, keywords, and abstracts of all the downloaded documents were reviewed to determine the appropriate selection of articles for the current study. Additional appropriate publications were added to the list by looking at the references selected publications. Publications were searched irrespective of publication year and the number of citations to have the maximum number for initial consideration. Duplicate articles found in various databases were also identified and removed. Non-academic publications, such as magazine articles, company reports, newspapers, presentations, and interview transcripts, were excluded. Finally, the analysis stage involved the classification, categorization, and summarization of the main theme of selected articles.
Figure 1 presents the chronological distributions of shortlisted publications in which metaheuristics are used for solving traffic signal control optimization. It may be observed from the publications reporting in Figure 1 that is there is a growing trend in the application of metaheuristics in the subject domain. Figure 2 shows the percentage distribution of published studies in the area of traffic control optimization based on the type of metaheuristic applied. It may be observed from the Figure that the Genetic Algorithm (GA), Particle Swarm Optimization (PSO), and Ant Colony Optimization (ACO) have been widely used for signal optimization.
Figure 1.
Chronological distribution of indexed publications on traffic signal optimization using swarm intelligence and evolutionary computation techniques (period 2000–2021).
Figure 2.
Percentage distribution of indexed publications on traffic signal optimization based on metaheuristic type.
3. Review of evolutionary algorithms (EAs) for TSC
This section reviews the previous studies in the literature that applied evolutionary algorithms (EAs) for traffic signal control and optimization. EAs are the most widely used metaheuristics optimization techniques across diverse fields of science and engineering. EAs are population-based random search techniques and are inspired by Darwin’s theory of natural theory of evolution. The EAs contain a population of individuals, each symbolizing a search point in the feasible solution space exposed to a common learning process while proceeding among different generations. EAs begins with the initialization of random population, which are then subjected to selection, crossover, mutation through various generations so that offsprings generated evolve toward more favorable regions in the search space. At each generation, the fitness of the population is evaluated, and those with better fitness values are selected and recombined that have an increased probability of improved fitness. The program is iteratively repeated until it converges to the best (or near-optimal) solutions. The basic structure of EAs remains similar for all the algorithms under its family. Figure 3 presents the sample structure of EAs and their working principle. The following passages provide a brief explanation of various EAs employed in the field of traffic signal optimization. Table 1 presents a summary of previous studies that have applied EAs for traffic signal control and optimization.
Figure 3.
General flow depicting the search mechanism of EAs.
Summary of previous studies on traffic signal optimization using EAs.
3.1 Genetic algorithm
Genetic algorithm is the most widely used method for traffic light optimization. John Holland initially proposed the GA metaheuristic in 1975 [39]. GA search mechanism for finding the optimal solution of an objective function mimics the natural selection process of the evolutionary theory of nature, which supports the “survival of the fittest” concept. It is a population-based technique that involves the ranking of individual members of the population according to their fitness.
The search process of the optimal solution begins with the initialization of a random population of solutions. The offspring population is created by iteratively applying various genetic operators such as crossover, mutation, elitism, etc. until the stopping criteria are satisfied. In literature, many studies have demonstrated the robustness of GA for adaptive traffic signal control. For example, Foy et al. utilized GA for traffic light optimization, considering delay time minimization as the objective function [36]. The number of initial GA generations was varied over five GA traffic runs. The optimal fitness value was achieved for populations ranging between the 20th to 30th generations with an average vehicle waiting time of around 40 seconds. GA was noted to yield rational signal timing plans reducing the timing delay significantly compared to the existing traffic control scheme. In their study, Rahbari et al., studied that traffic control at the signalized intersection with GA could reduce the congestion [40]. Yang and Luo adopted a hybrid GA simulated annealing (GA-SA) for signal control optimization at isolated signalized intersections considering delay as the objective function [41]. Empirical results showed that GA produced a rational signal timing plan compared to fixed control scenarios. A study conducted by Mingwei et al. proposed the application of multi-objective for intelligent traffic management at an isolated signalized intersection for a case study in China [42]. The considered optimization objectives included; average vehicle delay, vehicular stops, and fuel consumption. It was found that the optimized signal timing plan from GA significantly improved the considered traffic performance measures.
In another study, Turki et al. proposed a multi-objective NSGA-II to optimize various measures of effectiveness (such as delay, stops, fuel consumption, and emissions) at isolated signalized intersections in the city of Dhahran, Saudi Arabia [35]. Study results were compared with Synchro traffic simulation and optimization tool, and the results for a typical intersection are shown in Figures 4 and 5. All the performance measures witnessed considerable improvement for the optimized signal timing plan obtained using an NSGA-II optimizer. Figure 4(a–d) depicts the evolution of the four selected performance measures (delay, stops, fuel consumption, and emissions) against the number of iterations for three random initial populations. It may be noted that all the algorithms converged to their respective objective functions at approximately 70 to 100 generations. Comparing the random initial populations, population size 30 for all cases yielded the best results.
Figure 4.
Evolution of different performance measures against NSGA-II iterations; (a) delay evolution, (b) number of vehicle stops evolution, (c) fuel consumption evolution, (d) emission evolution. Reprinted with permission from Ref. [35] copyright (2021), MDPI.
Figure 5.
Comparison of NSGA-II and synchro optimizers for various traffic performance measures. Reprinted with permission from Ref. [35] copyright (2021), MDPI.
Figure 5 shows the performance comparison of NSGA-II and Synchro signal control strategies for the selected measures of effectiveness (delay, stops, fuel consumption, and emissions). It may be noted from the Figure that the NSGA-II optimizer outperformed the Synchro results for all the performance measures.
Li et al. also investigated the applicability of NSGA-II for solving signal control optimization problems [34]. Average queue ratio and vehicle throughput were the objective functions. The algorithm’s results were validated on a microscopic traffic simulation tool, VISSIM. Kwak et al. developed a GA traffic optimizer to evaluate the influence of traffic light setting on vehicle fuel consumption and emissions [32]. Model results were compared with TRANSIM, a microscopic traffic simulator. It was observed that the proposed GA traffic optimizer could reduce exhaust emissions by approximately 20% and fuel consumption in the range of 8–20%. In another study, Kou et al. employed multi-criteria GA for optimizing the signal timing plan of signalized junctions and compared the results with the highway capacity manual (HCM) method [28]. The study considered several optimization objectives such as stops, delays, and emissions. A reasonable trade-off established an optimal Pareto front among different conflicting objectives. Study results demonstrated the superior performance of the proposed GA traffic control scheme compared to the HCM method in terms of all the optimization objectives. Guo et al. developed a model for area-wide intersection traffic control in the central business district (CBD) area of Nanjing, China [43]. Capacity ratio, turning movement delay, and travel time was the three chosen objective functions. Computational experiments results showed significant mobility improvement compared to existing conditions. Study results were also validated in PARAMICS traffic simulation tool. In their study, Dezani et al. have shown that simultaneous optimization of traffic lights via GA and vehicle routes could significantly reduce the vehicle travel time compared to optimization considering only routes [44]. In another study, Tan et al. proposed a new Decentralized Genetic Algorithm (DGA) for signal timing optimization of traffic networks under oversaturated traffic conditions [45]. Average vehicle delay was used as the performance metric to evalauate the performance of proposed algorithm. Simulation results showed that DGA could effectively optimize the traffic light setting and reduced the average network delay.
3.2 Differential evolution (DE)
Differential evolution is another population-based metaheuristic technique initially proposed by K.V. Pricein 1995 [46]. DE is characterized by its robustness, fast convergence to the objective function, and simplicity. Though the method has been successfully used for numerous applications across different disciplines, only a few studies have adopted DE for urban traffic control and management [25, 26, 27, 28, 29]. For example, in their recent study, Jamal et al. compared the performance of GA and DE for optimizing traffic lights at isolated signalized intersections in the city of Dhahran, Saudi Arabia [29]. Average delay time minimization was the objective function. The study concluded that both GA and DE could yield intelligent and rational signal timing plans, reducing the intersection average delay between 15 and 35%. DE was noted to converge to objective function faster than DA over several simulation runs. Similarly, in another study, Liu et al. proposed bacterial foraging optimization-based DE algorithm for optimizing delay at signalized intersections [37]. To improve convergence precision, DE was utilized for updating the bacteria position during the chemotaxis process. The proposed scheme yielded very promising results, reducing the intersection delay by over 28% compared to only 5% obtained by GA optimization. In their study, Korkmaz et al. suggested three different types of delay differential evolution-based delay estimation models (DEDEM), i.e., linear, quadratic, and exponential [47]. The researchers reported that all the proposed models effectively predicted the vehicle delay estimates in terms of relative errors between estimated and simulated values; however, quadratic DEDEM methods outperformed other models. Ceylan also approached the signal control optimization problem using the metaheuristic DE and Harmony-Search (HS) for network-wide traffic control and optimization [48]. Study results showed that DE algorithms yielded better results compared to HS.
In another research study, Yunrui et al. proposed multi-agent fuzzy logic control based on DE to optimize delay and queue length through a network of eleven intersections in the urban traffic context [31]. DE was used to decide and optimize the parameters of the fuzzy systems because it is easy to understand and implement. Empirical results revealed that the proposed method could substantially improve the network performance measures such as average vehicle delay, traffic throughput, and queue length. In a recent study, Liu et al. have proposed an improved adaptive differential evolution (ADE)-based evolvable traffic signal control (EvoTSC) scheme for global optimization of different traffic performance measures on large scale urban transportation networks [49]. The proposed TSC method was compared with a conventional TSC scheme on two practical and three synthetic transportation networks with varying traffic flow demands and different physical scales. Comparison results indicated that the DE-based EvoTSC method significantly outperformed its counterpart under all the considered scenarios. Zhang et al. also applied an online intelligent urban traffic signal control approach using multi-objective DE for real-time traffic control and optimization [50]. Experimental results showed that the proposed approach provides a more robust configuration of traffic signal phases and has relatively better real-time performance than the traditional traffic control scheme.
3.3 Genetic programming (GP)
Genetic programming (GP) is another population-based metaheuristic technique that belongs to the family of evolutionary algorithms [51]. GP is an extension of GAs that allows for deep exploration of space on computer programs. GP starts with a population of random programs (candidate solutions) that are fit for applying evolutionary operators similar to genetic processes, thereby simulating the fundamental principles of Darwin’s evolution theory [52]. GP follows an iterative process to breed the solutions to problems using the probabilistic selection procedure for the carryover of fittest solutions to the offerings by applying genetic operators such as crossover and mutation. In literature, not many studies have focused on applications of GP for traffic analysis and management in urban transport networks. Montana and Czerwinski used a hybrid GA with strongly typed GP (STGP) for intelligent control and optimization of evolving traffic signals on a small-scale transport network [53]. Numerical simulation results showed that the proposed hybrid STGP model could effectively improve network performance under varying traffic demands.
A study conducted by González also proposed the application of GP for solving signal control problems [54]. This study considered four different traffic scenarios with properties and traffic conditions in a previous study [55]. Study results were also validated using the microscopic traffic simulator tool SUMO. Findings showed that GP could provide competitive and robust results for all the tested scenarios. However, the highway/network scenario had a more pronounced performance improvement (having an improvement of 10.34%) than the isolated intersection scenario (with an improvement of 4.24%). In another study, Ricalde and Banzhaf adopted an improved GP with epigenetic modifications for traffic light scheduling and optimization under dynamic traffic conditions [56]. Extensive simulation analysis revealed that the proposed model improved the network performance compared to standard GP and other previously used methods. This study, however, did not use any real-world data for validation purposes. In another study, the authors used a similar GP approach with epigenetic modifications (EpiGP) to design and evolve traffic signals using real-time field traffic data [38]. Results indicated significant improvement in network performance compared to conventional methods, including standard GP, static, and actuated traffic control techniques. Over 12% improvement in average delay was reported under high-density traffic conditions.
4. Review of swarm intelligence (SI) techniques for TSC
This section reviews the previous studies in the literature that applied swarm intelligence (SIs) techniques for traffic signal control and optimization. SI is another class metaheuristics that are increasingly used for various engineering and industrial applications. The search mechanisms of SI are believed to be inspired by human cognition representing the individual’s interaction in a social environment. For this reason, SI techniques are also sometimes called “behaviorally inspired algorithms.” In SI algorithms, each swarm member has a stochastic behavior due to their perception of the neighborhood and acts without supervision. By collective group intelligence, swarm utilizes their resources and environment effectively. The primary attribute of a swarm system is self-organization, which assists in evolving and obtaining the desired global level response by effective interactions at the local level. Just like EAs, SIs are population-based iterative procedures. After randomly initializing the population, individuals are evolved across different generations by mimicking the social behavior of animals or insects to reach the optimal solutions. However, SIs do not involve the use of evolutionary operators like crossover and mutation like EAs. Instead, a potential solution modifies itself based on its relationship with the environment and other individuals in the population as it flies through the search space. The following passages provide a brief explanation of various swarm intelligence techniques employed for solving signal control optimization problems. Table 2 presents a summary of previous studies that have applied SIs for traffic signal control and optimization.
Summary of previous studies on traffic signal optimization using SI techniques.
4.1 Particle swarm optimization (PSO)
Particle swarm optimization is a population-based swarm intelligence technique that was first introduced in 1995 by Eberhart and Kennedy. In the PSO algorithm, every potential solution is referred to as a particle representing a location in the problem space. The entire population of potential solutions (particles) is called the swarm. PSO search mechanism for global optima is inspired by birds in which each particle can update its velocity and position by using local and global best values. PSO is yet another widely used optimization algorithm for signal control problems. For example, Celtek applied PSO for real-time traffic control and management in the city of Kilis city in Turkey [77]. Algorithm performance was investigated in real-time using the SUMO traffic simulator. Social Learning-PSO was introduced as an optimizer for the traffic light. Empirical results obtained using the proposed PSO architecture resulted in travel time by 28%. The algorithms performed well both for undersaturated and oversaturated traffic conditions. Gokcxe and Isxık proposed a microscopic traffic simulator VISSIM-based PSO model for optimizing vehicle delay and traffic throughput using field data from28 signalized roundabout in Izmir, Turkey [64]. The simulation tool was used to evaluate the solutions obtained by PSO. Optimization of traffic signal head reduced the average delay time per vehicle by approximately 56% and increased the number of passing vehicles by 9.3%. In their study, Jia et al. employed multi-objective optimization of TSC using PSO [72]. The optimization objectives included average vehicle delay, traffic capacity, and vehicle exhaust emissions. The validity of the algorithm was examined by applying it to the real-time signal timing problem. The suggested algorithm provided competitive performance for all the MOEs compared to other efficient algorithms such as NSGA-II, IPSO, and GADST.
Abushehab et al. compared PSO and GA techniques for signal control optimization on a network of 13 traffic lights [78]. SUMO was used as a simulator tool for the network. Both the algorithms yielded systematic and rational signal timing plans; however, some algorithm variants were found to be more efficient than the others. In their study, Angraeni et al. proposed a modified PSO (MSPO) and fuzzy neural network (FNN) for optimizing signal cycle length at an isolated intersection [79]. Simulation results using PSO led to a reduction in MSE value from 6.3299 to 2.065, while network performance was improved by 4.26%. The accuracy of the training process using MPSO was higher than FNN. Chuo et al. reported a significant decrease in vehicle queue length by using PSO as a traffic signal optimizer [73]. In another study, Garcıa-Nieto et al. applied PSO to optimize the cycle program of 126 traffic signals located in two large and heterogenous metropolitans of cities of Bahıa Blanca in Argentina and Malaga in Spain [80]. The Obtained solutions were validated using the traffic simulation package SUMO.
In comparison to the existing pre-defined traffic control schemes, PSO achieved significant quantitative improvement for both the objectives, i.e., overall journey time (74% improvement) and the number of vehicles reaching their destinations (31.66%) improvement). In another study, a researcher proposed an improved PSO architecture by combining traditional PSO with GA for multi-objective traffic light optimization. The selected performance indexes included vehicular emissions, vehicle delay, and queue length [40]. The authors reported that the improved PSO method has a quick response and higher self-organization ability which is beneficial for improving the efficiency of traffic signal control.
Olivera et al. investigated the applicability of PSO to reduce vehicular exhaust emissions (CO and NOx) and fuel consumption considering large-scale heterogeneous urban scenarios in the cities of Seville and Malaga in Spain [67]. Study results showed that the proposed signal control strategy could significantly reduce the exhaust emission (CO by 3.3% and NOx by29.3%) compared and fuel consumption (by 18.2%) compared to signals designed by human experts. In their study, Qian et al. designed a simulation protocol for traffic different signal parameters such as cycle, green signal ratio, and phase difference using three Swarms Cooperative-PSO algorithms [74]. The considered optimization objectives included average vehicle delay and average parking number per vehicle. Algorithm simulation results were validated using traffic simulator CORSIM. Lo and Tung compared the performance of PSO and GA-based signal control along four intersections on an urban arterial and noted that the PSO algorithm outperformed GA both in terms of speed convergence and accuracy of search [81]. A couple of other recent studies also demonstrated the adequacy and robust performance of PSO for TSC and optimization [82, 83].
4.2 Ant colony optimization (ACO)
Ant Colony optimization is a swarm intelligence method-based optimization technique that mimics the natural behavior of ants in finding the shortest path from an origin to a food source [84]. In ACO, the path of every ant from origin to destination is considered as a possible solution. ACO has been widely used for traffic signal optimization. In their study, Putha et al. used ACO for traffic signal coordination and optimization in the context of an oversaturated urban transport network [85]. The authors reported that ACO could provide reliable solutions of optimal signal timing plan compared to GA. Yu et al. also applied ACO for intelligent traffic control at signalized intersections considering vehicle waiting time as the optimization objective [86]. The authors reported that ACO outperformed the traditional traffic actuated scheme, predominantly during traffic flow periods. He and Hou also proposed the application of a multi-objective ACO algorithm for the timing optimization of traffic signals [57]. Several parameters such as vehicle delay, number of stops, and traffic capacity performance indices were chosen as performance indexes. Numerical simulation results demonstrated that ACO is a simple and robust technique for signal control optimization problems. The proposed ACO technique significantly improved the selected performance indicators compared to Webstar and GA algorithms.
In another study, ACO optimized the timing plan for traffic lights at isolated signalized intersections [61]. All the selected intersection measures of effectiveness (MOEs), including vehicle delay, parking rate, and the number of stops, were improved by a fair margin. Sankar and Chandra proposed a multi-agent ACO for effective traffic management on a network level [69]. The authors concluded that the method could be pretty useful in reducing average vehicle delays and traffic congestion under varying traffic conditions. Haldenbilen et al. developed an ACO-based TRANSYT (ACOTRANS) model for area traffic control (ATC) through a coordinated signalized intersection networks under different traffic demands [87]. A total of 23 links were considered for the analysis, and the network Disutility Index (DI) was chosen as the primary performance index. A comparative analysis of the network’s PI obtained using TRANSYT-7F with hill-climbing (HC) optimization and TRANSYT-7F with GA was also performed. Study results showed that the proposed ACOTRANS improved the network’s PI by 13.9% and 11.7% compared to its counterparts TRANSYT-7F optimization with HC and GA. Li et al. compared ACO and Fuzzy Logic for optimizing traffic signal timing in a simulated environment [88]. Traffic capacity and vehicular delay were considered as the objective functions and did not consider pedestrian traffic. The validity of proposed algorithms was tested using actual time-period and conventional algorithms. Jabbarpour et al. conducted a detailed review of the literature focused on applying ACO evolutionary algorithms for the optimization of vehicular traffic systems [90].
Rida et al. proposed ACO for real-time traffic light optimization problems at isolated signalized intersections [71]. Objective functions include minimizing the vehicle waiting time and increasing the traffic flow. The proposed model yielded robust performance compared to fixed time signal controller and other dynamic signal control strategies. Renfrew and Yu, in their studies, also reported that ACO demonstrated robust performance compared to actuated control in optimizing signal timing plan, particularly under high traffic demand [89, 91]. Srivastava and Sahana proposed a novel hybrid nested ACO model intending to reduce the vehicle waiting time at signalized intersections [92]. The proposed model was also compared with the hybrid nested GA model. Results showed that nested hybrid models outperformed traditional ACO and GA-based traffic control.
4.3 Artificial bee colony (ABC)
The traditional algorithms used for training carry some drawbacks of getting stuck in computational complexity and local minima. The artificial bee colony (ABC) algorithm is a revolutionary approach developed by Karaboga et al. [93]. ABC has good exploration capabilities in finding optimal weights during the training process [94]. ABC algorithm operates on the principle of foraging behavior of honeybees in seeking quality food. Each cycle of the search comprising three steps: sending employed bees onto the food source to measure nectar amount; selecting food source by onlookers once the information is shared by employed bees, and sending the scouts for discovering new food source [95].
ABC algorithm is widely used in optimizing traffic-related problems by previous researchers [60, 68, 96]. Zhao et al. investigated a typical intersection as a case study at Lanzhou city [60]. The green time length of each phase of the signal cycle and signal cycle were considered as decision variables. Favorable convergence was achieved using different setting parameters of the algorithm. The effect of signal cycle on control targets resulted that vehicle delays will increase with the signal cycle; however, the stops will decrease. In comparison to non-dominating sorting genetic algorithm and webster timing algorithm, ABC manifested better convergence. In another study, Dell’Orco et al. developed TRANSYT-7F to investigate network performance index (PI) for optimizing signal timing [96]. Results revealed that PI’s of the network in the case of ABC improved by 2.4 and 2.7% compared to genetic algorithm and hill-climbing method.
4.4 Cuckoo search (CS)
Cuckoo search (CS) is a recently developed metaheuristic algorithm developed by Yang and Deb [97], inspired by the natural breed parasitism of the cuckoo species. For understanding its working principle, consider that each bird lays one egg at a time and dumps it in a random nest which represents a single solution. The nest with high-quality eggs will be moved to the next generation. The number of host nests is fixed, and the egg laid by the cuckoo is discovered by the host bird. In this situation, the host bird either gets rid of the egg or abandons the nest by developing a new nest [98]. Few studies interpret CS as more efficient than PSO and GA [97].
Araghi et al. employed neural networks (NN) and adaptive neuro-fuzzy inference system (ANFIS) to optimize the results of CS in the case of intelligent traffic control [63]. The results were compared to that of the fixed time controller. It was revealed that the CS-NN and SC-ANFIS showed 44% and 39% improved performance against the fixed-time controller. Similarly, in another study, the authors evaluated the performance of ANFIS using CS for optimization of controlling traffic signals for an isolated intersection [70]. Improved performance of ANFIS-CS was obtained against fixed-time controller.
4.5 Bat algorithm (BA)
Bat algorithm (BA), initially developed by Xin-she yang in 2010, is inspired by the echolocation of microbats [99]. The working principle of BA encompasses three basic steps: bats use echolocation to sense the distance bifurcating the food and barrier; bats randomly fly with variable loudness and wavelength.; bats automatically adjust their wavelength and pulse depending upon the proximity of food/prey [100].
Srivastava, Sahana used BA to determine the wait time at a traffic signal for the discrete microscopic model [66]. The study was based on 12 nodes and four intersections. The results were compared to GA. Relatively higher performance was obtained for BA algorithm as compared to GA. Jintamuttha et al. carried experimental simulation for the green time of intersection for ten cycles per run [62]. The results of the experiment were optimized using BA. The average queue length and waiting time improved due to optimization.
4.6 Artificial immune system (AIS)/immune network algorithm (INA)
The immune network algorithm (INA) or artificial immune system (AIS) is another useful optimization algorithm recently practiced for signal control optimization problems. As its name suggests, the working mechanism of this algorithm is inspired by the biological immune system. Immune cells have receptors that can detect harmful pathogens and activate antibodies to fight them, leading to their elimination [101]. Louati et al. applied INA to optimize queue, delay, and traffic throughput at signalized intersections under varying traffic demands [75]. It was found that INA outperformed traditional fixed-time adaptive traffic control strategies and validated the study results through VISSIM, a microscopic traffic simulation platform. In another study, Trabelsi et al. evaluated the performance of AIS to detect and rationally control anomalous traffic conditions through a network of signalized intersections [58]. Simulation results proved the adequacy and robustness of the proposed AIS-based signal control method.
Darmoul et al. employed multi-agent immune network (INAMAS) for optimal control and management of interrupted traffic flow at signalized intersections [102]. The proposed INAMAS models offered an intelligent mechanism that could explicitly capture the disturbance-related knowledge of traffic fluctuations. To demonstrate the efficacy of the proposed model, the authors compared its performance against two widely used signal control strategies, namely fixed-time control and LQF-MWM (longest queue first –maximal weight matching) algorithm. The suggested INAMAS scheme provided a competitive performance in terms of chosen performance indicators, i.e., vehicle queue and waiting times under extreme traffic conditions involving high traffic volume and block approaches. Figure 6a plots the average vehicle delay for all the three signal control strategies under various traffic scenarios [102]. For scenario 1 (moderate traffic congestion), the INAMAS algorithm produces approximately a 24% reduction in average delay values compared to the LQF-MWM strategy. For scenario 2 (high-density traffic), the proposed INAMAS optimizer decreased the average delay by nearly 32%. For scenario 3 (extreme congestion), the corresponding improvement by the INAMAS algorithm is about 28%. Figure 6b depicts the relationship between the total network delay and simulation time (in minutes) for all three signal optimization strategies [102]. It is evident from the results in Figure 6b that during the first 5 minutes, all the controllers have comparable performance. At the end of simulation analysis (after 5 hours), when the traffic density reaches 9600 vehicles per hour, the INAMAS controller achieved better performance compared to others, showing its superior capability to manage large and complex traffic networks.
Figure 6.
(a) Comparison of average total delay per vehicle from various optimizers (b) cumulative network delay for scenario 1 for various optimizers Ref. [102].
Moalla et al., in their study, also demonstrated the robustness of AIS for controlling traffic at isolated signalized intersections [103]. However, the authors also emphasized that validation of the proposed AIS scheme is challenging and should be handled carefully. In another study, the author highlighted AIS-based traffic control’s significance for network-wide traffic management [104]. Comparative results with TRANSYT 7F showed the superior performance of AIS approach. Galvan-Correa et al. proposed a new metaheuristic known as the micro artificial immune systems (MAIS) to optimize vehicular emission and traffic flow in the city of Mexico [105]. The performance of the suggested MAIS technique was compared with several other metaheuristics, including GA, DE, SA, PSO. Results showed that MAIS achieved better results compared to most of the other metaheuristics. In a recent study, Qiao et al. proposed a novel hybrid algorithm, known as the Immune-Fireworks algorithm (IM-FWA) for effective traffic management on large-scale urban transportation networks [106]. The proposed hybrid algorithm was developed based on fireworks and artificial immune algorithms. A hierarchical strategy was proposed in the framework to avoid possible offsets conflicts and reasonable configuration of intersection offsets. Simulation results showed that the proposed IM-FWA could successfully overcome the shortcomings of FWA and AIS algorithms by providing a better and more rational signal timing plan to effectively reduce traffic flow delays.
4.7 Firefly algorithm (FA)
The characteristic behavior of fireflies is animated by Yang [107] into a nature-inspired meta-heuristic swarm intelligent method called Bat Algorithm. In BA, all fireflies are assumed unisex, and attractiveness is proportional to their brightness, which in turn depends on the distance. Thus, the brightness can be considered a cost function, which is maximized in optimization.
Kwiecień, Filipowicz [studied optimizing costs controlled by queue capacity, maximal wait, and servers [76]. It was deduced that the use of FA could maximize the value of the objective function, and FA converges toward the optimal solution very quickly. Goudarzi et al. [108] investigated traffic flow volume by a probabilistic neural network method called deep belief network (DBN). FA was used to optimize the learning parameters of DBN. As a result, the proposed model predicted the traffic flow with higher accuracy compared to traditional models.
4.8 Gray wolf optimizer (GWO)
Gray wolf optimizer (GWO) is a new metaheuristic technique recently proposed by Mirjalili in 2014 [109]. GWO is inspired by the social hierarchy and hunting behavior of gray wolves. In GWO optimization, the wolves represent a solution set of candidate solutions. The hunting cycle in the GWO commences with the acquisition of a random population of candidate solutions (wolves) followed by identifying optimal prey’s locations using a cyclic process. GWO has several advantages compared with evolutionary approaches, easy programming and implementation, algorithm simplicity, no need for algorithm-specific parameters, and lower computational complexity [110]. In recent years, GWO has been increasingly used in diverse disciplines. However, studies on its applications in transportation and traffic engineering in general and traffic control and optimization in particular are very few.
Teng et al. were the first to use a hybrid gray wolf and grasshopper algorithm (GWGHA) algorithm for timing optimization of traffic lights [111]. The obtained solutions were simulated in a microscopic traffic simulator package SUMO. The performance of the proposed GWGHA hybrid algorithm was compared with other metaheuristics like GWO, GOA, PSO, and SPSO2011. Results indicated that the proposed hybrid algorithm provided better solutions than its counterparts because it utilizes the feature of GWO for accelerating the convergence speed while using GOA to diversify the population. In another recent study, Sabry and Kaittan proposed a novel hybrid algorithm consisting of gray wolf and fuzzy proportional-integral (GW-FPI) for active vehicle queue management in an urban context [59]. The proposed traffic controller was compared with PI through repeated MATLAB simulations. Study results indicated the stable and robust performance of the proposed hybrid controller for queue management in a dynamic transport network with varying traffic flow demands.
5. Review of trajectory-based metaheuristics for TSC
This section surveys the previous works that applied trajectory-based metaheuristics techniques) for traffic signal control and optimization. As the name suggests, these algorithms form search trajectories in solution space and iteratively improve the single solution in its neighborhood. Their exploration process starts from a random initial solution generated by another algorithm. At each stage, the current solution is replaced by a better offspring population. Trajector-based metaheuristics are mainly characterized by their internal memory sorting the state of search, candidate solution generator, and selection policy for candidate movement through generations. Table 3 summarizes the previous works that applied trajectory-based search metaheuristics, hybrid metaheuristics, and others for traffic signal control and optimization.
Summary of previous studies on traffic signal optimization using trajectory-based metaheuristics, hybrid metaheuristics, and others.
5.1 Tabu search for signal control optimization
Tabu Search (TS) is a metaheuristic introduced by Fred Glover in 1986 to overcome the local search (LS) problem of existing methods [123]. TS allows the LS heuristic to diversify the search for solution space outside the local optima [124]. One of the important features of TS is its memory function, which can restrict few search directions for a more detailed LS, thereby making it easier to avoid local optimum solutions. By combining the greedy concept and randomization, the TS algorithm could provide an efficient solution to many optimization problems. In literature, only a few studies have focused on the application of Tabu search for signal control optimization. Hu and Chen proposed traffic signal control based on a novel greedy randomized tabu search (GRTS) algorithm considering travel time as the primary optimization objective [118]. GRTS results were compared with a GA-based traffic control scheme using data from a real city network to demonstrate the benefits of the proposed method. Numerical simulation results revealed that over 25% reduction in travel time might be achieved under medium to high traffic demands. In another study, Karoonsoontawong and Woller applied reactive tabu search (RTS) for simultaneous solutions of traffic signal optimization and dynamic user equilibrium problems on two transport networks in a simulated environment [119]. Three different variants of RTS were investigated based on deterministic or probabilistic neighborhood definitions. The performance of all the RTS variants was evaluated using three criteria such as solution quality, CPU time, and convergence speed. Simulation results showed that the RTS approach could provide promising results in terms of improving the overall network performance.
In a recent study, Hao et al. proposed a hybrid tabu search-artificial bee colony (TS-ABC) algorithm for robust optimization of signal control parameters in undersaturated traffic conditions at isolated signalized intersections [68]. This study considered two performance indexes such as average delay and mean-square error of average delay. The proposed signal control optimizer was validated using field data from an intersection in the city of Zhangye, China. Numerical simulation results compared with GA showed that the proposed TS-ABC is better in reducing the traffic delay under varying and heterogeneous traffic conditions. Chentoufi and Ellaia also proposed a hybrid particle swarm and tabu search (PSO-TS) for adaptive traffic lights timing optimization on real-time isolated signalized intersections in the context of Moroccan cities [120]. The authors also highlighted the significance of integrating the proposed PSO-TS model and VISSIM to achieve optimum average delay estimates. Simulation results demonstrated the superior efficiency of the PSO-TS technique against the traditional static models under oversaturated traffic conditions.
5.2 Simulated annealing (SA)
Simulated Annealing (SA), developed by Kirkpatrick et al. is inspired by the statistical mechanics of annealing in solids [125]. For understanding, consider a change in temperature, which causes a change in energy and movement of particles in solids. There is a sequence of decreasing temperature in annealing until criteria are met [126].
Li, Schonfeld [112] reported traffic signal time optimization using metaheuristic capabilities of SA with GA. It was concluded that SA-GA models outperform in optimization compared to individual SA and GA models. Similar results were reported by Song et al. in evaluating the optimized model for reducing traffic emissions on arterial roads [113]. Oda et al. [114] employed SA to optimize traffic signal timing and reported its improved performance as compared to traditional models.
6. Other metaheuristics for TSC
This section reviews the previous works that applied some other metaheuristics for traffic signal control and optimization. These include the harmony search algorithm, water cycle algorithm, and Jaya algorithm. Table 3 summarizes the previous works that applied trajectory-based search metaheuristics, hybrid metaheuristics, and others for traffic signal control and optimization.
6.1 Harmony search (HS)
The metaheuristic harmony search (HS) algorithm simulates the natural musical improvisation process where the musicians aim to achieve a near-perfect state of harmony [127]. In the HS algorithm, the candidate solution population is known as harmony memory (HM), where every single solution in solution space is referred to as “harmony,” which belongs to the “n”-dimensional vector. Though HS has been successfully used for numerous applications across diverse domains, its applications for signal control optimization are limited. In a recent study, Gao et al. applied to HS in addition to four others metaheuristics for traffic signal scheduling (TSS) problems [121]. Experiments were conducted on real-time data from signalized intersections in Singapore to examine the performance of proposed metaheuristics. The authors considered heterogeneous traffic conditions. Simulation results proved the adequacy of all algorithms; however, the hybrid algorithm (ABC-LS) outperformed other techniques in terms of solution quality.
In another study, Ceylan and Ceylan adopted a hybrid harmony search algorithm and TRANSYT hill-climbing algorithm (HSHC-TRANS) for solving stochastic equilibrium network design (SEQND) in the context of optimal traffic signal setting problems [128]. The effectiveness of HSHC-TRANS was evaluated against HS and GA in terms of network performance index (PI). Results showed that the proposed hybrid model yielded about 11% in the network’s PI compared to the GA-based model. In another study, Gao et al. addressed the urban traffic signal scheduling problem (TSSP) using a discrete harmony search (DHS) with an ensemble of local search [115]. The primary objective was to minimize the network-wide total delay under a pre-defined finite horizon. Extensive simulation experiments were carried out using traffic data from a partial transport network in Singapore. Comparative analysis showed that the HS algorithm as a meta-heuristic achieved better performance compared to fixed-cycle traffic signal control (FCSC). Dellorco et al. also investigated the applicability of HS for signal control optimization on the two-junction network with the fixed flow on the links [116]. A comparative analysis of HS with GA and HC algorithms showed that HS resulted in a better network’s PI compared to its counterparts. Afterward, the validity of the proposed HS algorithm was assessed by applying it to a test network.
6.2 Jaya algorithm
The Jaya algorithm is a recently proposed metaheuristic initially introduced by R.V. Rao [129]. The word Jaya comes from Sanskrit, which means “victory.” In the Jaya algorithm, the search strategy always attempts to be victorious by reaching the optimal and best solution, and thus it is named “Jaya.” It is arguably one of the simplest and easy-to-implement metaheuristics. The main benefit of Jaya for optimization problems lies in the fact that this algorithm requires only common controlling parameters such as population size and the number of iterations and does not require any additional algorithm-specific constraints/parameters. While this algorithm has been successfully used for several scheduling and optimization problems in recent years, its applications in the domain of traffic scheduling and management are relatively scarce.
A recent study conducted by Gao et al. compared the performance of Jaya algorithms with other metaheuristics (like water cycle algorithm (WCO), genetic algorithm (GA), artificial bee colony, and harmony search (HS), and hybrid ABC-LS) for solving traffic light scheduling problem [121]. Simulation results showed all the algorithms achieved competitive results; however, the hybrid algorithm attained better accuracy and convergence. The proposed models were also tested on real-time traffic and phase data from a network of intersections in the Jurong area of Singapore. In another study, the authors proposed an improved Jaya algorithm for solving traffic light optimization problems in the context of large-scale urban transport networks [122]. The chosen performance index was to minimize the network-wide total traffic delay within a given time horizon. To enhance the search performance in the local search space, a neighborhood search operator was proposed. Experiments were carried out using traffic data for a case study from the Singapore transport network. Study results demonstrated the robustness and better performance of proposed improved Jaya algorithms against standard Jaya algorithm and exiting traffic light control scheme. In another follow-up study, Gao et al. studied large-scale urban traffic lights scheduling problems using three different metaheuristics, namely Jaya, WCO, and HS [117]. The objective function was to optimize the delay time of all vehicles network-wise under a fixed time horizon. This study also proposed a feature search operator (FSO) to improve the search performance of proposed metaheuristics. To examine the efficacy of proposed methods, experiments were carried out using real-time traffic data. It was concluded that metaheuristic-based traffic control could significantly improve the network performance compared to existing traffic control strategies. Numerical simulation results showed that in comparison to feature-based search (FBS), operator for all algorithms improved the total vehicle delay time by more than 26% in their worst case scenarios.
Figure 7a depicts the relationships between total network delay time (sec) and sampling intervals for a typical urban traffic network with 100 junctions from the west Jurong area in Singapore [117]. Minimum (min.), average (avg.) and maximum (max.) total delay values each for 30 repeats and five sampling intervals (5, 10, 15, 20, and 30 sec) are reported. It is evident from the results that a sampling period of 15 seconds yielded the best results, which were then adopted for subsequent experiments. Figure 7b shows the relative percentage improvement in network performance (reduction in network delay) for standard Jaya algorithm with improved Jaya (iJaya), and Jaya with FBS operator (iJaya+FBS) for a sample 11 cases of traffic network from the same study [117]. Compared to standard Jaya, the iJaya yielded the improvements in range for 0–6% for min., avg., and max. Results, while iJaya+FBS algorithm resulted in corresponding improvement values between 9 and 11%. Figure 7c depicts the percentage improvement of IWCA and IWCA+FBS algorithms relative to standard WCA optimizer. The IWCA improved the standard WCA in terms of min., avg., and max. Results for 11 test cases in the range of 2–8%, while the corresponding improvement for IWCA+FBS algorithm is approximately 20–24%. Figure 7d shows the network performance improvement of standard HS and HS + FBS algorithms for the same network of traffic junctions [117]. The improvement for HS + FBS algorithm compared to standard HS optimizer are between 2 and 12% for min., avg., and max. Results for the considered cases.
Figure 7.
(a) Results comparison with different sampling times for network of 100 junctions, (b) the % improvement of iJaya and iJaya+FBS with standard Jaya, (c) the % improvement IWCA and IWCA+FBS with standard Jaya, (d) the % improvement HS + FBS and standard HS. Ref. [117].
Figure 8 presents the graphical comparison among the three optimization algorithms (iJaya+FBS, IWCA+FBS, and HS + FBS) in terms of the average relative percentage deviation (ARPD) of the resulting network delay time values [117]. It is clear from the results that the IWCA+FBS algorithm with an average delay reduction of 28.54% outperformed the iJaya+FBS and HS + FBS having the corresponding values of 28.22% and 27.84%, respectively. Further, all the algorithms yielded an improvement of at least 26% in the worst-case scenarios.
Figure 8.
ARPD improvements comparison for different optimizers. Reprinted with permission from Ref. [117] copyright (2021), Elsevier Ltd.
6.3 Water cycle algorithm (WCA)
The water cycle algorithm (WCA) is another recently proposed metaheuristic whose search mechanism is inspired by the natural water cycle process, where streams and rivers flow down the hill to reach the sea [130]. The surface run-off model is imitated in WCA for updating the current candidate solutions and the generation of new offspring. The effectiveness of WCA has been explored for various applications such as truss structures, constrained and unconstrained engineering design problems [130, 131, 132, 133]. However, very few studies have used WCO for traffic control, management, and optimization.
A recent study by Gao et al. proposed the application WCO for traffic signal scheduling and optimization based on actual traffic data from a case study in Singapore [121]. WCO was compared with four other metaheuristics and a hybrid algorithm (ABC-LS), considering the network delay as the main optimization objective. Numerical simulation results proved the benefits of adopting metaheuristic-based traffic control strategies instead of existing fixed traffic light schemes. In another study, Gao et al. compared WCO with the Jaya algorithm and Harmony search using the field traffic data from the same transportation network. The performance metric minimized the network-wide total traffic delay within a given time horizon [117]. The study proposed a neighborhood search operator to enhance the search performance of all the algorithms in the local search space. Study results showed that WCA, with an average better improvement of in network-wide delay (28.54%), outperformed HS (28.22%) and Jaya algorithm (27.84%).
7. Conclusions, current challenges, and future research directions
Traffic control and management using metaheuristics have emerged as an effective solution to mitigate urban congestion. This study provided a comprehensive review of state-of-art research on traffic signal optimization using different metaheuristics approaches. The surveyed literature is categorized based on the nature of applied metaheuristics, i.e., swarm intelligence (SI) techniques, evolutionary algorithms, trajectory-based metaheuristics, and others. Although numerous metaheuristics have been employed for signal optimization, GA, PSO, ACO, and ABC algorithms have been widely explored. Various traffic signal parameters such as cycle length, green splits, offsets, and phasing sequence are considered decision variables to solve signal control optimization problems. Similarly, studies have considered several optimization objectives such as delay, number of stops, travel time, throughput, queue, fuel consumption, exhaust emissions to address the problem. Some studies have adopted single-objective optimization, while others have attempted to solve traffic signal control as a multi-objective optimization problem. However, little work has been done to understand the correlations between the conflicting objectives which is vital for traffic engineers and decision-makers to evaluate their relative importance. Based on the presented survey work, the following passages present key challenges, research gaps, and future research directions in this area.
The review has shown that most of the previous works have adopted a single metaheuristic method for TSC optimization. However, very few studies have investigated the applicability of hybrid or ensemble metaheuristics for solving TSC optimization problems. In general, hybrid techniques are more useful than traditional metaheuristics. Hence, the application of hybrid metaheuristics for signal optimization could be a promising research direction.
Traditional evolutionary algorithms and swarm intelligence optimizers could yield acceptable solutions. However, the performance of these optimization techniques may be compared with recent state-of-the-art optimization approaches such as Teaching Learning Based Optimization Algorithm (TLBOA), Gravitational Search Algorithms (GSA), Rock Hyraxes Swarm Optimization (RHSO), hyper-heuristics, which are not explored yet for traffic signal optimization problems.
The literature review also noted that most previous studies were focused on single-objective optimization; however, traffic engineers often have to deal with multiple conflicting objectives to optimize the performance at the network level. Alternatively, for multiobjective optimization, the vast majority of existing works introduce weights for different objectives and consequently tackle signal optimization as a signal objective optimization problem. To optimize different performance indicators along optimal paretofront, multiple objectives have to be properly optimized. Developing an optimizer for multi-objective scenarios remains a challenging issue and is worth exploring in future studies.
Objective functions based on energy consumption and exhaust emissions have become a topic of increasing interest in recent years. From the reviewed literature, it was concluded that various approximate fuel consumptions and emission models were used for signal control optimization. Application of such approximate models could lead to an un-realistic traffic light setting. Future studies should consider the calibration of fuel consumption and emission models for a given network.
It was also evident from the presented literature that there is a shortage of research on statistical performance evaluation of proposed metaheuristics. Therefore, it would be interesting to explore the statistical analysis of such optimization strategies in terms of worst, average, and best results. Likewise, statistical significance tests may be conducted to compare the performance among various metaheuristics in solving signal optimization problems.
Lack of appropriate validation protocol is another important issue. Some studies have employed mere traffic simulation platforms to assess the validity of applied metaheuristics, while others have used them for isolated intersection scenarios or small traffic networks. Network optimization has become popular in recent years. For achieving desired improvements at the network level, the methods should be tested for large-scale complex transportation networks.
The surveyed literature also indicated that most previous studies considered only vehicular traffic and neglected the pedestrian traffic in solving the TSC problem using metaheuristics. It is important to consider all forms of traffic and driving systems to improve the overall efficiency of the transport system.
The surveyed literature also revealed that many studies develop metaheuristic-based traffic control considering specific traffic demand conditions, neglecting the other potential scenarios. It is essential to consider all ranges of traffic flow conditions (undersaturated, saturated, and oversaturated flow conditions) and traffic disturbances in developing metaheuristic to address TSC optimization problems.
The accuracy and reliability of the signal timing plan obtained using metaheuristics are highly dependent on the accuracy of traffic flow prediction models. In recent years, with rapid advances in computational power, big data technology has been successfully used for accurate traffic flow prediction. Therefore, the application of metaheuristics coupled with big data technology for traffic signal optimization appears to be another interesting research direction.
Acknowledgments
The authors acknowledge the support of the King Fahd University of Petroleum and Minerals, KFUPM, Dhahran Saudi Arabia, and Qassim University, Burudah, Saudi Arabia, for Supporting this study.
Conflict of interest
“The authors declare no conflict of interest.”
\n',keywords:"metaheuristics, intelligent traffic control, signal optimization, swarm intelligence, evolutionary computation, transport networks",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/78022.pdf",chapterXML:"https://mts.intechopen.com/source/xml/78022.xml",downloadPdfUrl:"/chapter/pdf-download/78022",previewPdfUrl:"/chapter/pdf-preview/78022",totalDownloads:180,totalViews:0,totalCrossrefCites:1,dateSubmitted:"November 16th 2020",dateReviewed:"July 15th 2021",datePrePublished:"September 7th 2021",datePublished:null,dateFinished:"August 11th 2021",readingETA:"0",abstract:"Intelligent traffic control at signalized intersections in urban areas is vital for mitigating congestion and ensuring sustainable traffic operations. Poor traffic management at road intersections may lead to numerous issues such as increased fuel consumption, high emissions, low travel speeds, excessive delays, and vehicular stops. The methods employed for traffic signal control play a crucial role in evaluating the quality of traffic operations. Existing literature is abundant, with studies focusing on applying regression and probability-based methods for traffic light control. However, these methods have several shortcomings and can not be relied on for heterogeneous traffic conditions in complex urban networks. With rapid advances in communication and information technologies in recent years, various metaheuristics-based techniques have emerged on the horizon of signal control optimization for real-time intelligent traffic management. This study critically reviews the latest advancements in swarm intelligence and evolutionary techniques applied to traffic control and optimization in urban networks. The surveyed literature is classified according to the nature of the metaheuristic used, considered optimization objectives, and signal control parameters. The pros and cons of each method are also highlighted. 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Harkut"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_1_2",title:"1.1 Traffic congestion: a challenging front",level:"2"},{id:"sec_2_2",title:"1.2 Traffic signal control (TSC)",level:"2"},{id:"sec_3_2",title:"1.3 Classical methods for TSC",level:"2"},{id:"sec_4_2",title:"1.4 Limitations of classical TSC strategies",level:"2"},{id:"sec_5_2",title:"1.5 Metaheuristics for TSC: the new frontier",level:"2"},{id:"sec_6_2",title:"1.6 Study objectives",level:"2"},{id:"sec_7_2",title:"1.7 Paper organization",level:"2"},{id:"sec_9",title:"2. Methodology",level:"1"},{id:"sec_10",title:"3. Review of evolutionary algorithms (EAs) for TSC",level:"1"},{id:"sec_10_2",title:"3.1 Genetic algorithm",level:"2"},{id:"sec_11_2",title:"3.2 Differential evolution (DE)",level:"2"},{id:"sec_12_2",title:"3.3 Genetic programming (GP)",level:"2"},{id:"sec_14",title:"4. Review of swarm intelligence (SI) techniques for TSC",level:"1"},{id:"sec_14_2",title:"4.1 Particle swarm optimization (PSO)",level:"2"},{id:"sec_15_2",title:"4.2 Ant colony optimization (ACO)",level:"2"},{id:"sec_16_2",title:"4.3 Artificial bee colony (ABC)",level:"2"},{id:"sec_17_2",title:"4.4 Cuckoo search (CS)",level:"2"},{id:"sec_18_2",title:"4.5 Bat algorithm (BA)",level:"2"},{id:"sec_19_2",title:"4.6 Artificial immune system (AIS)/immune network algorithm (INA)",level:"2"},{id:"sec_20_2",title:"4.7 Firefly algorithm (FA)",level:"2"},{id:"sec_21_2",title:"4.8 Gray wolf optimizer (GWO)",level:"2"},{id:"sec_23",title:"5. Review of trajectory-based metaheuristics for TSC",level:"1"},{id:"sec_23_2",title:"5.1 Tabu search for signal control optimization",level:"2"},{id:"sec_24_2",title:"5.2 Simulated annealing (SA)",level:"2"},{id:"sec_26",title:"6. 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Zhang et al., “Application of an enhanced BP neural network model with water cycle algorithm on landslide prediction,” Stochastic Environmental Research and Risk Assessment, pp. 1-19, 2020.'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Arshad Jamal",address:"arshad.jamal@kfupm.edu.sa",affiliation:'
Department of Civil and Environmental Engineering, King Fahd University of Petroleum and Minerals, Saudi Arabia
'},{corresp:null,contributorFullName:"Hassan M. Al-Ahmadi",address:null,affiliation:'
Department of Civil and Environmental Engineering, King Fahd University of Petroleum and Minerals, Saudi Arabia
'},{corresp:null,contributorFullName:"Farhan Muhammad Butt",address:null,affiliation:'
Department of Transportation and Traffic Engineering, College of Engineering, Imam Abdulrahman Bin Faisal University, Saudi Arabia
Shanghai Key Laboratory for Digital Maintenance of Buildings and Infrastructure, School of Naval Architecture, Ocean and Civil Engineering, Shangai Jiao Tong University, China
Department of Civil Engineering, University of Engineering and Technology Peshawar, Pakistan
Mechanical and Energy Engineering Department, Imam Abdulrahman Bin Faisal University, KSA
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Hunter",authors:[{id:"176855",title:"Dr.",name:"Wayne",middleName:null,surname:"Hunter",slug:"wayne-hunter",fullName:"Wayne Hunter"},{id:"177693",title:"Dr.",name:"Eduardo",middleName:null,surname:"Andrade",slug:"eduardo-andrade",fullName:"Eduardo Andrade"}]},{id:"43162",doi:"10.5772/52704",title:"Non-Viral Delivery Systems in Gene Therapy",slug:"non-viral-delivery-systems-in-gene-therapy",totalDownloads:4223,totalCrossrefCites:13,totalDimensionsCites:33,abstract:null,book:{id:"3509",slug:"gene-therapy-tools-and-potential-applications",title:"Gene Therapy",fullTitle:"Gene Therapy - Tools and Potential Applications"},signatures:"Alicia Rodríguez Gascón, Ana del Pozo-Rodríguez and María Ángeles Solinís",authors:[{id:"156696",title:"Dr.",name:"Alicia",middleName:null,surname:"Rodríguez Gascón",slug:"alicia-rodriguez-gascon",fullName:"Alicia Rodríguez Gascón"}]},{id:"30029",doi:"10.5772/34438",title:"The Legume Root Nodule: From Symbiotic Nitrogen Fixation to Senescence",slug:"the-legume-root-nodule-from-symbiotic-nitrogen-fixation-to-senescence",totalDownloads:4701,totalCrossrefCites:18,totalDimensionsCites:32,abstract:null,book:{id:"1446",slug:"senescence",title:"Senescence",fullTitle:"Senescence"},signatures:"Laurence Dupont, Geneviève Alloing, Olivier Pierre, Sarra El Msehli, Julie Hopkins, Didier Hérouart and Pierre Frendo",authors:[{id:"100143",title:"Dr.",name:"Pierre",middleName:null,surname:"Frendo",slug:"pierre-frendo",fullName:"Pierre Frendo"},{id:"100842",title:"Dr.",name:"Laurence",middleName:null,surname:"Dupont",slug:"laurence-dupont",fullName:"Laurence Dupont"},{id:"100848",title:"Dr.",name:"Geneviève",middleName:null,surname:"Alloing",slug:"genevieve-alloing",fullName:"Geneviève Alloing"},{id:"100852",title:"MSc.",name:"Sarra",middleName:null,surname:"El Msehli",slug:"sarra-el-msehli",fullName:"Sarra El Msehli"},{id:"100854",title:"MSc.",name:"Olivier",middleName:null,surname:"Pierre",slug:"olivier-pierre",fullName:"Olivier Pierre"},{id:"100859",title:"BSc.",name:"Julie",middleName:null,surname:"Hopkins",slug:"julie-hopkins",fullName:"Julie Hopkins"},{id:"100860",title:"Prof.",name:"Didier",middleName:null,surname:"Hérouart",slug:"didier-herouart",fullName:"Didier Hérouart"}]},{id:"49590",doi:"10.5772/61807",title:"Management of Insect Pest by RNAi — A New Tool for Crop Protection",slug:"management-of-insect-pest-by-rnai-a-new-tool-for-crop-protection",totalDownloads:3737,totalCrossrefCites:17,totalDimensionsCites:28,abstract:"The fast-growing human population requires the development of new agricultural technologies to meet consumers´ demand, while minimizing environmental impacts. Insect pests are one of the main causes for losses in agriculture production, and current control technologies based on pesticide application or the use of transgenic crops expressing Bacillus thuringiensis toxin proteins are facing efficacy challenges. Novel approaches to control pests are urgently necessary. RNA interference (RNAi) is a gene silencing mechanism triggered by providing double-stranded RNA (dsRNA), that when ingested into insects can lead to death or affect the viability of the target pest. Transgenic plants expressing dsRNA version of insect specific target genes are the new generation of resistant plants. However, the RNAi mechanism is not conserved among insect orders, and its elucidation is the key to develop commercial RNAi crops. In this chapter, we review the core RNAi pathway in insects and the dsRNA uptake, amplification, and spread of systemic silencing signals in some key insect species. We also highlight some of the experimental steps before developing an insect-pest-resistant “RNAi plant”. Lastly, we review some of the most recent development studies to control agricultural insect pests by RNAi transgenic plants.",book:{id:"5090",slug:"rna-interference",title:"RNA Interference",fullTitle:"RNA Interference"},signatures:"Thais Barros Rodrigues and Antonio Figueira",authors:[{id:"176770",title:"Dr.",name:"Thais B.",middleName:null,surname:"Rodrigues",slug:"thais-b.-rodrigues",fullName:"Thais B. Rodrigues"},{id:"176820",title:"Dr.",name:"Antonio",middleName:null,surname:"Figueira",slug:"antonio-figueira",fullName:"Antonio Figueira"}]}],mostDownloadedChaptersLast30Days:[{id:"50471",title:"Molecular Mechanisms of Skin Aging and Rejuvenation",slug:"molecular-mechanisms-of-skin-aging-and-rejuvenation",totalDownloads:5117,totalCrossrefCites:6,totalDimensionsCites:13,abstract:"The aging process in the skin is complex and influenced by more intrinsic and extrinsic factors than any other body organ. The effects of these two types of factors overlap for the most part. The combined effects of these two aging processes also affect dermal matrix alterations. The main clinical signs of skin aging include wrinkling and irregular pigmentation, which are influenced by a combination of intrinsic and extrinsic (e.g., UV radiation, heat, smoking, and pollutants) factors. Histologically, collagen decreases, and the dermis is replaced by abnormal elastic fibers as a cause of wrinkle formation through the loss of skin elasticity. There have been numerous studies of skin aging performed to elucidate the underlying molecular mechanisms and to develop various antiaging therapeutics and preventive strategies. We summarized the molecular mechanisms and treatments of skin aging. Mainly UV radiation induces ROS formation and DNA damage, leading to increased production of MMPs and decreased production of collagen in keratinocytes and fibroblasts, which reflect the central aspects of skin aging. Besides UV radiation exposure, extrinsic factors including tobacco smoking, exposure to environmental pollutants, infrared radiation, and heat contribute to premature skin aging. Like UV radiation, these factors cause ROS formation and increase expression of MMPs, thus accelerating skin aging by inducing extracellular matrix (ECM) degradation. Accumulated collagen fibrils inhibit the new collagen synthesis and account for the further degradation of the ECM through this positive feedback loop. Accumulating evidence for molecular mechanisms of skin aging should provide clinicians with an expanding spectrum of therapeutic targets in the treatment of skin aging.",book:{id:"5258",slug:"molecular-mechanisms-of-the-aging-process-and-rejuvenation",title:"Molecular Mechanisms of the Aging Process and Rejuvenation",fullTitle:"Molecular Mechanisms of the Aging Process and Rejuvenation"},signatures:"Miri Kim and Hyun Jeong Park",authors:[{id:"47695",title:"Prof.",name:"Hyun Jeong",middleName:null,surname:"Park",slug:"hyun-jeong-park",fullName:"Hyun Jeong Park"},{id:"185767",title:"Prof.",name:"Miri",middleName:null,surname:"Kim",slug:"miri-kim",fullName:"Miri Kim"}]},{id:"49637",title:"RNA Interference Technology — Applications and Limitations",slug:"rna-interference-technology-applications-and-limitations",totalDownloads:4079,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"RNA interference (RNAi), an evolutionarily conserved mechanism triggered by double-stranded RNA (dsRNA), causes gene silencing in a sequence-specific manner. RNAi evolved naturally to mediate protection from both endogenous and exogenous pathogenic nucleic acids and to modulate gene expression. Multiple technological advancements and precision in gene targeting have allowed a plethora of potential applications, ranging from targeting infections in crop plants to improving health in human patients, which have been reviewed in this chapter.",book:{id:"5090",slug:"rna-interference",title:"RNA Interference",fullTitle:"RNA Interference"},signatures:"Devi Singh, Sarika Chaudhary, Rajendra Kumar, Preeti Sirohi,\nKamiya Mehla, Anil Sirohi, Shashi Kumar, Pooran Chand and Pankaj\nKumar Singh",authors:[{id:"176625",title:"Prof.",name:"Devi",middleName:null,surname:"Singh",slug:"devi-singh",fullName:"Devi Singh"},{id:"176744",title:"Ms.",name:"Preeti",middleName:null,surname:"Sirohi",slug:"preeti-sirohi",fullName:"Preeti Sirohi"},{id:"176745",title:"Dr.",name:"Rajendra",middleName:null,surname:"Kumar",slug:"rajendra-kumar",fullName:"Rajendra Kumar"},{id:"176746",title:"Mrs.",name:"Sarika",middleName:null,surname:"Chaudhary",slug:"sarika-chaudhary",fullName:"Sarika Chaudhary"},{id:"176747",title:"Dr.",name:"Kamiya",middleName:null,surname:"Mehla",slug:"kamiya-mehla",fullName:"Kamiya Mehla"},{id:"176748",title:"Dr.",name:"Pankaj Kumar",middleName:null,surname:"Singh",slug:"pankaj-kumar-singh",fullName:"Pankaj Kumar Singh"},{id:"176749",title:"Dr.",name:"Shashi",middleName:null,surname:"Kumar",slug:"shashi-kumar",fullName:"Shashi Kumar"},{id:"176809",title:"Dr.",name:"Pooran",middleName:null,surname:"Chand",slug:"pooran-chand",fullName:"Pooran Chand"}]},{id:"43280",title:"Gene Therapy for Diabetic Retinopathy – Targeting the Renin-Angiotensin System",slug:"gene-therapy-for-diabetic-retinopathy-targeting-the-renin-angiotensin-system",totalDownloads:2443,totalCrossrefCites:2,totalDimensionsCites:2,abstract:null,book:{id:"3509",slug:"gene-therapy-tools-and-potential-applications",title:"Gene Therapy",fullTitle:"Gene Therapy - Tools and Potential Applications"},signatures:"Qiuhong Li, Amrisha Verma, Ping Zhu, Bo Lei, Yiguo Qiu, Takahiko Nakagawa, Mohan K Raizada and William W Hauswirth",authors:[{id:"155578",title:"Dr.",name:"Qiuhong",middleName:null,surname:"Li",slug:"qiuhong-li",fullName:"Qiuhong Li"}]},{id:"49416",title:"Microinjection-Based RNA Interference Method in the Water Flea, Daphnia pulex and Daphnia magna",slug:"microinjection-based-rna-interference-method-in-the-water-flea-daphnia-pulex-and-daphnia-magna",totalDownloads:2176,totalCrossrefCites:4,totalDimensionsCites:7,abstract:"It is well known that most daphnid species have several attractive life history characteristics such as cyclical parthenogenesis, environmental sex determination, and predator-induced defense formation. Recent advances in high-throughput omics technologies make it easy to obtain a huge number of potential candidate factors involved in environmental stimuli-triggered phenotypic alterations. Furthermore, our group has developed a microinjection system to introduce foreign materials such as nucleotides and chemicals into the early-stage (one-cell stage) egg of Daphnia pulex and Daphnia magna. Consequently, we established a microinjection-based RNAi system that allows arbitrary gene functions to be investigated. However, this microinjection system does not seem to have pervaded in the daphnid research community due to its low throughput and high level of skills required. In this chapter, we review the microinjection method and its RNAi system in water fleas, D. pulex and D. magna, providing some technical tips and making challenging proposals for the development of novel high-throughput RNAi methods. Finally, we provide an overview of recently developed gene functional analysis methods such as overexpression and genome-editing systems.",book:{id:"5090",slug:"rna-interference",title:"RNA Interference",fullTitle:"RNA Interference"},signatures:"Kenji Toyota, Shinichi Miyagawa, Yukiko Ogino and Taisen Iguchi",authors:[{id:"92826",title:"Dr.",name:"Taisen",middleName:null,surname:"Iguchi",slug:"taisen-iguchi",fullName:"Taisen Iguchi"},{id:"176835",title:"Dr.",name:"Kenji",middleName:null,surname:"Toyota",slug:"kenji-toyota",fullName:"Kenji Toyota"}]},{id:"55603",title:"RNA‐seq: Applications and Best Practices",slug:"rna-seq-applications-and-best-practices",totalDownloads:3710,totalCrossrefCites:7,totalDimensionsCites:8,abstract:"RNA‐sequencing (RNA‐seq) is the state‐of‐the‐art technique for transcriptome analysis that takes advantage of high‐throughput next‐generation sequencing. Although being a powerful approach, RNA‐seq imposes major challenges throughout its steps with numerous caveats. There are currently many experimental options available, and a complete comprehension of each step is critical to make right decisions and avoid getting into inconclusive results. A complete workflow consists of: (1) experimental design; (2) sample and library preparation; (3) sequencing; and (4) data analysis. RNA‐seq enables a wide range of applications such as the discovery of novel genes, gene/transcript quantification, and differential expression and functional analysis. This chapter will encompass the main aspects from sample preparation to downstream data analysis. It will be discussed how to obtain high‐quality samples, replicates amount, library preparation, sequencing platforms and coverage, focusing on best recommended practices based on specialized literature. Basic techniques and well‐known algorithms are presented and discussed, guiding both beginners and experienced users in the implementation of reliable experiments.",book:{id:"5944",slug:"applications-of-rna-seq-and-omics-strategies-from-microorganisms-to-human-health",title:"Applications of RNA-Seq and Omics Strategies",fullTitle:"Applications of RNA-Seq and Omics Strategies - From Microorganisms to Human Health"},signatures:"Michele Araújo Pereira, Eddie Luidy Imada and Rafael Lucas Muniz\nGuedes",authors:[{id:"202103",title:"Ph.D. Student",name:"Michele",middleName:"Araújo",surname:"Pereira",slug:"michele-pereira",fullName:"Michele Pereira"},{id:"202456",title:"MSc.",name:"Eddie Luidy",middleName:null,surname:"Imada",slug:"eddie-luidy-imada",fullName:"Eddie Luidy Imada"},{id:"202460",title:"Dr.",name:"Rafael",middleName:null,surname:"Guedes",slug:"rafael-guedes",fullName:"Rafael Guedes"}]}],onlineFirstChaptersFilter:{topicId:"419",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:288,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"25",title:"Environmental Sciences",doi:"10.5772/intechopen.100362",issn:"2754-6713",scope:"
\r\n\tScientists have long researched to understand the environment and man’s place in it. The search for this knowledge grows in importance as rapid increases in population and economic development intensify humans’ stresses on ecosystems. Fortunately, rapid increases in multiple scientific areas are advancing our understanding of environmental sciences. Breakthroughs in computing, molecular biology, ecology, and sustainability science are enhancing our ability to utilize environmental sciences to address real-world problems. \r\n\tThe four topics of this book series - Pollution; Environmental Resilience and Management; Ecosystems and Biodiversity; and Water Science - will address important areas of advancement in the environmental sciences. They will represent an excellent initial grouping of published works on these critical topics.
",coverUrl:"https://cdn.intechopen.com/series/covers/25.jpg",latestPublicationDate:"April 13th, 2022",hasOnlineFirst:!1,numberOfPublishedBooks:1,editor:{id:"197485",title:"Dr.",name:"J. Kevin",middleName:null,surname:"Summers",slug:"j.-kevin-summers",fullName:"J. Kevin Summers",profilePictureURL:"https://mts.intechopen.com/storage/users/197485/images/system/197485.jpg",biography:"J. Kevin Summers is a Senior Research Ecologist at the Environmental Protection Agency’s (EPA) Gulf Ecosystem Measurement and Modeling Division. He is currently working with colleagues in the Sustainable and Healthy Communities Program to develop an index of community resilience to natural hazards, an index of human well-being that can be linked to changes in the ecosystem, social and economic services, and a community sustainability tool for communities with populations under 40,000. He leads research efforts for indicator and indices development. Dr. Summers is a systems ecologist and began his career at the EPA in 1989 and has worked in various programs and capacities. This includes leading the National Coastal Assessment in collaboration with the Office of Water which culminated in the award-winning National Coastal Condition Report series (four volumes between 2001 and 2012), and which integrates water quality, sediment quality, habitat, and biological data to assess the ecosystem condition of the United States estuaries. He was acting National Program Director for Ecology for the EPA between 2004 and 2006. He has authored approximately 150 peer-reviewed journal articles, book chapters, and reports and has received many awards for technical accomplishments from the EPA and from outside of the agency. Dr. Summers holds a BA in Zoology and Psychology, an MA in Ecology, and Ph.D. in Systems Ecology/Biology.",institutionString:null,institution:{name:"Environmental Protection Agency",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"38",title:"Pollution",coverUrl:"https://cdn.intechopen.com/series_topics/covers/38.jpg",isOpenForSubmission:!0,editor:{id:"110740",title:"Dr.",name:"Ismail M.M.",middleName:null,surname:"Rahman",slug:"ismail-m.m.-rahman",fullName:"Ismail M.M. Rahman",profilePictureURL:"https://mts.intechopen.com/storage/users/110740/images/2319_n.jpg",biography:"Ismail Md. Mofizur Rahman (Ismail M. M. Rahman) assumed his current responsibilities as an Associate Professor at the Institute of Environmental Radioactivity, Fukushima University, Japan, in Oct 2015. He also has an honorary appointment to serve as a Collaborative Professor at Kanazawa University, Japan, from Mar 2015 to the present. \nFormerly, Dr. Rahman was a faculty member of the University of Chittagong, Bangladesh, affiliated with the Department of Chemistry (Oct 2002 to Mar 2012) and the Department of Applied Chemistry and Chemical Engineering (Mar 2012 to Sep 2015). Dr. Rahman was also adjunctly attached with Kanazawa University, Japan (Visiting Research Professor, Dec 2014 to Mar 2015; JSPS Postdoctoral Research Fellow, Apr 2012 to Mar 2014), and Tokyo Institute of Technology, Japan (TokyoTech-UNESCO Research Fellow, Oct 2004–Sep 2005). \nHe received his Ph.D. degree in Environmental Analytical Chemistry from Kanazawa University, Japan (2011). He also achieved a Diploma in Environment from the Tokyo Institute of Technology, Japan (2005). Besides, he has an M.Sc. degree in Applied Chemistry and a B.Sc. degree in Chemistry, all from the University of Chittagong, Bangladesh. \nDr. Rahman’s research interest includes the study of the fate and behavior of environmental pollutants in the biosphere; design of low energy and low burden environmental improvement (remediation) technology; implementation of sustainable waste management practices for treatment, handling, reuse, and ultimate residual disposition of solid wastes; nature and type of interactions in organic liquid mixtures for process engineering design applications.",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"201020",title:"Dr.",name:"Zinnat Ara",middleName:null,surname:"Begum",slug:"zinnat-ara-begum",fullName:"Zinnat Ara Begum",profilePictureURL:"https://mts.intechopen.com/storage/users/201020/images/system/201020.jpeg",biography:"Zinnat A. Begum received her Ph.D. in Environmental Analytical Chemistry from Kanazawa University in 2012. She achieved her Master of Science (M.Sc.) degree with a major in Applied Chemistry and a Bachelor of Science (B.Sc.) in Chemistry, all from the University of Chittagong, Bangladesh. Her work affiliations include Fukushima University, Japan (Visiting Research Fellow, Institute of Environmental Radioactivity: Mar 2016 to present), Southern University Bangladesh (Assistant Professor, Department of Civil Engineering: Jan 2015 to present), and Kanazawa University, Japan (Postdoctoral Fellow, Institute of Science and Engineering: Oct 2012 to Mar 2014; Research fellow, Venture Business Laboratory, Advanced Science and Social Co-Creation Promotion Organization: Apr 2018 to Mar 2021). The research focus of Dr. Zinnat includes the effect of the relative stability of metal-chelator complexes in the environmental remediation process designs and the development of eco-friendly soil washing techniques using biodegradable chelators.",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorThree:null},{id:"39",title:"Environmental Resilience and Management",coverUrl:"https://cdn.intechopen.com/series_topics/covers/39.jpg",isOpenForSubmission:!0,editor:{id:"137040",title:"Prof.",name:"Jose",middleName:null,surname:"Navarro-Pedreño",slug:"jose-navarro-pedreno",fullName:"Jose Navarro-Pedreño",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRAXrQAO/Profile_Picture_2022-03-09T15:50:19.jpg",biography:"Full professor at University Miguel Hernández of Elche, Spain, previously working at the University of Alicante, Autonomous University of Madrid and Polytechnic University of Valencia. Graduate in Sciences (Chemist), graduate in Geography and History (Geography), master in Water Management, Treatment, master in Fertilizers and Environment and master in Environmental Management; Ph.D. in Environmental Sciences. His research is focused on soil-water and waste-environment relations, mainly on soil-water and soil-waste interactions under different management and waste reuse. His work is reflected in more than 230 communications presented in national and international conferences and congresses, 29 invited lectures from universities, associations and government agencies. 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He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNVJQA4/Profile_Picture_2022-03-07T13:23:04.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Associate Prof.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/15648_n.jpg",biography:"Dr. Mohd Aftab Siddiqui is currently working as Assistant Professor in the Faculty of Pharmacy, Integral University, Lucknow for the last 6 years. He has completed his Doctor in Philosophy (Pharmacology) in 2020 from Integral University, Lucknow. He completed his Bachelor in Pharmacy in 2013 and Master in Pharmacy (Pharmacology) in 2015 from Integral University, Lucknow. He is the gold medalist in Bachelor and Master degree. He qualified GPAT -2013, GPAT -2014, and GPAT 2015. His area of research is Pharmacological screening of herbal drugs/ natural products in liver and cardiac diseases. He has guided many M. Pharm. research projects. He has many national and international publications.",institutionString:"Integral University",institution:null},{id:"255360",title:"Dr.",name:"Usama",middleName:null,surname:"Ahmad",slug:"usama-ahmad",fullName:"Usama Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255360/images/system/255360.png",biography:"Dr. Usama Ahmad holds a specialization in Pharmaceutics from Amity University, Lucknow, India. He received his Ph.D. degree from Integral University. Currently, he’s working as an Assistant Professor of Pharmaceutics in the Faculty of Pharmacy, Integral University. From 2013 to 2014 he worked on a research project funded by SERB-DST, Government of India. He has a rich publication record with more than 32 original articles published in reputed journals, 3 edited books, 5 book chapters, and a number of scientific articles published in ‘Ingredients South Asia Magazine’ and ‘QualPharma Magazine’. He is a member of the American Association for Cancer Research, International Association for the Study of Lung Cancer, and the British Society for Nanomedicine. Dr. Ahmad’s research focus is on the development of nanoformulations to facilitate the delivery of drugs that aim to provide practical solutions to current healthcare problems.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"30568",title:"Prof.",name:"Madhu",middleName:null,surname:"Khullar",slug:"madhu-khullar",fullName:"Madhu Khullar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/30568/images/system/30568.jpg",biography:"Dr. Madhu Khullar is a Professor of Experimental Medicine and Biotechnology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She completed her Post Doctorate in hypertension research at the Henry Ford Hospital, Detroit, USA in 1985. She is an editor and reviewer of several international journals, and a fellow and member of several cardiovascular research societies. Dr. Khullar has a keen research interest in genetics of hypertension, and is currently studying pharmacogenetics of hypertension.",institutionString:"Post Graduate Institute of Medical Education and Research",institution:{name:"Post Graduate Institute of Medical Education and Research",country:{name:"India"}}},{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",biography:"Xianquan Zhan received his MD and Ph.D. in Preventive Medicine at West China University of Medical Sciences. He received his post-doctoral training in oncology and cancer proteomics at the Central South University, China, and the University of Tennessee Health Science Center (UTHSC), USA. He worked at UTHSC and the Cleveland Clinic in 2001–2012 and achieved the rank of associate professor at UTHSC. Currently, he is a full professor at Central South University and Shandong First Medical University, and an advisor to MS/PhD students and postdoctoral fellows. He is also a fellow of the Royal Society of Medicine and European Association for Predictive Preventive Personalized Medicine (EPMA), a national representative of EPMA, and a member of the American Society of Clinical Oncology (ASCO) and the American Association for the Advancement of Sciences (AAAS). He is also the editor in chief of International Journal of Chronic Diseases & Therapy, an associate editor of EPMA Journal, Frontiers in Endocrinology, and BMC Medical Genomics, and a guest editor of Mass Spectrometry Reviews, Frontiers in Endocrinology, EPMA Journal, and Oxidative Medicine and Cellular Longevity. He has published more than 148 articles, 28 book chapters, 6 books, and 2 US patents in the field of clinical proteomics and biomarkers.",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",country:{name:"China"}}},{id:"297507",title:"Dr.",name:"Charles",middleName:"Elias",surname:"Assmann",slug:"charles-assmann",fullName:"Charles Assmann",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/297507/images/system/297507.jpg",biography:"Charles Elias Assmann is a biologist from Federal University of Santa Maria (UFSM, Brazil), who spent some time abroad at the Ludwig-Maximilians-Universität München (LMU, Germany). He has Masters Degree in Biochemistry (UFSM), and is currently a PhD student at Biochemistry at the Department of Biochemistry and Molecular Biology of the UFSM. His areas of expertise include: Biochemistry, Molecular Biology, Enzymology, Genetics and Toxicology. He is currently working on the following subjects: Aluminium toxicity, Neuroinflammation, Oxidative stress and Purinergic system. Since 2011 he has presented more than 80 abstracts in scientific proceedings of national and international meetings. Since 2014, he has published more than 20 peer reviewed papers (including 4 reviews, 3 in Portuguese) and 2 book chapters. He has also been a reviewer of international journals and ad hoc reviewer of scientific committees from Brazilian Universities.",institutionString:"Universidade Federal de Santa Maria",institution:{name:"Universidade Federal de Santa Maria",country:{name:"Brazil"}}},{id:"217850",title:"Dr.",name:"Margarete Dulce",middleName:null,surname:"Bagatini",slug:"margarete-dulce-bagatini",fullName:"Margarete Dulce Bagatini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217850/images/system/217850.jpeg",biography:"Dr. Margarete Dulce Bagatini is an associate professor at the Federal University of Fronteira Sul/Brazil. She has a degree in Pharmacy and a PhD in Biological Sciences: Toxicological Biochemistry. She is a member of the UFFS Research Advisory Committee\nand a member of the Biovitta Research Institute. She is currently:\nthe leader of the research group: Biological and Clinical Studies\nin Human Pathologies, professor of postgraduate program in\nBiochemistry at UFSC and postgraduate program in Science and Food Technology at\nUFFS. She has experience in the area of pharmacy and clinical analysis, acting mainly\non the following topics: oxidative stress, the purinergic system and human pathologies, being a reviewer of several international journals and books.",institutionString:"Universidade Federal da Fronteira Sul",institution:{name:"Universidade Federal da Fronteira Sul",country:{name:"Brazil"}}},{id:"226275",title:"Ph.D.",name:"Metin",middleName:null,surname:"Budak",slug:"metin-budak",fullName:"Metin Budak",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226275/images/system/226275.jfif",biography:"Metin Budak, MSc, PhD is an Assistant Professor at Trakya University, Faculty of Medicine. He has been Head of the Molecular Research Lab at Prof. Mirko Tos Ear and Hearing Research Center since 2018. His specializations are biophysics, epigenetics, genetics, and methylation mechanisms. He has published around 25 peer-reviewed papers, 2 book chapters, and 28 abstracts. He is a member of the Clinical Research Ethics Committee and Quantification and Consideration Committee of Medicine Faculty. His research area is the role of methylation during gene transcription, chromatin packages DNA within the cell and DNA repair, replication, recombination, and gene transcription. His research focuses on how the cell overcomes chromatin structure and methylation to allow access to the underlying DNA and enable normal cellular function.",institutionString:"Trakya University",institution:{name:"Trakya University",country:{name:"Turkey"}}},{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",slug:"anca-pantea-stoian",fullName:"Anca Pantea Stoian",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",biography:"Anca Pantea Stoian is a specialist in diabetes, nutrition, and metabolic diseases as well as health food hygiene. She also has competency in general ultrasonography.\n\nShe is an associate professor in the Diabetes, Nutrition and Metabolic Diseases Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. She has been chief of the Hygiene Department, Faculty of Dentistry, at the same university since 2019. Her interests include micro and macrovascular complications in diabetes and new therapies. Her research activities focus on nutritional intervention in chronic pathology, as well as cardio-renal-metabolic risk assessment, and diabetes in cancer. She is currently engaged in developing new therapies and technological tools for screening, prevention, and patient education in diabetes. \n\nShe is a member of the European Association for the Study of Diabetes, Cardiometabolic Academy, CEDA, Romanian Society of Diabetes, Nutrition and Metabolic Diseases, Romanian Diabetes Federation, and Association for Renal Metabolic and Nutrition studies. She has authored or co-authored 160 papers in national and international peer-reviewed journals.",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",country:{name:"Romania"}}},{id:"279792",title:"Dr.",name:"João",middleName:null,surname:"Cotas",slug:"joao-cotas",fullName:"João Cotas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/279792/images/system/279792.jpg",biography:"Graduate and master in Biology from the University of Coimbra.\n\nI am a research fellow at the Macroalgae Laboratory Unit, in the MARE-UC – Marine and Environmental Sciences Centre of the University of Coimbra. My principal function is the collection, extraction and purification of macroalgae compounds, chemical and bioactive characterization of the compounds and algae extracts and development of new methodologies in marine biotechnology area. \nI am associated in two projects: one consists on discovery of natural compounds for oncobiology. The other project is the about the natural compounds/products for agricultural area.\n\nPublications:\nCotas, J.; Figueirinha, A.; Pereira, L.; Batista, T. 2018. An analysis of the effects of salinity on Fucus ceranoides (Ochrophyta, Phaeophyceae), in the Mondego River (Portugal). Journal of Oceanology and Limnology. in press. DOI: 10.1007/s00343-019-8111-3",institutionString:"Faculty of Sciences and Technology of University of Coimbra",institution:null},{id:"279788",title:"Dr.",name:"Leonel",middleName:null,surname:"Pereira",slug:"leonel-pereira",fullName:"Leonel Pereira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/279788/images/system/279788.jpg",biography:"Leonel Pereira has an undergraduate degree in Biology, a Ph.D. in Biology (specialty in Cell Biology), and a Habilitation degree in Biosciences (specialization in Biotechnology) from the Faculty of Science and Technology, University of Coimbra, Portugal, where he is currently a professor. In addition to teaching at this university, he is an integrated researcher at the Marine and Environmental Sciences Center (MARE), Portugal. His interests include marine biodiversity (algae), marine biotechnology (algae bioactive compounds), and marine ecology (environmental assessment). Since 2008, he has been the author and editor of the electronic publication MACOI – Portuguese Seaweeds Website (www.seaweeds.uc.pt). He is also a member of the editorial boards of several scientific journals. Dr. Pereira has edited or authored more than 20 books, 100 journal articles, and 45 book chapters. He has given more than 100 lectures and oral communications at various national and international scientific events. He is the coordinator of several national and international research projects. In 1998, he received the Francisco de Holanda Award (Honorable Mention) and, more recently, the Mar Rei D. Carlos award (18th edition). He is also a winner of the 2016 CHOICE Award for an outstanding academic title for his book Edible Seaweeds of the World. In 2020, Dr. Pereira received an Honorable Mention for the Impact of International Publications from the Web of Science",institutionString:"University of Coimbra",institution:{name:"University of Coimbra",country:{name:"Portugal"}}},{id:"61946",title:"Dr.",name:"Carol",middleName:null,surname:"Bernstein",slug:"carol-bernstein",fullName:"Carol Bernstein",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/61946/images/system/61946.jpg",biography:"Carol Bernstein received her PhD in Genetics from the University of California (Davis). She was a faculty member at the University of Arizona College of Medicine for 43 years, retiring in 2011. Her research interests focus on DNA damage and its underlying role in sex, aging and in the early steps of initiation and progression to cancer. In her research, she had used organisms including bacteriophage T4, Neurospora crassa, Schizosaccharomyces pombe and mice, as well as human cells and tissues. She authored or co-authored more than 140 scientific publications, including articles in major peer reviewed journals, book chapters, invited reviews and one book.",institutionString:"University of Arizona",institution:{name:"University of Arizona",country:{name:"United States of America"}}},{id:"182258",title:"Dr.",name:"Ademar",middleName:"Pereira",surname:"Serra",slug:"ademar-serra",fullName:"Ademar Serra",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/182258/images/system/182258.jpeg",biography:"Dr. Serra studied Agronomy on Universidade Federal de Mato Grosso do Sul (UFMS) (2005). He received master degree in Agronomy, Crop Science (Soil fertility and plant nutrition) (2007) by Universidade Federal da Grande Dourados (UFGD), and PhD in agronomy (Soil fertility and plant nutrition) (2011) from Universidade Federal da Grande Dourados / Escola Superior de Agricultura Luiz de Queiroz (UFGD/ESALQ-USP). Dr. Serra is currently working at Brazilian Agricultural Research Corporation (EMBRAPA). His research focus is on mineral nutrition of plants, crop science and soil science. Dr. Serra\\'s current projects are soil organic matter, soil phosphorus fractions, compositional nutrient diagnosis (CND) and isometric log ratio (ilr) transformation in compositional data analysis.",institutionString:"Brazilian Agricultural Research Corporation",institution:{name:"Brazilian Agricultural Research Corporation",country:{name:"Brazil"}}}]}},subseries:{item:{id:"92",type:"subseries",title:"Health and Wellbeing",keywords:"Ecology, Ecological, Nature, Health, Wellbeing, Health production",scope:"
\r\n\tSustainable approaches to health and wellbeing in our COVID 19 recovery needs to focus on ecological approaches that prioritize our relationships with each other, and include engagement with nature, the arts and our heritage. This will ensure that we discover ways to live in our world that allows us and other beings to flourish. We can no longer rely on medicalized approaches to health that wait for people to become ill before attempting to treat them. We need to live in harmony with nature and rediscover the beauty and balance in our everyday lives and surroundings, which contribute to our well-being and that of all other creatures on the planet. This topic will provide insights and knowledge into how to achieve this change in health care that is based on ecologically sustainable practices.
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