Sequential organ failure assessment (SOFA) score [2].
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"3788",leadTitle:null,fullTitle:"Convergence and Hybrid Information Technologies",title:"Convergence and Hybrid Information Technologies",subtitle:null,reviewType:"peer-reviewed",abstract:"Starting a journey on the new path of converging information technologies is the aim of the present book. Extended on 27 chapters, the book provides the reader with some leading-edge research results regarding algorithms and information models, software frameworks, multimedia, information security, communication networks, and applications. Information technologies are only at the dawn of a massive transformation and adaptation to the complex demands of the new upcoming information society. It is not possible to achieve a thorough view of the field in one book. Nonetheless, the editor hopes that the book can at least offer the first step into the convergence domain of information technologies, and the reader will find it instructive and stimulating.",isbn:null,printIsbn:"978-953-307-068-1",pdfIsbn:"978-953-51-5915-5",doi:"10.5772/235",price:139,priceEur:155,priceUsd:179,slug:"convergence-and-hybrid-information-technologies",numberOfPages:438,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"41060ee16becdd7639b6821bb50963ce",bookSignature:"Marius Crisan",publishedDate:"March 1st 2010",coverURL:"https://cdn.intechopen.com/books/images_new/3788.jpg",numberOfDownloads:80688,numberOfWosCitations:72,numberOfCrossrefCitations:72,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:115,numberOfDimensionsCitationsByBook:3,hasAltmetrics:0,numberOfTotalCitations:259,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"July 30th 2013",dateEndSecondStepPublish:"August 20th 2013",dateEndThirdStepPublish:"November 24th 2013",dateEndFourthStepPublish:"February 22nd 2014",dateEndFifthStepPublish:"March 24th 2014",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"4577",title:"Professor",name:"Marius",middleName:null,surname:"Crisan",slug:"marius-crisan",fullName:"Marius Crisan",profilePictureURL:"https://mts.intechopen.com/storage/users/4577/images/system/4577.jpg",biography:"Marius Crisan was born in Timisoara, Romania in 1955. 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He is member of IEEE and ACM.\n\nHis primary research interests include natural language processing and modeling, cognitive science, information theory, and artificial intelligence. 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\r\n\tThe optic nerve is one of the largest nerve bundles in the human central nervous system and its structure and functioning have been extensively studied in the past years. Modern diagnosis techniques are now available and, for instance, we can leverage advanced imaging techniques which help us provide insights into a range of disorders such as neuritis associated with multiple sclerosis, neuromyelitis optica spectrum disorder, glaucoma, and Leber's hereditary optic neuropathy, ischemic optic neuropathy. Other optic nerve disorders are caused by external toxic agents such as drugs, metals, organic solvents, and methanol. Nutritional deficiencies (especially those related to an insufficient intake of B vitamins, folic acid, and proteins) are also crucial factors in reducing optic nerve functionality.
\r\n\r\n\t
\r\n\tThis book will aim to survey the most recent diagnostic techniques as well as the most promising therapeutic options we can count on to deal with optic nerve disorders. The audience of the book is quite wide and it aims at being the main entry to this fascinating topic for students, clinicians, and researchers.
The term sepsis derives from ancient Greek “sêpsis” (“putrefaction” or “decay of organic matter”) and was first used in a medical context in Homer’s Iliad more than 2700 years ago. Currently, sepsis is defined as a life-threatening organ dysfunction due to a dysregulated host response to infection [1]. Since 2016, the updated operative definition of sepsis no longer considers the presence of systemic inflammatory response syndrome, but requires an infection plus organ dysfunction indicated by an acute change in Sequential Organ Failure Assessment (SOFA) [2] of at least two points (see Table 1). Septic shock is defined as sepsis plus circulatory failure with increased risk of death, indicated by hypotension requiring vasopressor therapy to maintain a mean arterial pressure (MAP) 65 mmHg or greater and a serum lactate of greater than 2 mmol/L despite adequate fluid resuscitation [3]. Other indices of tissue hypoperfusion (e.g. altered mental status, oliguria, delayed capillary refill) are acceptable alternatives whenever serum lactate determination is not available.
System | Score | ||||
---|---|---|---|---|---|
0 | 1 | 2 | 3 | 4 | |
Respiration PaO2/FIO2, mmHg (kPa) | ≥400 (53.3) | <400 (53.3) | <300 (40) | <200 (26.7) with respiratory support | <100 (13.3) with respiratory support |
Coagulation platelets, ×103 μL−1 | ≥150 | <150 | <100 | <50 | <20 |
Liver bilirubin, mg dL−1 (μmol L−1) | <1.2 (20) | 1.2–1.9 (20–32) | 2.0–5.9 (33–101) | 6.0–11.9 (102–204) | >120 (204) |
Cardiovascular | MAP ≥70 mmHg | MAP<70 mmHg | Dopamine<5 or dobutamine (any dose)a | Dopamine 5.1–15 or epinephrine ≤0.1 or norepinephrine ≤0.1a | Dopamine >15 or epinephrine >0.1 or norepinephrine >0.1a |
Central nervous system (CNS) | |||||
Glasgow Coma Scale scoreb | 15 | 13–14 | 10–12 | 6–9 | <6 |
Renal creatinine, mg dL−1 (μmol L−1) < 1.2 (110) 1.2–1.9 (110–170) | 2.0–3.4 (171–299) | 3.5–4.9 (300–440) | >5.0 (440) | ||
Urine output, mL per day | <500 | <200 |
Sequential organ failure assessment (SOFA) score [2].
Catecholamine doses are given as μgkg−1 min−1 for at least 1 h.
Glasgow Coma Scale scores range from 3 to 15; higher score indicates belter neurological function.
FIO2, fraction of inspired oxygen; MAP, mean arterial pressure; PaO2, partial pressure of oxygen.
In high-income countries, sepsis represents approximately 6% of adult hospitalizations and 10–37% of intensive care unit (ICU) admissions. Mortality estimates from sepsis and septic shock vary widely, rounding 15% and 22% respectively [4]. In low-income regions, sepsis and septic shock predictably carry an even higher mortality, up to 50% [5].
Generally speaking, atrial fibrillation (AF) is the most frequently found cardiac arrhythmia in the ICU setting. Previously known AF is significantly prevalent among older patients with chronic conditions who are at risk for critical illness. New-onset AF (NOAF), on the other hand, is frequently triggered by accelerated atrial remodeling and by concomitant stressors during critical illness, such as electrolyte imbalances and use of vasopressor drugs [6].
In this narrative review, the pathogenesis, risk factors, incidence, prognosis and management of AF in septic shock patients are summarized.
The negative effects of sepsis on the heart are not limited to the contractile function and ventricular relaxation, but also affect the electric function. Although the precise mechanisms remain to be elucidated, inflammation seems to play an important role. The electrical instability of cardiomyocytes in patients with sepsis has been considered to be due to the use of vasopressor drugs and the presence of electrolyte disturbances. However, according to recent findings, atrial fibrillation (AF) could be the result of the necrosis and fibrosis induced by inflammation [7, 8]. These alterations are supposed to be able to trigger an arrhythmia due to a fluctuation in the myocardial cells’ membrane potential [9].
The development of NOAF in septic shock patients depends upon the presence of an arrhythmogenic substrate, the trigger factors and the modulation factors such as autonomic nervous system or inflammation. Triggered activity has been shown in the musculature of the atrium. An imbalance between sympathetic and vagal tone leading to a reduction of heart rate variability has been proposed as an explanation for the development of NOAF in septic patients [10]. Vagal stimulation normally attenuates the inflammatory response [11]. In human atrial cardiomyocytes, partial blockage of the I(f) ‘funny’ pacemaker current has been observed after exposition to gram-negative bacteria endotoxin [12], which may contribute to a reduced responsiveness to both sympathetic and vagal autonomic stimuli (the name “funny current” arose because of its numerous unusual characteristics, including the mixed Na + and K+ current permeability, activation on hyperpolarization, and slow activation and deactivation kinetics [13]) (see Figure 1). This would result in a high heart rate output, which is commonly observed in septic patients. Unopposed sustained tachycardia during the will further increase calcium influx through L-type Ca2+ channels, which leads to marked shortening of the atrial refractory period and action potential duration (Figure 1) and elicit triggered activity, hence facilitating the onset of AF [14, 15] (see Figure 2). This process has been shown to be further enhanced due to beta-adrenergic stimulation after endotoxin application [16], which increases channel activity by prolonging the open time and shortening the close time of Ca2+ channel. These findings might explain the high sensitivity of cardiac pacemaker cells to positive inotropic effect of adrenergic stimulation and most likely development of new AF episode especially in the early stages of sepsis [17].
Schematized transmembrane action potential of sinus node (pacemaker) cells. The black line shows normal slope in sinus rhythm. During gram-negative bacteria induced-sepsis, it has been shown I(f) current blockage, which results in an increased phase 4 slope, triggering sinus tachycardia and facilitating AF onset (red line) [
Schematized transmembrane action potential of atrial myocytes in normal and septic animals. The orange line indicates how sepsis decrease phase 2 (plateau phase) duration and leads to decrease in APD (action potential duration). This is due to a decrease in influx of calcium through the voltage-dependent L-channels, which is at least in part caused by sepsis-induced tachycardia. The decrease in APD (and hence in the atrial refractory period) has been proposed to effectively trigger AF [
Sepsis itself is a strong risk factor for NOAF in the critical care setting. An extensive retrospective population-based cohort analysis by Walkey et al. revealed that compared to those without severe sepsis, patients with severe sepsis (n = 49,082) exhibited a significantly increased risk of NOAF (odds ratio (OR), 6.82; 95% confidence interval (CI), 6.54–7.11; P < 0.001) [18]. Multiple studies have been shown that the classic risk factors for the development of chronic atrial fibrillation in the general population may differ from those present in septic patients with NOAF. Risk factors for the occurrence of NOAF in septic patients include conditions that are not related to chronic cardiovascular disease, such as increased number of acute organ failures/dysfunction, mechanical ventilation, increased comorbidities, and use of pulmonary artery catheterization [18, 19, 20, 21, 22]. NOAF has been also associated with lower EF, older age, higher level of troponin-HS and NT-pro-BNP and longer QRS duration.
Sepsis due to bacterial pneumonia has been associated with a high risk of developing NOAF, while sepsis due to gastrointestinal infections has been related to AF recurrence with worse long-term prognosis [23]. It has been hypothesized that the type and severity of infection could have an impact on the atrial remodeling and the variety of cytokine expression during sepsis. Current evidence suggests that the severity of the inflammatory response in critically ill patients is associated with a higher risk of NOAF, and septic shock patients have in general a heightened probability of developing NOAF than patients with other acute critical illnesses after adjustment for underlying risk factors [21].
In a systematic review that included 11 studies, Kuipers et al. [19] identified independent risk factors with a high level of evidence for NOAF in septic patients. White race, organ failure and pulmonary catheter use were moderately associated with NOAF development, while there was a weak association with age and respiratory tract infection. On the other hand, history of diabetes and urinary tract infections were found to be weak protective factors. In other studies, markers of illness severity (such as the presence of organ failure and shock) as well as several critical care interventions were associated with an increased risk of NOAF in septic patients. Known risk factors for chronic or paroxysmal AF in the general population, such as advanced age, white race, male gender, obesity and (ischemic) heart failure, were in some studies also associated with the development of AF during sepsis [24, 25]. Specific electrocardiographic or echocardiographic features of AF such as P-wave duration or left atrial area, remain to be studied in septic shock patients, although both factors are known to predict the occurrence of AF in the general population [26, 27].
Data regarding risk factors for the occurrence of NOAF in septic shock patients is more limited. Guenancia et al. [26] found that NOAF patients were older and had higher levels of cardiac biomarkers (troponin (p < 0.01) and NT-pro-BNP (p = 0.03)), lower left ventricular ejection fraction (LVEF), longer duration of the QRS complex and more nonsustained supraventricular arrhythmias (< 30 seconds) on day 1 than patients who maintained sinus rhythm. Age (OR: 1.06; p = 0.01) and LVEF <45% (OR: 13.01, p = 0.03) were associated with NOAF in their multivariate analysis.
Atrial fibrillation is a common occurrence in patients with sepsis and septic shock, and its incidence varies widely among investigators. This may be due to the different criteria used to define sepsis and septic shock, or the method used for the diagnosis of AF [28]. In the aforementioned systematic review, Kuipers et al. [19] showed that the mean incidence of new-onset AF was 8% in patients with sepsis and 23% in patients with septic shock. The authors of that study also observed a significant increase in ICU length of stay in this group of patients. In a large study conducted by Walkey et al. [21], which retrospectively analyzed data from over 60,000 patients admitted for sepsis, the investigators found an overall incidence of AF during sepsis of 25.5%. This number rose to 31.6% when considering only the ICU population.
To date, there have been relatively few published prospective investigations regarding the incidence of AF in septic shock patients, although there is more available information about the general topic of AF in septic patients. Seguin et al. [29] found AF developed in 24 patients (5.3%) of 460 patients admitted to the surgical intensive care unit and followed prospectively during a 6-month period. They reported that 29.2% (7 of 23 patients) of septic shock patients developed AF. They concluded the presence of shock (especially septic shock) appeared to be an independent risk factor of AF in their cohort. It has to be recognized, however, that the operative definition of septic shock used at that time, the one proposed by Bone et al. [30], has since been substantially modified.
Steinberg et al. [28] published recently a one-year observational prospective study of 27 septic shock patients. Their aim was to evaluate the incidence of AF, and the mortality rate of patients with AF versus patients that maintained sinus rhythm. Nine (33%) patients developed AF during the first 72 hours. At admission and at 72 hours, SOFA was statistically higher in the patients with AF (p = 0.012 and p = 0.002, respectively).
In a single-center study, Meierhenrich et al. [31] prospectively studied all patients with NOAF and all patients suffering from septic shock in ICU during a 13 month period. Patients with preexisting chronic AF were excluded from their analysis. They found 23 out of the 50 patients with septic shock (46%) developed NOAF, compared to an overall incidence (septic and non-septic patients taken into account) of NOAF of 7.8% (49/629). The same aforementioned limitation in septic shock definition applies to this data.
Guenancia et al. [26] conducted a single-center prospective, observational study on patients with septic shock, and they found an incidence of new-onset AF of 44% (29 of 66 patients). Noteworthy, a 34% of new-onset AF would not be diagnosed without Holter ECG monitoring (silent AF).
More recently—and using an updated definition of septic shock—Rabie et al. [32] prospectively studied 100 septic shock patients, one of the largest series ever published. All patients were continuously monitored by three/five-lead monitor with arrhythmia detection algorithms, alarms, and Holter recording capabilities throughout the ICU stay. The investigators found the development of NOAF in 29 (29%), of which 22 (75,8%) patients had a single occurrence and 7 (24,2%) had recurrent AF during their ICU stay.
Whether NOAF acts as a surrogate marker for increased illness severity and subsequently poor prognosis in sepsis or whether it directly contributes to mortality and poor outcomes is not entirely clear. As stated before, the sepsis state can trigger AF mainly because of the combined mechanisms of inflammation, surge in catecholamines, and direct and indirect myocardial injury, and the poor prognosis noted whenever AF develop in critically ill patients may be the consequence of the presence of these factors.
In a retrospective analysis, Walkey et al. [33] found that patients with NOAF during a hospitalization for sepsis showed a higher five-year risk of hospitalization for heart failure (11.2% vs. 8.2%; HR, 1.25; 95% CI, 1.16–1.34), ischemic stroke (5.3% vs. 4.7%; HR, 1.22; 95% CI, 1.15–1.47), and death (74.8% vs. 72.1%; HR, 1.04; 95% CI, 1.01–1.07) than patients who did not develop NOAF.
Specific prospective data regarding the prognosis of NOAF in septic shock patients is also sparse. In a small series of 27 septic shock patients followed prospectively for one year, Steinberg et al. [28] reported that mortality was higher in AF patients (66%) than in patients in sinus ryhtm (11%) (p = 0.006). Age, rhythm and noradrenaline dosage were univariate predictors of total mortality. In the aforementioned study of Meierhenrich et al. [31], mortality in septic shock patients with NOAF was 44% compared with 22% in septic shock patients with maintained sinus rhythm (p = 0.14). The average length of ICU stay was shown to be increased in patients with NOAF (30 versus 17 days, p = 0.017). Failure to achieve sinus rhythm restoration was associated with greater ICU mortality (71.4% vs. 21.4%, p = 0.015). After two years, the investigators observed a statistically nonsignificant increase in mortality in septic shock patients with NOAF (p = 0.075).
In a larger prospective series, Rabie et al. [32] found that mortality in patients with single AF attacks were not statistically higher than non-AF patients (p = 0.143). However, recurrent attacks of AF had significantly higher mortality than non-AF or single AF attack (p < 0.05). Recurrent AF was associated with increased length of UCI stay (21.6 ± 7.2 vs. 12.9 ± 7.3 days, p = 0.004).
When considering use of antiarrhythmic drugs or applying cardioversion in septic patients with atrial fibrillation and hemodynamic instability, causative factors must in parallel be addressed and corrected when feasible [34]. Since diastolic dysfunction is highly prevalent in ICU patients and is also an independent predictor of mortality [35], both excessive or insufficient fluid resuscitation should be avoided. For example, the so-called Early Goal Directed Therapy has shown marginal benefit [36] while heightening the risk of fluid overload and the overuse of betaadrenergic stimulant drugs to achieve central venous saturation above 65%. The resulting high cardiac output constitutes an arrhythmogenic setting. Interestingly, ceasing beta-stimulation and administering low-dose betablockers with concomitant preload correction has led to a dramatic decrease in mortality [37]. While the use of vasopressors in septic shock is recommended in early septic shock, preload assessment and timely administration of vasopressin can assist in diminishing the requirement of catecholaminergic drugs and consequently lower the risk of arrhythmia. Suboptimal volume replacement, on the other hand, carries the risk of higher sympathetic tone and consequent down-to regulation of adrenergic receptors which in turns leads to requirement of greater doses of vasopressor drugs. Hence, both conditions, namely fluid overload and hypovolaemia, are triggering factors for developing arrhythmias.
Electrolyte disturbances, which are commonplace in ICU patients, should be likewise identified and promptly corrected. Hypokalemia and hyperkalemia triggers supraventricular and ventricular arrhythmias. If the potassium level does not respond to adequate supplementation, magnesium levels must be assessed and corrected, since severe hypomagnesemia prevents the potassium level being corrected. It has been shown that septic patients tend to have lower serum magnesium levels when compared to nonseptic patients [38, 39]. Hypophosphatemia is associated with decreased myocardial contractility and a higher incidence of arrhythmia [40], and the correction of phosphorus level has been shown to prevent it [41]. Hypocalcemia may also be associated with arrhythmias [42, 43], although the data in septic patients is scarce.
Right ventricular dysfunction may cause acute cor pulmonale and supraventricular arrhythmias [44]. Instituting aggressive modalities of mechanical ventilation in septic patients with acute distress respiratory syndrome as an attempt to recruit consolidated lungs may trigger an increase in right ventricular afterload, with the consequent development of NOAF. Gradual opening of the consolidated lungs in a prone position [45] guided by periodic chest ultrasound and echocardiographic assessment may prevent the onset of supraventricular arrhythmias.
Guidelines for management of AF [46] do not usually apply readily to critically ill patients, since NOAF in patients treated on an ICU differs from AF in patients in the community in terms of causes of rhythm disturbance [47], and appropriate management [48].
Synchronized direct current cardioversion (SDCC) should be employed for patients with hemodynamic instability related to the arrhythmia, even though the probability of remaining in sinus rhythm may be low. In critically ill patients, SDCC has been investigated in few studies. The reported efficacy is generally low, ranging from 26.9% and 35.1% [49, 50]. Mayr et al. reported successful electrical cardioversion at one hour after the attempt in 13/37 (35.1%) ICU patients with NOAF. After 24 hours, six of these 37 patients (13.5%) remained in sinus rhythm. An additional study evaluating the efficacy of SDCC reported sinus rhythm restoration for at least 24 hours in 7/26 (26.9%) patients. Of note, 18 of these patients had received amiodarone prior to or during electrical cardioversion [49].
In septic shock patients with NOAF, there is lack of data on effectiveness. In a small series [28], SDCC was attempted in five patients due to hemodynamic instability. In three patients, the procedure was not effective, whereas, in one patient, sinus rhythm was restored. However, AF recurred shortly afterwards; and in one case, a stable sinus rhythm was obtained. The effectiveness of electrical therapy may be improved by concomitant antiarrhythmic medication. When electrically cardioverting 24% of septic shock patients on amiodarone and 36% on propafenone, the overall rate of sinus rhythm maintenance was significant (74% and 89%, respectively) [51]. After an initially successful cardioversion, failure to remain in sinus rhythm may signal a poor prognosis.
Amiodarone is a Vaughan-Williams class III antiarrhythmic drug that is frequently used to treat atrial fibrillation, both in community and ICU settings. It is currently approved for cardioversion of atrial fibrillation (Class I, level of evidence A) [52]. It is a highly lipophilic compound with a long half life, and it is eliminated by hepatic metabolism and not by dialysis [53]. Being one of the few antiarrhythmic drugs that does not affect significantly the left ventricular ejection fraction (LVEF), its use is however limited by the occasional occurrence of systemic hypotension and because of its relatively highly toxic profile, including thyroid, lung and liver dysfunction among other detrimental effects (eg, corneal microdeposits, skin discoloration and neuropathies).
Amiodarone success in terms of rhythm control in sepsis patients varies widely, from 30% [54] to 95% [55], although rates of sustained sinus rhythm after cardioversion are substantially lower. Comparative observational studies in ICU septic patients have shown that amiodarone achieved lower rates of rhythm control than beta-blockers, magnesium and calcium channel blockers [51, 54, 56].
Specific data on amiodarone effectiveness in septic shock patients is scant. Balik et al. [51] showed in a recent study on septic shock and supraventricular arrhythmias (AF being the most frequent encountered) that amiodarone was the drug of choice in 76% of patients, likely due to the hemodynamic instability of patients in septic shock on vasoactive agents. Restoration to sinus rhythm was achieved in 74% patients while 23.7% of them required additional electrical cardioversion. The median total dose of amiodarone was 3.0 (1.8–4.6) g, given by infusion over 4 (2–6) days with a median of 1.4 (0.9–1.8) g during the first day. Due to its limited efficacy to cardiovert and to maintain sinus rhythm (74%), the patients with a persisting arrhythmia were often switched to propafenone. Interestingly, in this study, successfully cardioverted patients (with either amiodarone, propafenone or metoprolol) or those having chronic AF demonstrated not significantly lower ICU and 28-day, and 12-month mortalities compared to patients remaining in an acute onset arrhythmia.
In a retrospective review of adult medical or surgical ICU patients with septic shock and NOAF that received amiodarone (n = 239), Betthauser et al. [57] found that exposure to more than or equal to 2700 mg of amiodarone was positively correlated with longer ICU length of stay. The same investigators found that compared to non-septic shock patients, septic shock patients did not show significant difference in hemodynamic deterioration within 72 hours of intravenous amiodarone administration. Of 105 patients surviving hospital discharge, 29% continued receiving oral amiodarone at discharge.
Propafenone is a Vaughan-Williams class IC antiarrhythmic drug with some (but clinically limited) beta-blocking activity as a result of a structural similarity to beta-adrenoceptor antagonists [58]. Propafenone is currently approved and used frequently for cardioversion of atrial fibrillation (Class I, level of evidence A) [52]. However, since CAST (the Cardiac Arrhythmia Suppression Trial) [59] revealed that class IC antiarrhythmic drugs flecainide and encainide could increase the mortality risk when administered to patients with ventricular arrhythmias and coronary artery disease with significant left ventricular systolic dysfunction, current guidelines have restricted the recommendation of this class of drugs (including propafenone) to patients with NOAF who do not have structural heart disease [52].
The aforementioned study by Balik et al. [51], suggests that propafenone could be a drug of choice in septic shock patients with normal to moderately reduced LVEF. Propafenone was used in septic shock patients with NOAF as a primary antiarrhythmic in 17.5% of patients, but this figure rises to 33% if one takes into account the patients who were not able to cardiovert and maintain a sinus rhythm on amiodarone and then received propafenone. The observed cardioversion success rate was 86.1% at 24 h, although 35.5% needed additional SDCC to restore sinus rhythm. The success of cardioversion was significantly higher with propafenone than with amiodarone and almost the same as metoprolol (93%). The average propafenone dose was 670 (460–700) mg/day. Compared with amiodarone, propafenone use did not result in significantly lower ICU and 28-day mortalities, but was associated with a 12-month mortality benefit, although patients in propafenone group tended to have better LVFE at baseline and lower dose of vasopressor drugs (e.g., norepinephrine), likely reflecting more severe compromise of septic shock in the amiodarone group [34].
Current guidelines recommend beta-blockers as first-choice drugs to control heart rate in AF patients with LVEF >40% (class I, level of evidence B) [52].
Autonomic dysfunction in septic shock may be accompanied by extreme tachycardia and high cardiac output. Tachycardia increases cardiac workload and myocardial oxygen consumption. In addition, shortening of diastolic relaxation time and impairment of diastolic function further affect coronary perfusion, contributing to a lower ischemic threshold. Although norepinephrine is the current recommended mainstay of treatment for sepsis-related hypotension, excessive adrenergic stress has multiple adverse effects including direct myocardial damage (e.g., takotsubo or stress cardiomyopathy and tachyarrhythmias), insulin resistance, thrombogenicity, immunosuppression, and enhanced bacterial growth [60]. Taken together, these mechanisms contribute to worsening of septic myocardial dysfunction and increased mortality [61].
The use of beta-adrenergic blockers has been proposed to mitigate the persistent sympathetic stimulation in septic shock patients, and this mechanism may in part be responsible of the observed improvement in prognosis. The production of cytokines may also be reduced with the consequent improvement in the metabolic dysregulation by means of reducing protein catabolism and by inhibiting gluconeogenesis [62]. On the other hand, using beta-blockers in septic shock patients is not without risks. Many patients with septic shock are already being treated with vasopressor and inotropic drugs, and treating them with beta-blockers can exacerbate hypotension and bradycardia promoting further hemodynamic instability [63].
In order to reduce the unnecessary load of catecholamines and the stimulation of their receptors, an easily titratable beta-blocker (e.g. esmolol or landiolol), may be safe in those patients who require vasopressor drugs in parallel for low systemic vascular resistance and hypotension. In an open-label, randomized single-center study (n = 154) by Morelli et al. [64], septic shock patients were assigned to receive a continuous infusion of esmolol titrated to maintain heart rate between 80/min and 94/min versus standard treatment. It was not specified how many of those patients had atrial fibrillation, so its main interest in this discussion relates to its tolerability, since traditionally it has been feared that betablockage in septic patients could result in hemodynamic deterioration. Nonetheless, the mean arterial pressure was maintained despite a marked reduction in norepinephrine requirements in the esmolol group. Also, stroke volume, systemic vascular resistance, and left ventricular stroke work indices were increased in the esmolol group. Noteworthy, it was shown that 28-day mortality was 49.4% in the esmolol group vs. 80.5% in the control group (adjusted hazard ratio, 0.39; 95% CI, 0.26 to 0.59; p < 0.001). These findings suggest that lowering of heart rate by esmolol allows better ventricular filling during diastole, hence improving stroke volume and thereby improving the efficiency of myocardial work and oxygen consumption.
Metoprolol is also well tolerated in septic shock patients with supraventricular arrhythmias. In septic shock patients with NOAF treated with intravenous metoprolol, Balik et al. [51] found that sinus rhythm was achieved in 92.3% patients with no additional electrical cardioversion. The median length of treatment was 5 (2–9) days, while the median intravenous metoprolol dose was 84 (48–120) mg/day.
A relatively new beta-blocker with high selectivity for beta1 receptors and a half-life of only 4 minutes, landiolol, has also been shown to be well tolerated in the critically ill for its limited negative inotropic effect and limited impact on blood pressure, as different Japanese teams of investigators have reported [65, 66, 67]. The use of low doses (5–10 mcg/kg/min) of landiolol is usually sufficient for the cardioversion of AF compared to controls. In sinus tachycardia, landiolol may prevent the occurrence of arrhythmias using an even lower dose (3–5 mcg/kg/min). In a multicenter, open-label, randomized controlled trial at 54 hospitals in Japan, in which 76 patients with sepsis or septic shock received intravenous landiolol and 75 patients were assigned to the control group, Kakihana et al. [68] found that Landiolol resulted in significantly more patients with sepsis-related tachyarrhythmia (55% vs. 33%, p = 0.031) achieving a heart rate of 60–94 bpm at 24 h and significantly reduced the incidence of new-onset arrhythmia. The investigators report that landiolol was also well tolerated, but should be used under appropriate monitoring of blood pressure and heart rate owing to the risk of hypotension in patients with sepsis and septic shock.
Balik et al. [34], based on studies on tachycardic patients with septic shock requiring catecholamine administration suggest the benefit of slowing heart rate by approximately 20%, but also warn that lowering heart rate below 100 per minute by means of betablockage may result in a cardiac output inadequate to meet the systemic oxygen demands in septic shock. Appropriately powered, randomized, controlled multicenter trials are required to further clarify the role of beta-blockers in septic shock patients with NOAF.
Digoxin and other cardiac glycosides have been long used to treat patients with heart failure and cardiac arrhythmias, atrial fibrillation among the latter. However, in the last couple of decades, various clinical trials have resulted in limiting the role of digoxin in the management of atrial fibrillation [52]. Digoxin acts at a cellular level by inhibiting the sodium-potassium pump, increasing the calcium availability to the contractile apparatus. This results in an increase in cardiac contractility and slowing of cardiac conduction through the atrioventricular node [69].
There is paucity of data regarding the use of digoxin in septic shock patients with NOAF. In a retrospective cohort study of ICU patients (n = 38,159) by Quian et al. [70], the investigators found an incidence of NOAF rounding 9%. After adjusting for multiple variables, they found that in patients with NOAF the use of digoxin was associated with an increased risk of 90-day mortality (hazard ratio 1.23, 95% CI 1.10–1.39, p < 0.001), although the proportion of sepsis patients in this population was not specified.
While many clinical trials have shown that warfarin therapy reduces the risk of thromboembolic complications in patients with AF, it has not been unequivocally proved that oral anticoagulants provide similar benefits in critically ill septic patients with AF without carrying a significant bleeding risk. So, a common dilemma arises when deciding which septic patients with AF should receive anticoagulation therapy [71]. Walkey et al. [72] studied the practice patterns of anticoagulation in 38,582 septic patients with AF. They found that more than a third (35.3%) of the patients were anticoagulated with intravenous heparin or subcutaneous enoxaparin, while the rest of the patients did not receive anticoagulants. In those who did, significant bleeding was more frequently observed (8.6% vs. 7,2%, RR 1.21). Interestingly, there was no significant difference in the risk of ischemic stroke between anticoagulated and non-anticoagulated patients (1.4% vs. 1.3%, RR 0.94, CI 0.78–1.12). Furthermore, there was no difference in the risk of ischemic stroke between patients with preexistent AF and those with NOAF (RR, 1,12).
In a retrospective observational study to assess the incidence of stroke and anticoagulation-related complications (e.g., bleeding, heparin-induced thrombocytopenia) in AF patients with severe sepsis (n = 115), Darwish et al. [71] found no statistically significant difference in survival rates during their hospitalization (66.2% [53/80] in the non-anticoagulated group versus 74.3% (26/35) in the anticoagulated group, P = 0.392). There were no reports of strokes in either arm of the study, but this finding is at least in part explained by the small number of patients and the short period of time used for assessment. Up to date, prospective, comparative robust evidence for anticoagulation in septic shock patients is lacking.
Due to its anti-inflammatory properties, low-dose hydrocortisone has been frequently used to achieve shock reversal and better outcomes in patients with septic shock [73]. However, after extensive review of the available evidence, the Surviving Sepsis Campaign’s guidelines restricted the use hydrocortisone in shock septic patients only when fluid resuscitation and vasopressor drugs failed to restore hemodynamic stability [74]. In a recent multicenter, prospective nonrandomized observational study in 261 septic shock patients, Launey et al. [75], a atrial fibrillation developed in 33 (24%) and 24 (19%) of no-hydrocortisone patients and hydrocortisone patients, respectively. In the weighted sample, the proportion of patients who developed AF was 28.8% in the nohydrocortisone group and 16.8% in the hydrocortisone group (difference: 11.9%; 95% confidence interval: 23.4% to 0.5%; p = 0.04), noting that patients who received hydrocortisone were more severely ill than those who did not receive hydrocortisone. Investigators conclude that low-dose hydrocortisone was associated with a lower risk of developing AF during the acute phase, although serious risk of bias due to missing covariates in the propensity score matching has to be taken into account.
AF during septic shock has been insufficiently studied. This has led to relevant uncertainties regarding its etiology, pathophysiology and appropriate management. Risk factors for chronic AF and NOAF frequently differ, and the unique pathophysiology of NOAF remains to be fully elucidated. Despite of a high probability of successful cardioversion achieved by pharmacological or electrical means, these treatment modalities have shown modest efficacy in affecting the medium and long-term prognosis of septic shock patients with AF. The benefits of anticoagulation in shock septic patients with AF have not been firmly established, while the risk of bleeding is increased in septic patients. Evidence-based guidelines and even expert consensus documents on the subject of NOAF management are lacking. Properly designed multicenter, prospective randomized trials are needed to clarify these questions.
Uropathogenic
Adhesins are adhesive organelles, notably fimbriae, that promote bacterial colonization. Some adhesins also promote bacterial invasion of the host cell. Adhesins are thought to be the most important virulence-associated molecules which function in UPEC pathogenicity. The adhesins can also directly trigger host and bacterial cell signaling pathways. They can also facilitate the delivery of other bacterial products to the host tissues [17]. Prominent bacterial cell surface virulence factors, which play significant roles in UPEC pathogenicity include type 1 fimbriae [11]; Class I, Class II, and Class III of P-fimbriae [18, 19, 20]; Dr. family of adhesins for binding to the decay-accelerating factor (DAF) [21]; Curli fimbriae which functions as binding factor and biofilm producer [22]; and S-fimbriae [14, 23, 24]. Type 1 fimbriae have the most significant effects in UTIs as they enhance bacterial survival and growth, enhance inflammatory reaction at the mucosa, bacterial invasion, and control biofilm production [7]. P-fimbriae have the second most prominent role in UPEC-associated pathogenesis of human ascending UTIs and pyelonephritis. They promote UPEC adherence to the matrix of the mucosa and tissues and trigger cytokine production [25, 26, 27, 28, 29, 30].
UPEC secrete several virulence toxins which are responsible for the damage of the host cells and host inflammatory response. α-hemolysin (HlyA) is the most virulent toxin produced by UPEC. The effects of HlyA in UTIs are dependent on its dosage produced by UPEC. At high concentration, HlyA destroys the erythrocytes and allow UPEC to break through the mucosal barriers, damage immune system, and depletes iron stores of the host [31, 32, 33, 34]. At low concentration, HlyA induces cell death in the bladder using proinflammatorycaspase-1/caspase-4. This causes kidney damage and scarring; oscillations of Ca2+; ascension and colonization of ureters and kidney parenchyma in the renal tubule epithelia resulting in the disruption of normal flow of urine [35, 36, 37, 38]. The stimulation of
Urinary tract has limited iron. However, UPEC are able to produce small iron chelator molecules, known as siderophores, to scavenge ferric iron (Fe3+) in the host. The most prominent ones are yersiniabactin, salmochelin, and aerobactin [48, 49]. The yersiniabactin and its receptor, FyuA, are encoded in a PAI [50, 51]. It has also been reported that for efficient biofilm formation by UPEC, FyuA is required [52]. UPEC also secretes another important hydroxamate siderophore called aerobactin. This is produced from the condensation of two lysine and a citrate molecules. During UPEC invasion, the bacterium secretes salmochelin. Its outer membrane siderophore receptor (IroN) transports different catechol siderophores, including N-(2,3-dihydroxybenzoy)-L-serine and enterochelin also called enterobactin [53]. Enterobactin has less solubility and stability than aerobactin [54, 55, 56] but has higher iron affinity than aerobactin in aqueous [55, 57]. UPEC also uses enterobactin for Fe3+ scavenging in the urinary tract [9]. However, enterobactin can be inactivated by the host proteins such as serum albumin and siderocalin thereby preventing its uptake [58]. UPEC overcomes this instability by modifying the enterobactin to salmochelin by glucosylation through the enzymatic action of glucosyltransferase and prevents it from being recognized by the host proteins [9]. Also, UPEC has another iron acquisition system called haemin uptake system consisting of Ton-B dependent receptor (ChuA) and heavy metal associated (
UPEC-associated fitness and virulence. Adapted from the work by Servin [
Lipopolysaccharide (LPS) is a major part of the cell wall which has highly conserved lipid A-core and repeating O-antigen subunits which vary in different strains of
Capsule is made up of polysaccharides and it covers and protects UPEC from various harsh environmental conditions [66]. The capsule helps UPEC to resist phagocytosis and bactericidal effects of complements in the host. It also confers antimicrobial resistance and antiserum activity to UPEC [54, 61]. Capsules like K1 and K5 interfere with the proper response of the humoral immunity of the infected host [66]. The K1 polysaccharide plays a significant role in intracellular bacterial community (IBC) development and the pathogenesis of several UTI stages [54, 67].
Toll receptor (TIR)/interleukin1 (IL-1) receptor domain-containing protein (TcpC) is a novel class of virulence factors that destabilize TIR signaling for UPEC to survive during UTIs [68]. Interaction of TcpC with myeloid differentiation primary response 88 (MyD88) found in the host ends the downstream signaling pathways mediated by TLRs [69].
UPEC produces outer membrane protease T (OmpT) that catalyzes plasminogen activation to plasmin [70]. OmpT helps UPEC to persist in the urinary tract when protamine and other cation peptides cleave with antibiotic activity [71, 72]. UPEC also decreases cytokines production by blocking nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB) [68]. In Table 1, prominent UPEC virulence factors, their role and genetic markers are presented.
Virulence factor | Role | Genetic markers/gene name | References |
---|---|---|---|
Afimbrial adhesions | Binding factor | [23, 24, 54] | |
Cytotoxic necrotizing factor 1 | Toxin | [38, 39] | |
Curlifimbriae | Binding factor | [22] | |
Dr family of adhesions | Binding factor | [21] | |
Haemin | Iron uptake and biofilm formation | [59, 60, 61] | |
Type 1 fimbriae | Binding factor | [8] | |
Ferric yersiniabactin uptake receptor | Iron uptake and biofilm formation | [62] | |
α-hemolysin | Lyses red blood cells | [33] | |
Salmochelin | Siderophore receptor | [51] | |
Aerobactin | Iron chelation and uptake | [50] | |
Outer membrane protease T | Outer membrane protease production to degrade protamine peptides | [73, 74] | |
Uropathogen specific protein | Movement of UPEC from the urinary tract to the bloodstream | [42] | |
Class I, Class II, and Class III P-fimbriae | For binding to the uroepithelial cells | [18, 20, 21] | |
Serine-protease autotransporter toxin | Vacuolation and tissue damage | [73, 74] | |
S-fimbrial family | Binding factor | [8, 23, 24] |
Virulence factors of uropathogenic
Apart from possessing virulence factors, for the medical importance of
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On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. 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Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. 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Cretoiu, Dragos Cretoiu Anca Simionescu and Laurentiu M. Popescu",authors:[{id:"65176",title:"Dr.",name:"Dragos",middleName:null,surname:"Cretoiu",slug:"dragos-cretoiu",fullName:"Dragos Cretoiu"},{id:"71558",title:"Dr.",name:"Sanda",middleName:"Maria",surname:"Cretoiu",slug:"sanda-cretoiu",fullName:"Sanda Cretoiu"},{id:"71561",title:"Dr.",name:"Anca",middleName:null,surname:"Simionescu",slug:"anca-simionescu",fullName:"Anca Simionescu"},{id:"71562",title:"Prof.",name:"Laurentiu M.",middleName:null,surname:"Popescu",slug:"laurentiu-m.-popescu",fullName:"Laurentiu M. 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Pereira, Maria J. Martins, Isabel Azevedo and Rosário Monteiro",authors:[{id:"74789",title:"Prof.",name:"Rosário",middleName:null,surname:"Monteiro",slug:"rosario-monteiro",fullName:"Rosário Monteiro"},{id:"74796",title:"Dr.",name:"Cidália",middleName:null,surname:"Pereira",slug:"cidalia-pereira",fullName:"Cidália Pereira"},{id:"74800",title:"Prof.",name:"Isabel",middleName:null,surname:"Azevedo",slug:"isabel-azevedo",fullName:"Isabel Azevedo"},{id:"160587",title:"Prof.",name:"Maria João",middleName:null,surname:"Martins",slug:"maria-joao-martins",fullName:"Maria João Martins"}]},{id:"27067",title:"Telocytes in Human Fallopian Tube and Uterus Express Estrogen and Progesterone Receptors",slug:"telocytes-in-human-fallopian-tube-and-uterus-express-estrogen-and-progesterone-receptors",totalDownloads:2272,totalCrossrefCites:0,totalDimensionsCites:22,abstract:null,book:{id:"805",slug:"sex-steroids",title:"Sex Steroids",fullTitle:"Sex Steroids"},signatures:"Sanda M. Cretoiu, Dragos Cretoiu Anca Simionescu and Laurentiu M. Popescu",authors:[{id:"65176",title:"Dr.",name:"Dragos",middleName:null,surname:"Cretoiu",slug:"dragos-cretoiu",fullName:"Dragos Cretoiu"},{id:"71558",title:"Dr.",name:"Sanda",middleName:"Maria",surname:"Cretoiu",slug:"sanda-cretoiu",fullName:"Sanda Cretoiu"},{id:"71561",title:"Dr.",name:"Anca",middleName:null,surname:"Simionescu",slug:"anca-simionescu",fullName:"Anca Simionescu"},{id:"71562",title:"Prof.",name:"Laurentiu M.",middleName:null,surname:"Popescu",slug:"laurentiu-m.-popescu",fullName:"Laurentiu M. Popescu"}]},{id:"27793",title:"Sex Steroids in Insects and the Role of the Endosymbiont Wolbachia:A New Perspective",slug:"sex-steroids-in-insects-and-the-role-of-the-endosymbiont-wolbachia-a-new-perspective",totalDownloads:3646,totalCrossrefCites:5,totalDimensionsCites:12,abstract:null,book:{id:"804",slug:"sex-hormones",title:"Sex Hormones",fullTitle:"Sex Hormones"},signatures:"Ilaria Negri and Marco Pellecchia",authors:[{id:"68168",title:"Dr.",name:"Ilaria",middleName:null,surname:"Negri",slug:"ilaria-negri",fullName:"Ilaria Negri"},{id:"74147",title:"Dr",name:"Marco",middleName:null,surname:"Pellecchia",slug:"marco-pellecchia",fullName:"Marco Pellecchia"}]},{id:"60756",title:"The Biological Role of Androgen Receptor in Prostate Cancer Progression",slug:"the-biological-role-of-androgen-receptor-in-prostate-cancer-progression",totalDownloads:1876,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Prostate cancer is the most commonly diagnosed cancer in men all over the world. Localized cancers in the early stages can be well managed by surgical or radiation therapy. Metastatic prostate cancer is treated with androgen deprivation therapy because androgen signaling is essential to the prostate tumor growth and anti-apoptotic ability. However, resistance develops quickly in the clinical course and leads to castration-resistant prostate cancer (CRPC). Androgen receptor (AR) functions as a nuclear receptor to facilitate ligand-dependent transcriptional activation in the nucleus. AR interacts with several tissue-specific transcription factors such as forkhead box protein A1 (FOXA1) and regulates epigenetic status by recruiting epigenetic factors. In addition, AR transcriptional activity is modulated by interacting directly or indirectly with non-coding RNAs such as long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs). Notably, enhanced AR signaling in CRPC has been documented in several studies; however, which of these factors are important for the biological function it remains poorly understood. Here, I review our current knowledge of the mechanistic roles of AR involved in prostate cancer progression and discuss the importance of the prostate cancer-associated signals.",book:{id:"6762",slug:"advances-in-testosterone-action",title:"Advances in Testosterone Action",fullTitle:"Advances in Testosterone Action"},signatures:"Ken-ichi Takayama",authors:[{id:"239221",title:"Dr.",name:"Ken-Ichi",middleName:null,surname:"Takayama",slug:"ken-ichi-takayama",fullName:"Ken-Ichi Takayama"}]},{id:"75047",title:"Role of Sex Hormones in Human Body",slug:"role-of-sex-hormones-in-human-body",totalDownloads:566,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Gonadal Steroids hormones play an important role in the reproductive and non-reproductive systems. Estrogen has important rule in cardiovascular system as it has vasodilator effect and reduces or prevents platelet activation. In addition, it improves the profile of circulating lipoproteins. All of which may explain why women at premenopausal age are less likely to have heart disease than menopause women or men. E2 play a grate effect on the skeletal system as it is one of the strongest regulators of osteoblast and osteoclast function, and it is responsible for the reduction of adipose tissue and regulation of the body weight, and also has dermatological effect,hence it stimulates the proliferation of keratinocytes and prevents their apoptosis, in addition to the progesterone which increases collagen synthesis. Estrogen is necessary for the functioning and integrity of the tissues of the urinary system specially of the lower urinary tract. Sex steroid are crucial for nervous system, as progesterone is important for production of neurosteroid, and estrogen is currently used in Parkinson’s and Alzheimer’s disease because of its effects on mental health. The androgens also have a crucial biological effects on neural, muscle, bone, adipose tissue,prostate, cardiovascular, haemopoietic, and the reproductive systems. The gonadal steroid hormones play an important role in immune system and regulating the immune response against different viral or bacterial infections.",book:{id:"10313",slug:"reproductive-hormones",title:"Reproductive Hormones",fullTitle:"Reproductive Hormones"},signatures:"Nassrin Malik Aubead",authors:[{id:"329956",title:"Dr.",name:"Nassrin",middleName:null,surname:"Malik Aubead",slug:"nassrin-malik-aubead",fullName:"Nassrin Malik Aubead"}]}],onlineFirstChaptersFilter:{topicId:"1014",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:31,numberOfPublishedChapters:314,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:11,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,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:18,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:14,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. This Series is intended for researchers and students alike interested in this fascinating field and its many applications.",coverUrl:"https://cdn.intechopen.com/series/covers/14.jpg",latestPublicationDate:"June 11th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"218714",title:"Prof.",name:"Andries",middleName:null,surname:"Engelbrecht",slug:"andries-engelbrecht",fullName:"Andries Engelbrecht",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNR8QAO/Profile_Picture_1622640468300",biography:"Andries Engelbrecht received the Masters and PhD degrees in Computer Science from the University of Stellenbosch, South Africa, in 1994 and 1999 respectively. He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). In addition to a number of research articles, he has written two books, Computational Intelligence: An Introduction and Fundamentals of Computational Swarm Intelligence.",institutionString:null,institution:{name:"Stellenbosch University",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:6,paginationItems:[{id:"22",title:"Applied Intelligence",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",isOpenForSubmission:!0,annualVolume:11418,editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,annualVolume:11419,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,annualVolume:11420,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,annualVolume:11421,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. He is a Senior Member of the IEEE Computer, the IEEE Computational Intelligence, and the IEEE Systems, Man, and Cybernetics Societies, and the Association of Computing Machinery (ACM). Finally, his main research interests include data science, computational intelligence, and their applications.",institutionString:null,institution:{name:"University of Córdoba",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"26",title:"Machine Learning and Data Mining",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",isOpenForSubmission:!0,annualVolume:11422,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. His research interests include intelligent and embedded systems.",institutionString:"Universidad Autonoma de Queretaro",institution:{name:"Autonomous University of Queretaro",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null},{id:"27",title:"Multi-Agent Systems",coverUrl:"https://cdn.intechopen.com/series_topics/covers/27.jpg",isOpenForSubmission:!0,annualVolume:11423,editor:{id:"148497",title:"Dr.",name:"Mehmet",middleName:"Emin",surname:"Aydin",slug:"mehmet-aydin",fullName:"Mehmet Aydin",profilePictureURL:"https://mts.intechopen.com/storage/users/148497/images/system/148497.jpg",biography:"Dr. Mehmet Emin Aydin is a Senior Lecturer with the Department of Computer Science and Creative Technology, the University of the West of England, Bristol, UK. His research interests include swarm intelligence, parallel and distributed metaheuristics, machine learning, intelligent agents and multi-agent systems, resource planning, scheduling and optimization, combinatorial optimization. Dr. Aydin is currently a Fellow of Higher Education Academy, UK, a member of EPSRC College, a senior member of IEEE and a senior member of ACM. In addition to being a member of advisory committees of many international conferences, he is an Editorial Board Member of various peer-reviewed international journals. He has served as guest editor for a number of special issues of peer-reviewed international journals.",institutionString:null,institution:{name:"University of the West of England",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:19,paginationItems:[{id:"82196",title:"Multi-Features Assisted Age Invariant Face Recognition and Retrieval Using CNN with Scale Invariant Heat Kernel Signature",doi:"10.5772/intechopen.104944",signatures:"Kamarajugadda Kishore Kumar and Movva Pavani",slug:"multi-features-assisted-age-invariant-face-recognition-and-retrieval-using-cnn-with-scale-invariant-",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Pattern Recognition - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11442.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"82063",title:"Evaluating Similarities and Differences between Machine Learning and Traditional Statistical Modeling in Healthcare Analytics",doi:"10.5772/intechopen.105116",signatures:"Michele Bennett, Ewa J. Kleczyk, Karin Hayes and Rajesh Mehta",slug:"evaluating-similarities-and-differences-between-machine-learning-and-traditional-statistical-modelin",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Machine Learning and Data Mining - Annual Volume 2022",coverURL:"https://cdn.intechopen.com/books/images_new/11422.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"81791",title:"Self-Supervised Contrastive Representation Learning in Computer Vision",doi:"10.5772/intechopen.104785",signatures:"Yalin Bastanlar and Semih Orhan",slug:"self-supervised-contrastive-representation-learning-in-computer-vision",totalDownloads:23,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Pattern Recognition - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11442.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"79345",title:"Application of Jump Diffusion Models in Insurance Claim Estimation",doi:"10.5772/intechopen.99853",signatures:"Leonard Mushunje, Chiedza Elvina Mashiri, Edina Chandiwana and Maxwell Mashasha",slug:"application-of-jump-diffusion-models-in-insurance-claim-estimation-1",totalDownloads:8,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Data Clustering",coverURL:"https://cdn.intechopen.com/books/images_new/10820.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}}]},overviewPagePublishedBooks:{paginationCount:9,paginationItems:[{type:"book",id:"7723",title:"Artificial Intelligence",subtitle:"Applications in Medicine and Biology",coverURL:"https://cdn.intechopen.com/books/images_new/7723.jpg",slug:"artificial-intelligence-applications-in-medicine-and-biology",publishedDate:"July 31st 2019",editedByType:"Edited by",bookSignature:"Marco Antonio Aceves-Fernandez",hash:"a3852659e727f95c98c740ed98146011",volumeInSeries:1,fullTitle:"Artificial Intelligence - Applications in Medicine and Biology",editors:[{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. His research interests include intelligent and embedded systems.",institutionString:"Universidad Autonoma de Queretaro",institution:{name:"Autonomous University of Queretaro",institutionURL:null,country:{name:"Mexico"}}}]},{type:"book",id:"7726",title:"Swarm Intelligence",subtitle:"Recent Advances, New Perspectives and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/7726.jpg",slug:"swarm-intelligence-recent-advances-new-perspectives-and-applications",publishedDate:"December 4th 2019",editedByType:"Edited by",bookSignature:"Javier Del Ser, Esther Villar and Eneko Osaba",hash:"e7ea7e74ce7a7a8e5359629e07c68d31",volumeInSeries:2,fullTitle:"Swarm Intelligence - Recent Advances, New Perspectives and Applications",editors:[{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null}]},{type:"book",id:"7656",title:"Fuzzy Logic",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7656.jpg",slug:"fuzzy-logic",publishedDate:"February 5th 2020",editedByType:"Edited by",bookSignature:"Constantin Volosencu",hash:"54f092d4ffe0abf5e4172a80025019bc",volumeInSeries:3,fullTitle:"Fuzzy Logic",editors:[{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. 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