\r\n\t1. 90% of girls fully vaccinated with HPV vaccine by age 15 years. \r\n\t2. 70% of women are screened with a high-performance test by 35 years and again by 45 years \r\n\t3. 90% of women identified with cervical disease receive treatment (90% of women with precancer treated, and 90% of women with invasive cancer managed
\r\n
\r\n\tThis book “glows in teal”, committing itself, to the noble task of elimination of HPV infections and related cancers. This book has, well experienced and dedicated scientists from all over the world, contributing chapters in the fields of Epidemiology of HPV; HPV Vaccination – Efficacy – acceptance, affordability and policies; Pathophysiology and carcinogenesis of HPV; Hi-Tech screening protocols, methodologies for HPV testing; Diagnosis and treatment of Pre cancers and invasive cancers due to HPV; Prevention and control of Papillomaviridae infections and related Cancers of Cervix, Vagina, Vulva, Penis, Anus and Oropharynx.
\r\n
\r\n\tWe, firmly hope that the knowledge shared in this book would immensely contribute to the global goal of elimination of Papillomavidae and related cancers, and serve as a beacon of “teal light” symbolizing cancer eradication, from the lighthouse of Scientific wisdom and Social welfare, The InTech publishers."
",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:"b7612146e5bd35247afd8bb1b6913be8",bookSignature:"Dr. Rajamanickam Rajkumar",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11370.jpg",keywords:"Incidence, Prevalence, Determinants, Awareness, Transmission, Pathophysiology, Oncogenesis, Host Cell Changes, DNA Alterations, HPV Screening, HPV Vaccination, Types of Vaccines",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 3rd 2021",dateEndSecondStepPublish:"November 11th 2021",dateEndThirdStepPublish:"January 10th 2022",dateEndFourthStepPublish:"March 31st 2022",dateEndFifthStepPublish:"May 30th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"8 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:"Professor Dr. Rajamanickam Rajkumar, is a Champion for the cause of Cervical Cancer Elimination HPV Research, in rural India, from 2000, in collaboration with the IARC/WHO, The Ohio State University Medical Center -USA, and The Society for Colposcopy and Cervical Pathology Singapore.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"120109",title:"Dr.",name:"Rajamanickam",middleName:null,surname:"Rajkumar",slug:"rajamanickam-rajkumar",fullName:"Rajamanickam Rajkumar",profilePictureURL:"https://mts.intechopen.com/storage/users/120109/images/system/120109.png",biography:"Rajamanickam Rajkumar is an international frontline scientist in cervical cancer and HPV prevention with a Ph.D. in Cancer Epidemiology. 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1. Introduction
Even though liver disease remains the main cause of ascites, there are several other causes including renal diseases, infections (tuberculosis), malignancies, and heart disease (Table 1).
It is important to diagnose the etiology of ascites in order to properly treat it.
Detailed history, physical examination, laboratory blood test, abdominal ultrasound, and serum albumin ascitic gradient are important in narrowing the differential diagnosis of ascites.
Cirrhosis is the eighth leading cause of death in the United States [1]. Ascites is one of the most common complications of cirrhosis that leads to hospital admissions [2]. It occurs due to portal hypertension and is primarily related to an inability to excrete an adequate amount of sodium into urine, leading to positive sodium balance leading to fluid retention [3]. Many patients are referred for liver transplantation after development of ascites. Evidence suggests that arterial splanchnic vasodilation leads to renal sodium and water retention in patients with cirrhosis. This permits dropping in effective arterial blood capacity with stimulation of arterial as well as cardiopulmonary volume receptors, in addition to homeostatic stimulation of vasoconstrictor and sodium-retaining systems (i.e., the RAAS (renin-angiotensin-aldosterone system) as well as the sympathetic nervous system). Renal sodium preservation causes extension of the extracellular fluid volume and accumulation of ascites and edema [4, 5]. The occurrence of ascites is directly linked to worse prognosis and compromised life quality; therefore, patients should be turned over to liver transplant center for evaluation [6]. Nearly 75% of the patients with ascites in Western Europe or the United States have cirrhosis as the primary cause. The remaining 25% of the ascites is caused by malignancy, heart failure, tuberculosis, pancreatic disease, or other miscellaneous causes [7].
Determining the cause of ascites is very important for appropriate management. The serum-ascites albumin gradient (SAAG) can be helpful for both diagnostic and therapeutic purposes. Patients with a high SAAG (≥1.1 g/dL) have portal hypertension and usually are responsive to diuretic therapy measures [8].
1.1. First-line treatment
One of the most important steps in treating ascites in this setting is to treat the underlying liver disease. In patients with alcoholic liver disease, abstinence from alcohol intake can result in dramatic improvement in the reversible component of alcoholic liver disease. This measure alone can lead to an around 75% 3-year survival. If the patient does not succeed in refraining from alcohol intake, they may die within 3 years [9]. Abstinence from alcohol intake alone may lead to either complete resolution of ascites or at least a better response to medical therapy.
Ascites in decompensated hepatitis B virus infection-related cirrhosis and autoimmune hepatitis can also have a great response to specific drug therapy, although liver disease is unlikely to be revisable by the time ascites is manifested (Table 2) [10].
High SAAG ascites (>1.1)
Low SAAG ascites (<1.1)
Liver cirrhosis
Tuberculosis
Budd-Chiari syndrome
Malignancy
Sinusoidal obstructive syndrome
Pancreatic
Heart failure (high protein)
Renal
Alcoholic hepatitis
Serositis
Acute liver failure
Table 1.
Causes of ascites.
Treatment of ascites due to liver cirrhosis
1. Treatment of the underlying cause: stop alcohol, treat AIH, and HBV
2. Low-salt diet and diuretics
3. Water restriction if sodium <120 mmol
4. Vaptans (not effective)
5. Albumin and colloid replacement
6. Avoid nephrotoxic medications
Table 2.
Treatment of ascites due to liver cirrhosis.
2. Diet and diuretics
The first-line treatment of patients with cirrhosis and ascites includes (1) dietary sodium restriction (2000 mg/day [88 mmol/day]) and (2) oral diuretics [11]. Evidence suggests that renal sodium retention in these patients is mainly caused by increased proximal as well as distal tubular sodium reabsorption instead of reduction of filtered sodium load [12, 13]. Although the mechanism by which enhanced proximal tubular reabsorption of sodium occurs has not been fully established, the increased reabsorption of sodium along the distal tubule is mainly due to hyperaldosteronism [14]. Therefore, aldosterone antagonists are considered the treatment of choice and are more effective than loop diuretics. Amiloride (with doses of 10–40 mg/day), a diuretic acting in the collecting duct, is less effective than the active metabolite spironolactone and much more expensive and should be used as an alternative only in those patients who develop side effects with aldosterone antagonists (e.g., tender gynecomastia) [15]. There has been a long argument, whether aldosterone should be administered alone or coupled with loop diuretics. Two studies have assessed both approaches. The first used aldosterone antagonists in a stepwise increase every 7 days (up to 400 mg/day) in combination with furosemide (40–160 mg/day, in 40 mg/day steps) considered only in patients not exhibiting proper response to maximum doses of aldosterone antagonists versus joint treatment of aldosterone antagonists and furosemide from the commencement of treatment (100 in addition to 40 mg/day with the option to build the dose in a stepwise manner every 7 days in view of lack of response up to 400 and 160 mg/day) [16, 17]. The results of the two studies were inconsistent with each other probably due to differences in patient populations, in particular, with regard to the percentage of patients with the first episode of ascites [17]. Initiation of both drugs appears to be the favored approach in attaining quick natriuresis and preserving normokalemia. Single morning dosing enhances adherence. Dosing more than once daily decreases adherence and may lead to nocturia.
The maximum doses are 400 mg/day of spironolactone and 160 mg/day of furosemide [8, 11]. Furosemide can be suspended for a short period of time in patients with hypokalemia, which is very common in the setting of alcoholic hepatitis.
Other diuretics including triamterene, metolazone, and hydrochlorothiazide have also been used to treat ascites [11].
Eplerenone is a newer aldosterone antagonist that has been used in heart failure [18]. There is only one study evaluating the use of eplerenone in ascites with comparable results to aldactone [19]. It could also serve as substitute of spironolactone in patients who develop tender gynecomastia [20].
Other loop diuretics, such as torasemide and bumetanide, are currently not being used as they did not seem to demonstrate superiority to the current agents, let alone their cost.
It’s important to mention though, in all patients, diuretic therapy should aim to achieve weight loss of no more than 0.5 kg/day if peripheral edema is absent and 1 kg/day in those with peripheral edema to avoid diuretic-related renal failure and/or hyponatremia which is mainly due to intravascular volume depletion [7]. Other complications of diuretic therapy include hepatic encephalopathy, electrolyte disorders, gynaecomastia, and muscle cramps [13, 21–37]. If cramps are severe, diuretic dose should be decreased or stopped, and albumin infusion [37], baclofen, and l-carnitine may relieve symptoms [23–27, 37].
3. Fluid restriction
Fluid restriction is not necessary in treating most patients with cirrhosis and ascites unless sodium is less than 120. The chronic hyponatremia commonly observed in cirrhotic ascites patients is occasionally fatal if not corrected. One study with 997 cirrhotic patients with ascites showed that the serum sodium is ≤120 mmol/L in 1.2% of the patients and ≤ 125 mmol/L in only 5.7%. Rapidly correcting serum sodium with hypertonic saline in this setting makes the patients prone to more complications rather than the hyponatremia itself.
4. Vaptans
Vaptans are “vasopressin receptor antagonists” and have been studied, mainly in heart failure and in the setting of cirrhosis [38, 39]. Their value in treating hyponatremia and in reducing fluid overload has been investigated. They appear to be useful in treating mild hyponatremia. However, correction of hyponatremia solely may not associate with more important clinical outcomes. The intravenous agent conivaptan has been approved for use for treatment of euvolemic and hypervolemic hyponatremia in hospitalized patients [38]. The manufacturer advises clinician to exercise extra precaution as rapid correction of hyponatremia can have serious/irreversible clinical outcomes, i.e., central pontine myelinolysis. An oral formulation—tolvaptan—increases serum sodium in patients who have baseline values of <130 mmol/L [40]. Of note, correction of sodium is not permanent, and hyponatremia may return when medication is stopped [41].
Recently, satavaptan was particularly investigated to define its effectiveness in managing ascites rather than hyponatremia, was found to be “not clinically beneficial” in the controlling of ascites in cirrhosis, and was linked with higher mortality compared to placebo [42]. It is also more expensive than first-line therapy.
5. Intravenous albumin
An open-label, randomized controlled trial in patients with new onset ascites demonstrates that weekly 25 g infusions of albumin for 1 year followed by infusions every 2 weeks improved survival and decreased the risk of ascite recurrence compared to diuretics alone [43].
In patients who undergo large-volume paracentesis (LVP) > 5 L secondary to refractory ascites, the administration of albumin prevents post-paracentesis circulatory dysfunction (PPCD) [44]. Circulatory homeostasis has detrimental effects in cirrhotic patients as it leads to rapid re-buildup of ascites [45]. Around 20% of these patients develop dilutional hyponatremia secondary to hepatorenal syndrome and/or water retention. The portal pressure usually rises in patients developing circulatory dysfunction after LVP, probably due to a raised intrahepatic resistance due to the action of vasoconstrictor systems on the hepatic vascular bed [46–54]. Finally and most importantly, circulatory dysfunction is usually linked to decreased survival [44, 53].
LVP coupled with albumin infusion is more effective than diuretics and significantly cuts the length of hospital stay. It also has lower frequency of hyponatremia, renal impairment, and hepatic encephalopathy when compared with diuretics. However, there were no differences between the two approaches with respect to hospital readmission or survival [45, 55].
Albumin has shown to be more effective than dextran-70 and polygeline (other plasma expanders) for the stoppage of PPCD [44]. If <5 L of ascites are eliminated, dextran-70 (8 g/L of ascites removed) and polygeline (150 mL/L of ascites removed) show effectiveness comparable to that of albumin. Nevertheless, albumin has higher efficacy than these other plasma expanders if in the case of removal of more than 5 L of ascetic fluid [44]. In spite of that, randomized trials did not show survival advantage in patients treated with albumin versus those treated with other plasma expanders [44, 53, 56]. To demonstrate survival benefit of albumin, larger trials are warranted. Of note, a published meta-analysis included 17 trials involving 1225 patients, demonstrating a lessening in mortality with an odds ratio of death of 0.64 (95% CI, 0.41–0.98) in the albumin group [57, 58]. Albumin was superior to other plasma expanders in which a mean volume of ascetic fluid removed was 5.5–15.9 L [58]. Studies have administered between 5 and 10 g of albumin per liter of fluid removed; 6–8 g/L have been the most frequently used doses [58]. Another study compared albumin doses in 70 patients; the 4 g/L group had comparable PPCD and renal impairment to the 8 g/L group [46, 59].
Albumin is usually infused throughout and/or shortly after the paracentesis. In Europe, only a 20% intravenous solution is available. While in the United States, 5% and 25% intravenous solutions are available, all are isotonic. Using the 5% solution increases the sodium load five times.
6. Drugs to be avoided or used with caution
Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers should be avoided in patients with cirrhosis and ascites even in low doses as they can induce arterial hypotension and renal failure [60, 61]. If used, blood pressure and renal function must be monitored carefully [7].
The administration of nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, ibuprofen, and aspirin, in patients with cirrhosis and ascites is associated with a high risk of development of acute renal failure and hyponatremia and lowers the effect of diuretics [7]. This occurs primarily due to inhibition of renal prostaglandin synthesis leading to deficiency in glomerular filtration rate, which is due to a reduced renal perfusion [62]. Cyclooxygenase-2 (COX-2) inhibitors may provide an alternative for short term as preliminary data show that short-term administration of celecoxib does not impair renal function and does not alter response to diuretics [62].
Beta-blockers have been shown to reduce survival in patients with refractory ascites [63, 64]. This has been linked to their undesirable effect on blood pressure and the increase in the rate of paracentesis-induced circulatory dysfunction [63, 64].
Both blood pressure and renal function should be monitored closely in patients who have refractory ascites with consideration not to initiate or discontinue beta-blockers in such setting.
7. Colloid replacement
Colloid replacement therapy remains as a contentious issue in therapeutic paracentesis. One study compared the use of albumin (10 g/L of fluid removed) versus no albumin in 105 patients with tense ascites, following therapeutic paracentesis [65]. The no-albumin group had statistically significantly more changes in electrolytes, plasma renin, and serum creatinine, but no more clinical morbidity or mortality compared to the albumin group [65]. There are no studies that demonstrate decreased survival in patients without plasma expander compared to patients given with albumin after paracentesis [44].
Polygeline (plasma expander) is no longer used in many countries because of the possible risk of transmission of prions. Some evidence suggest that the use of saline is not linked to a high risk to develop PPCD after small-volume paracentesis [53]; there are no randomized controlled studies comparing saline versus albumin in patients who require paracentesis of less than 5 L. The use of starch as a plasma expander has been addressed in few studies in patients with cirrhosis and grade 3 ascites treated with LVP, revealing some concerning issues regarding the likelihood for starch to induce renal failure and hepatic accumulation of starch [66, 67].
On the other hand, a health economic analysis model suggested that it is more cost-effective to use albumin after LVP compared with alternative cheaper plasma volume expanders. This finding was mainly attributed to the fact that the administration of albumin post-paracentesis is associated with a smaller number of liver-related complications within the first 30 days which leads to increased total health cost [56].
8. Other treatment options
Activation of neurohumoral systems with sodium and water retention plays a major role in the pathogenesis of refractory ascites; thus, drugs that may improve circulatory and renal function, principally vasoconstrictors, have been investigated. Vasoconstrictors such as the α1-adrenergic agonist midodrine or terlipressin improve circulatory and renal function in patients with and without refractory ascites. Terlipressin is given in intravenous boluses (1 mg at onset of paracentesis, 1 mg at 8 h and 1 mg at 16 h) in addition to oral midodrine (for 72 h post-paracentesis), which appear to be as good as albumin in suppressing plasma renin elevation in randomized trials; terlipressin is not commercially offered in the United States [51, 68, 69].
9. Spontaneous bacterial peritonitis (SBP)
Ascitic fluid infection is common (12% in older series) and is associated with mortality rate that surpassed 90% [70–72]. This mortality rate can be reduced to 20% with early diagnosis and treatment [6, 73]. The diagnosis of spontaneous bacterial peritonitis (SBP) is made in the presence of raised ascitic fluid absolute polymorphonuclear leukocyte (PMN) count (i.e., ≥250 cells/mm3 [0.25 × 109/L]). Treatment of SBP is a separate topic; we will discuss the importance of albumin and other therapies in addition to antibiotic use.
10. Empiric treatment
Empiric antibiotic therapy should be initiated in patients with ascitic fluid PMN counts greater than or equal to 250 cells/mm3 (0.25 × 109/L). About 60% of the patients present with culture-negative ascites. If cultures are positive, however, the most common pathogens include Gram-negative bacteria (GNB), usually Escherichia coli and Gram-positive cocci (mainly streptococcus species and enterococci) [71, 74]. The epidemiology of bacterial infections differs between community-acquired (in which GNB infections predominate) and nosocomial infections (in which Gram-positive infections predominate).
Moderately broad-spectrum therapy is necessary in patients with suspected ascitic fluid infection unless otherwise indicated by culture and sensitivity when available. In a controlled trial, cefotaxime, a cephalosporin from the third generation, is shown to be superior to ampicillin plus tobramycin [75]. Cefotaxime or a similar third-generation cephalosporin seems to be the best therapeutic option for anticipated SBP; it is used to cover 95% of the flora including the three most common isolates: E. coli, Klebsiella pneumoniae, and Streptococcus pneumoniae [75]; usually, a 5-day treatment is as effective as 10 days in the treatment [76]. To achieve ascetic fluid levels that are 20-fold above the killing power after 1 dose of cefotaxime, 2 g intravenously every 8 h is required [77]. In neutrocytic ascites, a 5-day course of ceftriaxone 1 g intravenously twice per day was sufficient in treating culture-negative ascites [78].
Amoxicillin/clavulanic acid, intravenously and then orally, has comparable outcomes with respect to SBP resolution and mortality, compared with cefotaxime [79] and at reduced cost.
Another antibiotic that produces a similar SBP resolution rate and hospital survival compared with cefotaxime is ciprofloxacin. Ciprofloxacin is administered as either for 7 days intravenously or for 2 days intravenously followed by 5 days orally. Nevertheless, the cost is higher compared with cephalosporin-based options [80]. However, the use of intravenous antibiotic at the start, followed by oral step-down administration with ciprofloxacin, is more cost-effective than intravenous cefotaxime [81]. Ofloxacin also has produced similar results to intravenous cefotaxime when given orally in uncomplicated SBP, without renal failure, hepatic encephalopathy, gastrointestinal bleeding, ileus, or shock [82].
It is important to mention that, if ascitic fluid neutrophil count does not decrease to less than 25% of the pretreatment value after 48 h of antibiotic treatment, there is a high likelihood of failure to respond to therapy [83, 84]. In such scenarios antibiotic therapy should be broaden to cover more resistant pathogens.
11. Secondary prophylaxis of spontaneous bacterial peritonitis
The ideal prophylactic agent should be safe, affordable, and effective at decreasing the episodes of SBP while preserving the protective anaerobic flora (selective intestinal decontamination) [73]. Given the high cost and the risk of developing resistant organisms, the use of prophylactic antibiotics must be strictly restricted to patients with the following risk factors: (1) patients with acute gastrointestinal hemorrhage, (2) patients with low total protein content in ascitic fluid and no prior history of SBP (primary prophylaxis), and (3) patients with a previous history of SBP (secondary prophylaxis).
The cumulative recurrence rate at 1 year is approximately 70% in patients who survive an episode of SBP with survival rate of up to 30–50% and falls to 25–30% at 2 years [73]. Several antimicrobial regimens have been proposed as secondary prophylaxis. Norfloxacin was studied in a randomized, double-blind, placebo-controlled trial of (400 mg/day orally) in patients who had a previous episode of SBP [85, 86]. Norfloxacin was found to reduce the likelihood of SBP recurrence from 68 to 20% and the likelihood of SBP due to Gram-negative bacteria from 60 to 3%. Other studies evaluated the impact of ciprofloxacin, trimethoprim-sulfamethoxazole, and norfloxacin on SBP recurrence, but they included patients with and without previous episodes of SBP. All studies showed a reduced incidence of SBP with antibiotic prophylaxis [87–89].
The emergence of resistant, extended-spectrum Β-lactamase-producing Enterobacteriaceae has occurred as a result of the extensive use of quinolones to prevent SBP [90–92].
Alternatively, ofloxacin, dosed at 400 mg bid for about 8 days, was found to be as good as parenteral cefotaxime in the treatment of SBP in patients without vomiting, shock, grade II (or higher) hepatic encephalopathy, or serum creatinine greater than 3 mg/dL [82]. A more cost-effective choice when compared to intravenous ceftazidime in a randomized trial would be the administration of intravenous ciprofloxacin followed by oral administration in patients who had not received quinolone prophylaxis [93]. Patients’ flora may become resistant to quinolone prophylaxis, and hence treatment with alternative agents is warranted.
Reduction in mortality was reported in one trial when patients with SBP were randomized to receive cefotaxime alone versus cefotaxime plus 1.5 g albumin per kg body weight within 6 h of enrollment and 1.0 g/kg on day 3. A reduction in mortality from 29 to 10% was described [93]. Another study has revealed that albumin must be administered when the serum creatinine is >1 mg/dL, total bilirubin >4 mg/dL, or blood urea nitrogen >30 mg/dL. If the patient does not meet these prerequisite criteria, then albumin is not indicated [94–97]. Albumin is superior to hydroxyethyl starch in spontaneous bacterial peritonitis [98].
\n',keywords:"ascites, treatment, pharmacological therapy, liver cirrhosis",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/56804.pdf",chapterXML:"https://mts.intechopen.com/source/xml/56804.xml",downloadPdfUrl:"/chapter/pdf-download/56804",previewPdfUrl:"/chapter/pdf-preview/56804",totalDownloads:1198,totalViews:425,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:0,impactScore:0,impactScorePercentile:10,impactScoreQuartile:1,hasAltmetrics:0,dateSubmitted:"February 26th 2017",dateReviewed:"August 8th 2017",datePrePublished:null,datePublished:"November 29th 2017",dateFinished:"August 29th 2017",readingETA:"0",abstract:"Ascites refer to accumulation of fluids in the peritoneal cavity. Ascites is caused by multiple causes, among which liver cirrhosis is the commonest. Confirming the etiology is the first and most important step toward proper management. Assuming that ascites is always caused by cirrhosis can lead to unnecessarily sending patients with different etiologies for liver transplantation, particularly patients with non-cirrhotic portal hypertension. Calculating serum albumin ascitic gradient is important in differentiating ascites due to portal hypertension from other etiologies. The first-line therapy for ascites in cirrhosis is low salt diet and diuretics. It is important to avoid nonsteroidal anti-inflammatory drugs (NSAIDs) and nephrotoxic medications in these patients.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/56804",risUrl:"/chapter/ris/56804",book:{id:"6061",slug:"ascites-physiopathology-treatment-complications-and-prognosis"},signatures:"Aziza Ajlan, Waleed K. Al-hamoudi and Hussein Elsiesy",authors:[{id:"188636",title:"Dr.",name:"Hussien",middleName:null,surname:"Elsiesy",fullName:"Hussien Elsiesy",slug:"hussien-elsiesy",email:"helsiesy@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Alfaisal University",institutionURL:null,country:{name:"Saudi Arabia"}}},{id:"189855",title:"Prof.",name:"Waleed",middleName:null,surname:"Al-Hamoudi",fullName:"Waleed Al-Hamoudi",slug:"waleed-al-hamoudi",email:"walhamoudi@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"King Saud University",institutionURL:null,country:{name:"Saudi Arabia"}}},{id:"207151",title:"Dr.",name:"Aziza",middleName:null,surname:"Ajlan",fullName:"Aziza Ajlan",slug:"aziza-ajlan",email:"aajlan@kfshrc.edu.sa",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_1_2",title:"1.1. First-line treatment",level:"2"},{id:"sec_3",title:"2. Diet and diuretics",level:"1"},{id:"sec_4",title:"3. Fluid restriction",level:"1"},{id:"sec_5",title:"4. Vaptans",level:"1"},{id:"sec_6",title:"5. Intravenous albumin",level:"1"},{id:"sec_7",title:"6. Drugs to be avoided or used with caution",level:"1"},{id:"sec_8",title:"7. Colloid replacement",level:"1"},{id:"sec_9",title:"8. Other treatment options",level:"1"},{id:"sec_10",title:"9. Spontaneous bacterial peritonitis (SBP)",level:"1"},{id:"sec_11",title:"10. Empiric treatment",level:"1"},{id:"sec_12",title:"11. Secondary prophylaxis of spontaneous bacterial peritonitis",level:"1"}],chapterReferences:[{id:"B1",body:'Asrani SK, Larson JJ, Yawn B, Therneau TM, Kim WR. Underestimation of liver-related mortality in the United States. 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Hepatology. 2012;55(5):1551-61.'},{id:"B91",body:'Ariza X, Castellote J, Lora-Tamayo J, Girbau A, Salord S, Rota R, et al. Risk factors for resistance to ceftriaxone and its impact on mortality in community, healthcare and nosocomial spontaneous bacterial peritonitis. Journal of Hepatology. 2012;56(4):825-32.'},{id:"B92",body:'Runyon BA. Changing Flora of bacterial infections in patients with cirrhosis. Liver International : Official Journal of the International Association for the Study of the Liver. 2010;30(9):1245-6.'},{id:"B93",body:'Sort P, Navasa M, Arroyo V, Aldeguer X, Planas R, Ruiz-del-Arbol L, et al. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. The New England Journal of Medicine. 1999;341(6):403-9.'},{id:"B94",body:'Verma A, Lalchandani A, Giri R, Agarwal S, Priyadarshi BP. Evaluation of relation between spontaneous bacterial peritonitis and serum ascites albumin gradient as a prognostic risk factor in chronic liver disease. The Journal of the Association of Physicians of India. 2016;64(1):48.'},{id:"B95",body:'Jamtgaard L, Manning SL, Cohn B. Does albumin infusion reduce renal impairment and mortality in patients with spontaneous bacterial peritonitis? Annals of Emergency Medicine. 2016;67(4):458-9.'},{id:"B96",body:'Salerno F, Navickis RJ, Wilkes MM. Albumin infusion improves outcomes of patients with spontaneous bacterial peritonitis: A meta-analysis of randomized trials. Clinical Gastroenterology and Hepatology. 2013;11(2):123-30 e1.'},{id:"B97",body:'Sigal SH, Stanca CM, Fernandez J, Arroyo V, Navasa M. Restricted use of albumin for spontaneous bacterial peritonitis. Gut. 2007;56(4):597-9.'},{id:"B98",body:'Grange JD, Amiot X. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. Gastroentérologie Clinique et Biologique. 2000;24(3):378-9.'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Aziza Ajlan",address:null,affiliation:'
Department of Pharmacy, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
'},{corresp:null,contributorFullName:"Waleed K. Al-hamoudi",address:null,affiliation:'
Department of Liver Transplantation, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
Division of Gastroenterology, King Saud University, Riyadh, Saudi Arabia
Department of Liver Transplantation, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
Department of Medicine, Alfaisal University, Riyadh, Saudi Arabia
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1. Introduction
Imagine a deaf patient who lost her outer, middle, and inner ears through disease or injury. The remaining parts of her auditory pathway (cochlear nerve, cochlear nucleus, superior olive, lateral lemniscus, inferior colliculus, medial geniculate body, and auditory cortex) are intact. Although profoundly deaf, the patient is not hopeless. She expects us to fit her with two electronic devices that would feed suitable signals to her cochlear nerves, thus allowing her to hear again.
The current cochlear implant devices are exceedingly basic: they normally assist or compensate for certain malfunctions of damaged parts of middle or inner ear (auditory cells, tectorial membrane, etc.) but offer only crude restorative signals spanning approx. 10 channels. To appreciate the inadequacy of the current state-of-the-art, the reader might want to peruse simulations at [1].
In contrast, healthy human cochlear nerve consists of approx. 30,000 neural axons, with almost every axon conveying one channel of a signal. Humans do not hold any records in this regard: feline cochlear nerves contain approx. 50,000 axon fibers. The information traveling through neural axons is digital in nature, due to all-or-nothing neural axon hillock operation when generating signal. No wonder then that the problem of refining cochlear implants catches interest of some computer scientists.
Formation of the complete multi-channel, representative signal adhering to the biological cochlear nerve signal protocol is a daunting task, requiring deep understanding of the workings of outer, middle, and inner ears, which participate in the signal generation process, as well as the workings of organs in the auditory pathway, which receive and interpret these signals. While the functionality of ear organs is relatively well understood, the same cannot be said about the organs higher up the auditory pathway. We shed some light here on their functionality.
The biologists and physicians instill in us the awe for the complexity of biological organs. Ears are such organs. Outer ears are sound channeling and amplification devices, processing sound waves traveling through air. Middle ears are mechanical in nature: their tiny ossicles (malleus, incus, and stapes) controlled by equally tiny muscles amplify weak signals or dampen strong signals before conveying them to inner ear. In this way the inner ear is protected. Finally, inner ears are wonders of electromechanical and electrochemical precision, governed by the laws of fluid dynamics, etc.
Our goal is to build an electronic device creating a fully restorative cochlear signal without entering too deep into details of functionality of biological ears. We argue that our ears are unnecessarily complex for their function. They emerged through the process of evolution, not intelligent design. That evolutionary process consists of introducing random changes into the genotype (via crossover and mutation) and then ensuring of survival of the fittest individuals via natural selection. In this way only deleterious genetic changes are eliminated. Neutral changes are allowed to remain, thus unnecessarily increasing the complexity of emerging systems.
Biological textbooks offer many examples of such unnecessary complications introduced by the evolutionary process: consider the path of laryngeal nerve, allowing the brain to control the larynx. The nerve’s inferior (recurrent) branch, innervating larynx muscles, is unnecessarily long: it descends from the brain into the thorax only then to return to the larynx. In medical textbooks it is frequently cited as an evidence of evolution: in giraffes this extra length can be measured in meters! This feature is a vestige of an evolutionary process—in fish throats and gills are in immediate vicinity so this detour did not exist when fish were the most complex animals.
Another example could be the structure of an eye. Human retina has a blind spot; also, tiny blood vessels supplying blood to the retina are positioned in front of it, rather than behind it, thus occluding some sensory cells (rods and cones). Such clumsy “design blunder” can only evolve through a process of mutations and natural selection. To compensate for that “blunder” the brain’s visual cortex had to evolve unnecessary complexity. We have already decoded the fundamental workings of the visual cortex [2, 3]; here the same methodology is used to attack the problem of signal processing for auditory perception.
The complexity of the central nervous system (CNS) to a large degree is due to existence of structures compensating for its earlier structural inefficiencies. The difficulty in figuring out the inner workings of CNS stems from the fact that the biologists must study with equal diligence all parts of the CNS: those essential and those secondary to its functionality. They have no choice there: to distinguish between the roles of these parts is to understand the CNS functionality.
This multi-disciplinary chapter consists of two parts:
We start by presenting a simplified but functionally complete model of our auditory perception, together with an electronic model of a device capable of providing restorative signal to the cochlear nerve, thus suggesting a new generation of cochlear prostheses. This functional description is targeted at electronic engineers who may have little biological background but will be tasked with creation of electronic circuits producing suitable e-cochlear signals.
Following that we demonstrate mathematically that signals so obtained carry information useful to the healthy part of the auditory pathway to perform the well-understood functions of audio location, as well as the more complex functions of audio pattern recognition and may even give rise to the subjective pleasure of music, so enjoyed by healthy humans. This section is written with some mathematical rigor.
2. The nature of auditory perception
Departing from the traditional phase-based or frequency-based models of cochlear and vestibular signals we offer simpler, unified, and biologically inspired insights that rely on massive parallelism, needed for real time auditory pattern recognition. Our signal analysis is also applicable to vestibular signals, used to balance body equilibrium and posture, as well as to stabilize retinal image.
To justify our approach to auditory perception modeling consider a hare hearing a noise: it uses its audio signal to detect a possible predator approaching, in order to take a prompt evasive action. Our hare uses its auditory pattern recognition skills live, as soon as it starts hearing the noise; this is necessary for hare’s survival.
Luckily for all of us (hares included) the signals we perceive are causal. A signal f(t) is causal, iff
ft=0forallt<0E1
This work deals with causal signals, in the above sense.
To cope with causal signals, we build causal systems. An output y(t0) of a causal system at a given time t0 depends only on its causal input x(t), for all t ≤ t0. We create causal systems by building their causal models first.
The simplest (trivial!) causal system can be modeled as follows:
Given an input signal x(t) for 0 ≤ t ≤ t0, we may create a causal model that copies the input signal to its output, that is, produces y(t) = x(t). A memory-less causal system using such a trivial model is pretty much useless: it cannot understand the signal it processes.
We strive to create systems that use causal models in anticipatory fashion, that is, intending to forecast (within desired accuracy and meeting specific time deadlines) the input signal x(t1) at some future time t1 > t0 on the basis of a known input x(t) for 0 ≤ t ≤ t0. For that we need an intelligent system.
Indeed, this is the essence of intelligence demanded of a system meeting challenges of its environment. A system is intelligent if it is capable of forecasting reliably enough its future causal input signals, while meeting forecasting deadlines. The longer forecast horizon and the better accuracy of prediction, the higher is the intelligence of such a system.
Example: Our hare hearing a noise may estimate the proximity, the direction, and speed of an approaching predator, and then timely identify and execute suitable evasive action. A hare capable of routinely saving its skin in this way is considered intelligent, that is, well adapted to its environment. To be so adapted the hare need not only to be versed in auditory perception, but also capable of real-time execution of its algorithms.
Example: Humans understand and like music. What is it exactly that we like?
When we say that we understand a causal signal we mean that we perceive patterns in it, and, using them, we are capable of building a predictive model of the signal. In this chapter we preoccupy ourselves with audio signals. Some of them we perceive as noise, some of them as music. How can we tell the difference? Or, is there a difference?
Following the logic just presented we say that we understand a particular audio signal, if we can forecast future signal values with satisfactory accuracy within some time horizon. To understand an audio signal means to have a useful model of it. We feel pleasure when we can accomplish this, and term such signal music (or speech, etc.) Other signals are termed noise. Additional pleasure is instinctively drawn from the realization that we are coping successfully with the challenges of our environment, and in particular, when listening to music that we are not in any danger regardless of the success or failure of our predictions; and so, we can hone our predictive skills in complete safety by listening to music, perhaps repeatedly.
Observe further that a previously taped “musical” signal can still be perceived as “noise” if reproduced at modified speed, or perhaps played backwards, thus making real-time forecasting impossible. This reinforces our view that the signal counts only as “music” if we can understand it, that is, identify patterns within it, use these patterns for forecasting its future passages while executing in real time the entire computation of forecasts, before the actual signals arrive. That successful verification of hearing our forecasts coinciding with reality as time advances (within “reasonable” tolerances) we call enjoyment of music or understanding of speech – at least in terms of adherence to relevant grammatical rules.
The larger goals of our research are twofold: (1) to further the understanding of the working of the CNS including human brain and (2) to learn how to build smarter devices, capable of interfacing with our CNS. Here we pursue both goals, using the methodology previously successful in decoding fundamentals of visual signal processing [2, 3]. Drawing on biological inspirations we limit our use of math tools to set theory and theory of metric spaces. After all, even simple animals seem to execute in timely fashion the forecasting models appropriate to their environmental niches. We doubt that simple animals have sufficient computing skills to execute complex math in real-time. In the spirit of Occam’s razor, we value simplicity. Simple models can be executed fast. When it comes to survival, speed counts!
Although the focus of this chapter is on cochlear signal processing, it is worth noting that all nerve signals are similar in structure and this similarity is of immediate practical interest in vestibular nerve signal processing. The vestibular system is responsible for sensing body equilibrium and posture, as well as for stabilizing eyeballs when we move our heads (a Steadicam function) [4, 5, 6, 7].
3. Basic model of auditory perception
For the purposes of this chapter, we would like to offer a simplified engineering model of human auditory perception. At the outset we beg for indulgence of our biologically trained readers: detailed descriptions of this system are available elsewhere [8], including other chapters of this book.
Our description focuses on features of the system in need of further explanation, namely those of interpretation of signals by the auditory cortex. We limit our description of anatomy to essential features only.
The brain’s auditory pathway consists of cochlear nucleus, superior olive, lateral lemniscus, inferior colliculus, medial geniculate body, thalamus, and terminating at auditory cortex.
Vigorous research activity is aimed at understanding the functionality of these brain nuclei by studying their neural structure. We propose a different approach, which we tested successfully when studying the functionality of human vision system [2, 3]. As pointed out already, we are convinced that these brain nuclei are exceedingly complex, as they contain structures essential to their function as well as those merely vestigial to the evolutionary process. To discern between those two kinds is not possible without understanding the functionality of the auditory pathway, which is the very goal of this research effort.
Facing this circular conundrum, we prefer another investigative approach: given the information traveling via cochlear nerve we attempt to deduce the structure and functionality of an abstract computer needed to account for auditory perception we (humans) experience. We depart from the assumption that intelligence must be wet or carbon-based; for us these are just details of a particular implementation. We prefer silicon.
Figure 1 depicts the schematic anatomy of the human ear. We mention in passing the well-known facts: the acoustic signal, that is, the air-pressure wave, traveling through the external auditory canal impedes on tympanic membrane, a.k.a. eardrum, causing it to vibrate.
Figure 1.
Basic anatomy of the human ear.
The tiny bones of the middle ear (malleus, incus, and stapes) convey the mechanical vibrations of the eardrum to the cochlea where the sound perception begins.
The cochlea is a chamber filled with fluids (called perilymph and endolymph), which are in turn induced to vibrate. In engineering terms, the cochlea acts as an attenuating waveguide. It is most permeable to low frequencies, while strongly attenuating high frequencies.
Human ear can at best discern frequencies within the 20 Hz–20 kHz range. Other animals can hear within different frequency ranges, but the principle of operation of their cochleae remains the same: high frequencies are perceived only in the cochlear region close to the stapes, middle frequencies penetrate deeper, but only low frequencies can travel though entire cochlea. This distribution of frequency sensitivity along the length of the cochlea is referred to as tonotopy.
As the cochlear perilymph vibrates, it actuates the auditory cilia, that is, “hairs” of the “hair cells,” which convert these vibrations into electrical signals. These signals are then communicated (via neurotransmitters) to the nerve cells of the cochlear nerve, which passes the signals to the brain.
The hair cells are organized into the organ of Corti, shown in the cochlear cross-section of Figure 2.
Figure 2.
Cochlear cross-section showing the organ of Corti.
We omit here again many details of primary interest to anatomists, while focusing mainly on the cochlear duct called scala media (shown in green in Figure 2). It is filled with endolymph and contains the organ of Corti, attached to the basilar membrane, being one of the walls of scala media.
Organ of Corti contains large number of mechanoreceptors, called auditory cells. Each auditory cell is equipped with 100–150 whiskers, called auditory cilia, all bathed by vibrating endolymph. Some of the longer cilia are attached to the tectorial membrane. Both basilar and tectorial membranes also vibrate with the endolymph.
Figure 3 shows the rudimentary schematics of an auditory cell.
Figure 3.
Rudimentary schematics of an auditory cell.
At resting state (no sound wave) the auditory cell body maintains certain equilibrium, measured in terms of an electrochemical potential of cell body interior. It sends then no signal to its cochlear neuron.
The sound vibrations of the endolymph in scala media impact on the single cilium shown causing it to bend sideways.
Deflection of the cilium in one direction causes excitatory increase of potential inside cell body. When that potential reaches a certain threshold level, called action potential, the cell issues into its synapse a certain amount of a specific neurotransmitter, which in turn causes electric signal to travel through the cochlear neuron.
Deflection of the cilium in opposite direction has inhibitory effect on cell body potential, thus silencing the cell.
In short, responses to vibration of the endolymph in scala media of the organ of Corti cause periodic changes in the potential of the auditory cell, thus causing a series of pulses travel through the axon of a cochlear neuron (i.e., cochlear nerve fiber) associated with that auditory cell.
The cochlear nerve is a bundle of axons of cochlear neurons. Consequently, signals traveling through cochlear nerve constitute simultaneous groups of series of pulses, each series being transmitted sequentially by a particular fiber of the nerve.
Given that the cochlea acts as non-linear waveguide, attenuating various frequencies differently, every place along its length experiences different sound pattern. For the purpose of pattern recognition, it would then be best if a number of mechanoreceptors (hair cells) were placed in exactly the same cochlear location.
However, every hair cell has finite dimensions, so it is impossible to place a number of them in the same location. Nature had no choice but to distribute them along the organ of Corti. No wonder then that different hair cells respond differently to various frequencies. All these cells are anatomically identical; their varying responses result from being exposed to different vibrations of the endolymph in their particular locations. This is the essence of tonotopy.
Nature has done everything possible to reduce the consequences of building the organ of Corti, populated by hair cells, as having non-zero dimensions, by filling the inner ear with liquid. The speed of sound waves in liquids is an order of magnitude higher that in gases. The relationship between the wavelength λ and the sound frequency f is λ = v/f, where v is the speed of sound in each of these media. From this it follows that for a given frequency f the sound wavelength in liquid is much longer than in gas, thus reducing the relative consequence of distribution of hair cells along the organ of Corti. The auditory cilia of these cells vibrate much more in sync when bathed by a liquid than they would if they were in gas. Furthermore, the inner ear is encased in the hardest bone found in a human body. This arrangement maximizes the agitation of cilia, by forcing the liquid to vibrate along the cochlea, and so perpendicularly to the cilia.
High audio acuity requires large numbers of auditory cilia, and so a larger organ of Corti in a longer cochlea. No wonder then that in simpler animals the cochleae are straight, while more complex animals have their cochleae coiled. It all has to do with the problem of packing of an elongated cochlea into a small cranial cavity within an exceptionally hard bone.
Loudness is a subjective quality of sound that is an attribute of auditory perception. We all classify sounds on some scale ranging from “quiet” to “loud.” However, sound experience is a creation of our brain, a correlate with a physical phenomenon (a sound wave) impacting on our ears. Sound waves can be measured in terms of physical values like power, amplitude, frequency, sound pressure, etc.
Given that our eardrums react to sound pressure, it seems logical to correlate loudness with sound pressure. This relationship, depicted in Figure 4, is particularly dependent on frequency. We can easily perceive relatively weak sound waves, as long as their frequencies lie within an interval of 1–4 kHz, this being the predominant frequency range of human speech. Sound waves outside of that interval (both of higher and lower frequencies) must be substantially stronger to be perceived as equally loud. This non-linearity arises due to the inertia of the mechanical parts of our ears (eardrums, malleus, incus, and stapes) as well as the inertia and drag of the auditory cilia against the surrounding liquid. Our novel cochlear prostheses need to account for all these nonlinearities.
Figure 4.
Contours of equal loudness (red) as functions of frequency (Hz), ISO 226:2003 revision. Older ISO standard for 40-phon shown in blue.
To outline our modeling methodology, consider an arbitrary signal (shown in blue), traveling through endolymph and impacting on an auditory cilium of a hair cell, depicted in Figure 5.
Figure 5.
Hair cell with action potential ap = 0.25 inscribes a square-wave signal (red) within a sample pressure wave (blue) of an endolymph.
That cell has an action potential ap = 0.25 units and generates a packet of rectangular pulses (shown in red) inscribed within the endolymph pressure wave as observed at the cell location. Its neighboring cells may have action potentials set at different values, and together they describe the pressure wave with some accuracy. Note that this description is not exact, as one would need (mathematically speaking) an infinite number of cells at the very same location in scala media, all with different action potentials (forming a continuum) to describe the signal exactly. In that sense the pressure wave could be seen as curve enveloping all possible inscribed square pulse signals.
The illustration in Figure 5 depicts a wave of sufficiently low frequency, so that the relevant auditory cell is able to inscribe a square pulse into each peak of the audio wave. Not all audio cells are capable of such behavior. Due to their inertia, they need time to adjust their electrochemical potential levels. An inhibited call will need more time to bring its potential to the action level than a cell that was in a neutral state. After firing a pulse each cell requires certain amount of time to bring itself into the state of readiness to fire again.
The net result of this is that the cells do not always faithfully inscribe their pulses into the acoustic wave, although the firing of their pulses is stimulated by that wave. The inertia of all cells is similar and so they generate pulses of similar frequency characteristics. It is their location in the cochlea and their connections to relevant axons of the cochlear nerve that causes us to perceive varying pitch.
The emerging bundle of signals formed in this way, traveling along the cochlear nerve, carries to the auditory cortex the information about the ambient sound wave.
Specifically, there is only a finite number of cells with different action potentials in a particular region. That region being small, we can assume that all of them respond in sync to the same pressure wave. Our model deals therefore with bundles of square pulse approximations of the sound wave. According to the Shannon-Hartley theorem [9, 10] these approximations can be still exact even for a finite number of hair cells used, provided that their stimulating signal lies within certain harmonic limitations.
The frequency region of 20 Hz–20 kHz is not such limitation, as it only describes limits of the audible frequency response curve for human hair cells. Acoustic signals outside this range are merely inaudible but they do exist. Certainly, some harmonic limitations of an acoustic signal exist. Given that wave energy is proportional to the wave frequency, there must be some limit to the number of frequency components of a given audio signal for the signal to carry finite energy. We inhabit a universe filled with signals of finite energies—because of that we can exist.
Let us take a closer look at square pulse signals of finite length. There is a number of possible descriptions of a signal s(t) consisting of n pulses:
st=<t0,t1,t2,t3,…t2n−1>E2
where < •, •, … • > is a tuple of 2n values listed in strictly ascending order, that is, for every pair of values ti, tk such that i < k we have ti < tk. The time values with an even index define the beginning of a pulse, the times with odd index represent the end of a pulse.
Alternatively, we can represent signal s(t) as a set of mutually exclusive time-line intervals:
st=t0t1t2t3…tn−2tn−1E3
Using this description signal values for arbitrary t can be calculated as follows:
In fact, we will deal mostly with normalized signals, that is, assuming values 0 and 1. Such signals can be obtained by dividing the above pulse signal by its action potential, viz. s(t)/ap yielding:
Alternatively, having defined a function step(t) as
stept=0fort<0;1otherwise,E6
we may describe a normalized signal s(t) as:
st=∑i=02n−1−1i∗stept−tiE7
Observe that whatever the signal descriptions—Boolean algebra applies to normalized signals.
Let as label as true the value 1 of a normalized signal, and as false its value 0. Then, given two arbitrary normalized signals f(t) and g(t), possibly consisting of a different number of pulses of arbitrary timing, we can define standard Boolean operations as follows:
notft=stept–ftE8
ftandgt=ft∗gt,and finallyE9
ftorgt=ft+gt−ft∗gtE10
These definitions allow us to formulate:
3.1 Self-test procedures for cochlear prostheses
Consider two arbitrary normalized signals f(t) and g(t), generated by two artificial hair cells of opposite orientation but of the same action potential and belonging to the same cochlear neighborhood. By opposite orientation we mean that both of them cannot be excitated simultaneously. For properly functioning such pair of artificial hair cells of a cochlear prosthesis the following conditions must hold for every t:
ftandgt=0ftand notgt=ftgtand notft=gtE11
This is so because f(t) and g(t) are mutually exclusive signals, while neither of them is the pure negation of another.
These test conditions can also be used to test cochlear prostheses as well as for hearing loss due to the loss of auditory cilia, caused by exposure to exceedingly high sound levels. Human hair cells have many cilia and initial hearing loss is usually not noticeable until large numbers of cilia are lost.
3.2 Audio location using pulse signals
Our simple methodology is sufficient for description of tasks like audio location.
Consider two hair cells with the same action potential, housed by two cochleae in two ears of an animal. A sound wave excites both cells, as per Figure 6.
Figure 6.
Audio location process: One of two auditory cells in two different ears detects the same signal with a bit of delay.
An animal is capable of estimating the azimuth of the audio source by calculating the angle (shown) of the incoming sound. The essence of this well understood process is as follows: two hair cells, located in two cochleae of an animal are not excited simultaneously by an arriving sound wave. The delay in excitation of the hair cell more distant from the sound source can be used to calculate the extra distance the sound wave must travel to reach that cell (shown in Figure 6) Given that the base distance between the two cells (also shown in Figure 6) is an anatomical constant for a given animal, and the speed of sound in the medium the animal inhabits is also constant, then the angle of arrival of the sound wave can be calculated from the right triangle shown. In fact, an audio locating animal does not need to perform those complex trigonometric calculations. It just needs to turn its head to make both signals arrive simultaneously: it then faces in the direction of the incoming sound.
Observe further that for this method to work the length of the sound wave cannot be too long nor too short. Too long waves would not result in contrasting deflections of the corresponding cilia; for to short waves the uniqueness of the solution is lost (due to the periodic nature of the oscillations).
Optimal locating acuity occurs when the deflections of the cilia are of opposite phase. That is why the optimal sound wavelengths ensuring this remain in close correlation with the distance between two corresponding cells located within two ears of an animal. This explains why humans use frequencies much lower than bats, for example. It all has to do with different distances between ears of humans and bats. The square pulse nature of the signals generated by the hair cells enhances contrast between these signals, thus facilitating the audio location process.
The above examples are intended to demonstrate the capability of our approach to model processes already well understood. To gain understanding of more complex processes of audio pattern recognition, music, etc. we need to introduce several new concepts. We start with the design of the prosthetic device.
4. The cochlear model and prosthetic device
Our concept of a modular multi-channel device allows the number of supported channels to grow arbitrarily as technology advances. According to current practice, the device consists of two parts: the implantable part and the external part, worn by the patient. This is in order to maintain skin continuity thus avoiding infection. Both parts communicate via a trans-dermal electromagnetic link.
The external part is responsible for the formation of the multi-channel restorative signal and for transmission of the multiplexed signal via the electromagnetic link to the implantable part. The implantable part de-multiplexes the received signal and feeds proper channel signals to the relevant fibers of the cochlear nerve via a micro-array of tiny electrodes. The technological challenges of connecting microscopic multi-channel cables to proper fibers of a nerve are currently being addresses by work of several teams, led by Charles C. Della Santina at Johns Hopkins University (Vestibular Neuroengineering Lab), Daniel Merfeld, Wangsong Gong, and Richard Lewis at Massachusetts Eye and Ear Infirmary (MEEI) in Boston, James O. Phillips of the University of Washington, Andrei M. Shkel at the University of California, Irvine, Julius Georgiou at the University of Cyprus, and elsewhere [4]. Although these expert teams focus their work on the vestibular nerve, the technological challenges of connecting a micro-array of electrodes to any nerve remain the same.
In fact, we can use the cochlear nerve fiber layout to facilitate the connection. Figure 7 shows the cochlea and the outgoing nerve fibers. Observe that due to the spiral nature of the cochlea the central fibers of the nerve are connected to the cochlear tip and so are responsible for conveying information about low frequency components of the audio signal, while the outer fibers deal with high frequency components. Connection of a micro-array of electrodes to the nerve can therefore be a two-step procedure. First, we attach a micro-connector configured so that its center wires mate with center fibers, and then we fine-tune the connection by creating a detailed connection map, customized to each patient. We do that by passing stimulation signals to individual wires while asking the patient about frequencies perceived.
Figure 7.
Cochlear nerve layout: center fibers convey information regarding low frequency components of the audio signal; perimeter fibers deal with high frequencies.
We focus now our attention on the formation of the restorative signal by an electronic device. That device consists of a microphone of a suitable directional characteristic, worn by the patient close to his non-functional ear, a transducer ensuring the transdermal connection, and a small electronic box, containing analog and digital circuitry.
To simulate our patient’s cochlea, we will turn to the time-tested technology: that of a telegraph line. Early telegraph operators noticed that long telegraph lines tend to distort signals generated by telegraph keys. On the receiving end square pulse signals tended to have their edges rounded. When the line was too long, this distortion made the received signal unintelligible: dots of the Morse code would disappear, while dashes became dots with gentle slopes. To avoid this, telegraph lines have had certain maximum length, beyond which “repeaters” were used to refresh the signal. Early repeaters were just people transcribing the signals, later replaced by electrical devices.
While the goal of telegraph line builders was to maximize the quality of the signal and thus to maximize distance between repeaters by minimizing distortion, our goal is to minimize the size of the “bionic ear” worn by the patient. To that end we will construct a model of a bad telegraph line distorting the signal over short distances, and we will not use any repeaters.
A circuit shown in Figure 8 is a model of a telegraph line segment or of neural axon segment. The wires of this segment present certain electrical resistance R [measured in ohms] and given that such line is never perfectly straight, a certain inductance L [henries]. The insulator between the two wires (air, plastic, etc.) is never perfect and so has a certain conductance G [siemens], and, together with the wires offers certain capacitance C [farads].
Figure 8.
Electrical model of a segment of a telegraph line or of a “bionic cochlea.”
In physics the concepts of conductance G and resistance R are bound by an inverse relationship: G = 1/R. In the circuit of Figure 8 the values of G and R are unrelated; they are just intrinsic parameters of a line segment.
Such circuit distorts an input signal applied to its left terminals by selectively attenuating harmonic components of the signal: higher harmonics are attenuated more than the lower harmonics. A telegraph line or our “bionic cochlea” nerve fiber can be represented by a finite sequence of such segments, as per Figure 9.
Figure 9.
Electrical model of a telegraph line or of a “bionic cochlea.”
In a real cochlea information contained in higher harmonics of a signal is gathered close to the entry of the cochlea (i.e., close to the oval window), while only lower frequencies can penetrate to the end of the cochlea. The cochlea has a special terminator (called round window). That terminator has a dual role.
First, it allows the non-compressive endolymph, encased in a very hard bone, to move along the cochlea, thus agitating the auditory cilia. Indeed, in certain congenital abnormalities the round window may be missing or rigidly fixed. Not surprisingly, people so affected suffer a huge hearing loss of about 60 dB.
In a healthy cochlea, low frequency endolymph movements do not cause slowly moving liquid to exert sufficient drag on the cilia (it is analogous to the ease of moving a paddle through water sufficiently slowly). This translates to lowering of auditory sensitivity as frequency decreases, shown in Figure 4. On the other side of the audible frequency spectrum, high frequency waves are of small amplitude, and, attenuated further by the cilial inertia similarly fail to sufficiently deflect cilia, again resulting in loss of sensitivity as per Figure 4.
Second: The round window prevents sound waves from bouncing off the end of the cochlea and traveling back towards the oval window. Should this happen interference or even standing waves could form in the cochlea, resulting in humans hearing subjective sounds in absence of external stimuli (a condition known as tinnitus). A healthy cochlea is an echoless chamber.
Following those anatomical hints, we will sample signal in various points along our e-cochlea. This e-cochlea should be echoless, too. If it were infinitely long, it would certainly be echoless, as the signal could never reach its end to bounce back. This is impractical, though.
We can, however, calculate the input impedance of an infinitely long circuit depicted in Figure 9. Let that impedance be Z. If we terminate a finite circuit shown in Figure 9 with a terminator Z (not shown), then viewed from the input side that circuit will be indistinguishable from an infinitely long circuit, and so will become echoless.
Incidentally, nature followed the same process when evolving cochleae. To increase audio acuity of more complex animals, it had to sample signals in many places along a cochlea, so the cochleae of higher animals had to become longer. In order then to fit them into a limited space of a cranial cavity in an extraordinarily hard bone the cochleae had to be coiled. Coiling a cochlea does not affect it acoustic properties much as coiling of a trumpet makes a trumpet smaller but does not affect its sound. With the exception of monotremes, all mammals have coiled cochleae.
We are now in a position to present the fundamental circuitry of our “bionic ear,” as per Figure 10. The electric equivalent of an audio signal (for brevity called “audio signal” henceforth) is fed into an e-cochlea made of a large but finite number of segments, and properly terminated by an echoless terminator Z (not shown).
Figure 10.
Electrical model of a “bionic ear”: each segment of the e-cochlea generates one digital signal.
The input audio signal fed to each segment is also input to an analog sampling circuit equipped with a basic A/D converter. The output of this converter is true when its input voltage is positive and is false otherwise. In this way a pulsating digital signal is obtained. The A/D converter can be constructed from a single transistor oscillating between the cut-off and saturation states or a similar device. It simulates the axon hillock of an auditory neuron.
Given that on short time scales the audio signal is practically symmetric about the timeline, only the signal values exceeding certain positive reference voltages need be sampled. Every reference voltage is determined by the ratio of resistances R1/R2. When the voltage of the audio signal exceeds that threshold value, then the diode depicted in the diagram charges the capacitor Cx. As long as this capacitor is sufficiently charged, the A/D converter outputs the value true. The resistor Rx slowly discharges the capacitor Cx. A careful choice of the decay time constant RxCx, customizable to each patient, controls the minimum duration of each pulse. That time constant describes the dynamics of an auditory cell changing its electrochemical potential.
Similarly, by adjusting values of the threshold ratio R1/R2 in each segment we can control the audio sensitivity of our e-cochlea to fit curves shown in Figure 4. Further tweaking is possible to customize this circuitry to the sensitivities and preferences of individual patients.
Note the simplicity of this design: Our “bionic ear” consists of a number of repeating segments, each segment yielding one channel of a digital signal. All segments are topologically identical, but may differ in element values R, L, G, and C to span the desired frequency spectrum in suitable number of steps, yielding the required number of channels. The last segment is capped with a suitable echoless terminator Z.
Due to current technological limitations this design probably does not allow us to create a sequence of 30,000 segments today, each segment generating a pulse signal to feed one fiber of the cochlear nerve, but it certainly overcomes current channel limitations. Furthermore, the modularity of the design allows us to build ever better, multi-channel bionic ears as technology improves.
This concludes our qualitative description of bionic ear electronics. To demonstrate that our device is capable of generating signals useful for sophisticated auditory perception, we need to introduce several mathematical concepts. We will also shed light on the way brain nuclei higher up the auditory pathway operate, with emphasis on audio pattern recognition and classification.
5. Variation on the theme of metric spaces
Mathematicians conceive a metric space as a set of objects, usually called “points,” between which a way of measuring the distance has been defined. In everyday life we use Euclidean distance. However, this is only one of the many possible ways of measuring distances.
Let S be our space of interest.
Definition 1. Measure of distance: Any real-valued function d: S × S → R can be used as a measure of distance, provided that for all x, y, z ∈ S it has the following properties:
The last property is frequently called the triangle law, because the length of each side of a triangle cannot be greater than the sum of lengths of two other sides.
The properties (12) and (13) imply that the distance between any two points cannot be negative and is actually positive if the points are different. In fact, we can state.
Theorem 1: Given any real-valued function d: S × S → R suitable for measuring distances between points in S, the equality d(x, y) = 0 for any x, y ∈ S implies x = y.
Proof: The equality d(x, y) = 0 means that a shortest travel from x to y does not make us cover any distance, therefore x and y must coincide, that is, x = y.■
As examples consider a two-dimensional space R2 and two points a = 〈x1, y1〉 and b = 〈x2, y2〉. We may define distance d(a, b) as:
Euclidean distance:d1ab=sqrtx1–x22+y1–y22orE16
Manhattan distance:d2ab=x1–x2+y1–y2orE17
perhaps simplyas:d3ab=maxx1–x2y1–y2E18
All three functions d1, d2, and d3 meet the necessary requirements (12), (13), (14) and (15).
Definition 2. A metric space is the configuration 〈S, d〉, where S is a set of points, and d is some measure of distance between them.
In our study we are frequently interested in measuring distance between subsets of S, rather than only between points of S. One of the simplest subsets of S is a ball.
Definition 3. A ball of radius r ≥ 0 around the point c ∈ S is the set
x∈Sdcx≤rE19
which we will denote as B(c, r) without mentioning either S or d when confusion can be avoided. The point c is called the center of the ball B.
Note: In older math textbooks the term “sphere” is frequently used instead of a “ball.” This usage is currently being phased out, as we prefer now the “sphere” to mean the surface of a “ball.”
Observe that the “shape” of a ball depends on the way we measure distance, as per Figure 11.
Figure 11.
The balls in R2 of same radius, with center in the origin of the system of coordinates, defined using metrics d1, d2, and d3 in the previous example. Similar balls in R3 would be a sphere, an octahedron, and a cube, correspondingly. Generalizations of balls in higher-dimensional spaces are conceptually straightforward, although not easily drawn.
It is worth noticing that the “volumes” of such balls may depend on the metrics used. In particular, the Manhattan ball d2 is most specific about its center, that is, it has the smallest “volume” (i.e., area in R2), and also its metric function (17) computes faster than metrics (16) and (18). This is important for some of pattern recognition algorithms including visual and auditory perception, which, although fast and massively parallel, remain computationally intensive [2, 3].
A more detailed analysis of metric spaces can be found at [11].
6. Computing distances between sets
Given any two non-empty sets A, B ⊂ S we need to construct a function D(A, B) to measure distance between A and B. That function should retain the properties (12), (13), (14) and (15). In particular, observe that the properties (12) and (13) imply that D(A, B) > 0 even if the sets A, B touch (i.e., have one common element), or intersect, or perhaps one of them contains another (A ⊂ B or B ⊂ A). In fact, we must construct function D such that D(A, B) = 0 if and only if A = B.
Let d be our chosen function for measuring distance between points of space S. We will use this function to construct our function D.
Definition 4. Distance between a point and a set: Let 〈S, d〉 be a metric space and let A ⊂ S be a non-empty set. A distance between a point x ∈ S and A, denoted δ (x, A) is given by
δxA=infdxaa∈AE20
It is the distance between x and a point a ∈ A closest to x. Using δ, let us define.
Definition 5. Pseudo-distance between two sets: Let 〈S, d〉 be a metric space and let A, B ⊂ S be two non-empty sets. A pseudo-distance from A to B, denoted Δ(A, B) is given by
ΔAB=supδaBa∈AE21
In other words, pseudo-distance from A and B is the distance from the most distant point a ∈ A to its closest point b ∈ B. It is not distance, but merely pseudo-distance, because it is unidirectional, that is, the property (14) does not hold, given that Δ(A, B) ≠ Δ(B, A) in general. To make it bidirectional, we define.
Definition 6. Distance between two sets: Let 〈S, d〉 be a metric space and let A, B ⊂ S be two non-empty sets. A distance between A and B, denoted D(A, B) is given by
DAB=maxΔABΔBAE22
We are ready now to demonstrate that our construction of D(A, B) has properties of a metric.
Theorem 2: Our newly constructed function D has the properties (12), (13), (14) and (15), and therefore can be used as a measure of distances between subsets of S.
Proof: Let 〈S, d〉 be a metric space and let A, B, C ⊂ S be non-empty sets. We have
Property(12) a.k.a. reflexivity: Let us compute D(A, A). Let us choose an arbitrary point a ∈ A. Using Definition 4 (see (20)) we obtain δ(a, A) = 0, because the closest target in A from a is a itself, as it belongs to A. From that it must follow that Δ(A, A) = 0 because the largest of all zeros is zero (peruse (21)). This implies further that D(A, A) = 0 because greater of two zeros is still a zero (see again (22)).
Property(13): Let A ≠ B. Both sets being not empty, we can find an a ∈ A such that a ∉ B, or b ∈ B such that b ∉ A, or both (if this were not the case, then the sets A and B would be equal). Given that at least one of a and b does not belong to both sets, we must have either δ(a, B) > 0 or δ(b, A) > 0 or both. From this we have either Δ(A, B) > 0 or Δ(B, A) > 0 or both, and so D(A, B) > 0 as being greater of the previous two.
Property(14) a.k.a. commutativity follows directly from the Definition 6: D(A, B) = max {Δ(A, B), Δ(B, A)}, so the order of arguments does not matter when evaluating D(A, B).
Property(15) a.k.a. triangle rule: We need to show that D(A, B) ≤ D(A, C) + D(C, B).
A comment on travel from A to B via C: not any path will do. It is not sufficient to reach C from A at particular point c1 ∈ C and then continue the trip from another point c2 ∈ C to reach B to claim that we have traveled through C. Our itinerary must form a continuous path, that is, its first leg must end up at some point c ∈ C exactly where the second leg begins.
Let then the points a ∈ A and b ∈ B be arbitrarily chosen departure and destination points such that d(a, b) = D(A, B). Depending on the metric chosen the path from a to b of length d(a, b) may not be unique. However, each of such paths may or may not pass through our intermediate point c ∈ C. If it does, then we do not modify that path, and so its length does not change. If it does not, then we need to modify it to pass through c. In that situation the length of that path can only increase. Given that D(A, B) is computed using carefully chosen paths leading from a ∈ A to b ∈ B (or vice versa), such modifications of these paths can only result in leaving them intact or lengthening them, thus proving that D(A, B) ≤ D(A, C) + D(C, B). ■
Note that it also follows from this theorem that for our function D the Theorem 1 holds as well.
More importantly for the purposes of our chapter, observe that we may move the sets A and B within their space S so as to minimize D(A, B). Even then, for A and B being different, the residual value D(A, B) > 0 will remain.
With the information regarding the spatial positioning of sets A and B deliberately destroyed through such preprocessing, that residual value D(A, B) can be seen as measure of dissimilarity between sets. The function D can therefore serve also as a pattern classifier. With properly selected small value of ε > 0, the condition D(A, B) ≤ ε implies that A and B so preprocessed are sufficiently similar to be included in the same category.
7. Comparisons of audio patterns
We concern ourselves now with issues of pattern recognition, which in auditory domain call for comparison of audio signals. An audio signal is really a bundle of rectangular pulse signals traveling through fibers of a cochlear nerve. We will take full advantage of their properties arising from the fact that these elementary signals belong to time domain, that is, R1 space.
An audio pattern is an excerpt of an audio signal taken over a suitable time interval. Two audio patterns are similar, if all their elementary corresponding pulse signals are similar, that is, differ at most by an arbitrarily small time value of ε > 0.
7.1 Properties of elementary audio patterns
Our function D, although mathematically correct and theoretically useful in measuring distances and dissimilarities between sets, is only computable for sets belonging to R1 space (time domain). Readers interested in circumventing this limitation are directed elsewhere [2, 3].
Consider now two corresponding elementary signals, shown in Figure 12, as red and blue, for clarity. They are excerpted from two different signal bundles. Clearly, they are not identical. Are they then completely different and unrelated, or is one a subtle plagiarism on the theme of another? Without any numerical measure of their dissimilarity, any two experts may have three different opinions on this matter. We will use our function D as a reconciliation tool.
Figure 12.
Two pulse signals: are they really different? Unrelated? Or is there a similarity?
For the purposes of comparison two signal bundles must be aligned, that is, both must start at the same time, which we will denote as time zero. This means that in each signal bundle there is at least one elementary signal starting at time zero.
However, not all elementary signals in that bundle need to start simultaneously. Indeed, their relative timing is one of the intrinsic characteristics of each signal bundle. We can now define:
Definition 7: The dissimilarity between two signal bundles is the maximum dissimilarity between two corresponding elementary pulse signals in each signal bundle.
We therefore turn our attention to comparisons of elementary pulse signals.
Let us compare first signals consisting of one pulse each. Figure 13 shows all possible relationships between such two signals. We will be calculating the value of Δ(A, B), being the fundamental component of D(A, B). In other words, we will be measuring pseudo-distance from A to B (the pseudo-distance in the inverse direction is measured in identical way). For clarity, in our graphs A will be shown in red, B in blue.
Figure 13.
Possible relationships between two pulse signals.
Furthermore, we adopt the convention that the value tA0 and tA1 are the start and the stop times of pulse A, and the values tB0 and tB1 are accordingly the start and stop times of pulse B.
Translating the formula (21) into plain multi-disciplinary English we write:
Pseudo-distance Δ (A, B) is the distance between the most distant point of A to its closest point in B.
This value describes the worst-case scenario when traveling from A to B in terms of the length of the shortest trip.
We are now in position to compute Δ(A, B) for all variants shown in Figure 13. We have:
These variants can be easily identified and pseudo-distances computed, even by simple systems of several neurons. Observe symmetries in these expressions. On any parallel computer both values | tA0 − tB0 | and | tA1 − tB1 | can be calculated simultaneously, and then the proper value can be used as needed. Needless to say, we treat the brain as a parallel computer.
Do we have all the tools needed to compute distances between elementary pulse signals? Not yet. Not all elementary pulse signals consist of a single pulse each. In certain situations, two pulses in B may be needed to measure Δ(A, B). Figure 14 depicts some of those cases. Signal A consists of one pulse as before, but signal B is now made out of two pulses. To cover these situations, we need to enhance our notation of pulse timing.
Figure 14.
Possible relationships between one-pulse signal A and two-pulse signal B.
An elementary signal X consisting of n pulses we describe now as a tuple of 2n time values < tX0,0, tX0,1, tX1,0, tX1,1, … tXn − 1,0, tXn − 1,1>. We number pulses in signal X starting at 0 and ending at n − 1. In that sense the notations tX4,0 and tX4,1 mean start and stop times of the fifth pulse of signal X (the fifth pulse has a number 4 because computer programmers like it that way!).
Observe now what happens in variant 7 of Figure 14: the point in A most distant from B is that of timing in the middle of the gap between two pulses of B. We have here
ΔAB=tB0,1–tB1,0/2
More importantly, we have arrived at the following result:
Conclusion 1: When measuring pseudo-distances Δ(A, B) the points in A (if any) that are in the middle of gaps in B (if any) must also be considered, as well as the start and end points of A. Still, only the end points in B are of interest.
Therefore, in variant 8 the value Δ(A, B) must be calculated as
ΔAB=maxtA0,0–tB0,0tB0,1–tB1,0/2tA0,1–tB1,1
Consider now the difference between variants 11 and 12. In variant 11 the pulse A extends beyond the middle of the gap between pulses in B, while in variant 12 it does not. Therefore, when calculating Δ(A, B) for variant 11, the value of the expression | tB0,1 − tB1,0 |/2 must be considered, while in variant 12 the existence of the second pulse can be ignored when calculating Δ(A, B) (although it is still relevant for calculation Δ(B, A)). Indeed, should there be more pulses in B following the second pulse of B (variant 12), they all could be ignored when calculating Δ(A, B). Similar situation can arise when a multi-pulse signal B is timed so that the leading pulses of B can be ignored. This is good news, as this situation leads to vastly simplified neural calculations. Simplicity bestows speed; for survival speed is of essence!
Note further that the calculated values of Δ(A, B) depend on whether or not they are arrived at in real time. As an example, consider the situation depicted in variant 13 shown in Figure 14. According to our analysis, the pseudo-distance Δ(A, B) value is Δ(A, B) = |tB0,1 − tB1,0|/2. This is established knowing a priori that signal B consists of two pulses. If, however, we do the comparison between A and B in real time and current time is 12 units, then we are in the situation where the first pulse of B already ended but the second pulse did not begin. We cannot even know whether the second pulse exists. We have no choice but to keep calculating the distance between that part of A which we have experienced already and the only part of the pulse of B we heard so far. This will overestimate the value of Δ(A, B). That value will drop off immediately when we hear the onset of the second pulse of B. In fact, we have established now the following:
Conclusion 2: The calculated values of Δ(A, B) are a function of time. This function is continuous when we have an a priori knowledge of all pulses in A and B (i.e., we compare patterns A and B previously stored in memory), but only piecewise continuous if we calculate Δ(A, B) in real-time (i.e., without such a priori knowledge).
In short: When computing Δ(A, B) in real time, the number of pulses of B to consider is further limited. Only the pulses experienced so far can be considered. This simplification further enhances the speed of calculation thus increasing our chances of survival. The fact that our calculation is less exact is immaterial; our foe suffers from the same handicap.
If we survive the encounter with our foe, when safe we can replay both patterns from memory, refining our calculation and survival strategy. When at leisure we have more time to safely indulge in more complex calculations, refining our forecasting models.
This also explains why we enjoy the same recording of music differently depending on whether we hear it for the first time or not.
A question then arises: Suppose we enjoy a piece of music we hear for the first time. If that pleasure is tied to a certain comparison process, what are we comparing that piece to?
Conclusion 3: When listening to a piece of music (even for the first time) we keep predicting its future passages, on the basis of most recent passages in a certain active time interval. In that sense music must adhere to a certain “grammar” to be found pleasurable.
We are now ready to create a formalism of comparison of two elementary pulse signals.
7.2 Comparisons of elementary audio patterns
Given two multi-pulse elementary patterns A and B, we need to calculate their dissimilarity as a distance D(A, B) = max {Δ(A, B), Δ(B, A)} as per formula (22). Again, we focus our attention at calculating the value Δ(A, B) (The value Δ(B, A) is computed in the same way).
Let A consist of n pulses, while B consists of m pulses. We can represent A and B as follows:
A=∪i=0n−1AiandB=∪j=0m−1BjE23
where Ai and Bj are single pulses.
The value of Δ(A, B) can now be calculated as:
ΔAB=maxΔAiBi=0..nE24
In fact, we can accelerate this computation. We have already observed that when calculating Δ(A, B), not all pulses of B are of interest as possible closest destinations on our travel from Ai to B. We can calculate Δ(A, B) more efficiently as
DAB=maxΔAiB∗i=0..nE25
where B* is a subset of consecutive pulses of B, namely
B∗=∪j=kiliBjE26
where k(i) and l(i) are the first and last pulses of this consecutive sub-sequence of interest when calculating the pseudo-distance from Ai to B.
To give formal justification to this computational short-cut, we need to establish the following:
Theorem 3: Let A and B be two multi-pulse elementary patterns defined as per (23). When calculating the values of Δ(Ai, B), not all pulses of B are relevant. We can limit our attention to a subset of consecutive pulses of B, namely
B∗=∪j=kiliBj
where k, which depends on i is an index of the first pulse of interest, and l, which also depends on i, is an index of the last pulse of interest.
Proof: Consider an arbitrarily chosen single pulse Ai ⊆ A. The starting moment of this pulse, timed at tAi,0 may or may not coincide with a pulse of B. If it does, then that pulse of B is the first pulse of interest. We call it Bk. The pulses preceding Bk (if any) cannot be the target destinations on our journey from Ai to B, because at the moment tAi,0 we are already in B.
If it does not, then the most recent pulse of B preceding the moment tAi,0 is our first pulse of interest. Again, we call it Bk. As before, the pulses preceding Bk (if any) cannot be the target destinations on our journey from Ai to B, because the trip from Ai to Bk is shorter.
In a special case that there is no pulse of B preceding the moment tAi,0 the first pulse of B is Bk.
To identify the last pulse of interest Bl we proceed similarly. The ending moment of pulse Ai, timed at tAi,1 may or may not coincide with a pulse of B.
If it does, then that pulse of B is the last pulse of interest. We call it Bl. The pulses following Bl (if any) cannot be the target destinations on our journey from Ai to B, because at the moment tAi,1 we are already in B.
If it does not, then the most imminent pulse of B following the moment tAi,1 is our last pulse of interest. Again, we call it Bl. As before, the pulses following Bl (if any) cannot be the target destinations on our journey from Ai to B, because the trip from Ai to Bl is shorter.
In a special case that there is no pulse of B following the moment tAi,1 the last pulse of B is Bl. ■
In plain multi-disciplinary English, all this means: it is possible to compare two elementary pulse signals by scanning them simultaneously and chronologically, even in real time. In this situation each signal we need to place in a moving time window, containing relevant pulses only, and keep advancing that window as time goes on.
As said before, every audio signal is a bundle of elementary signals, and therefore comparison of two audio signals also involves usage two advancing time windows. This is not new: we do that intuitively all the time when listening to music. We keep certain passages in a moving time window (i.e., some form of active memory). We consider these passages “current” and give them special attention. We feel pleasure if they continue to remain within a certain anticipated “grammar.” Older passages are kept in another, longer term memory.
We have been listening to and enjoying music since time immemorial. Until now it was just a beautiful emotion. Now we have a mathematical model of that emotion.
8. Final thoughts and recommendations
We are well on our way in gaining insight how our brains work. They are pattern comparison machines. When comparing complex patterns (visual, auditory, gustatory, etc.) complex patterns are decomposed into arrays of simper patterns on which the comparisons can easily be made. These simple comparisons are made in real time and their results are then consolidated into a general conclusion about the complex patterns.
Our analysis of audio signal comparison processes makes us further deduce that:
Two audio signal bundles must consist of the same number of elementary pulse signals to be comparable, and these elementary signals must be compared pairwise;
When an elementary signal in one bundle ceases to exist (due to an accident or a disease), the corresponding pulse signal in another bundle is not fully useful to the brain;
Implanting two incompatible cochlear prostheses in one patient is a grave error in the art, as they generate incompatible thus incomparable bundle signals;
Implanting only one prosthesis is therefore an equally grave blunder, unless it is fully compatible with a healthy cochlea;
Cochlear prostheses should therefore be implanted in pairs and tuned simultaneously to each patient. Such tuning should be an inherent part of the implantation procedure.
In the audio domain two patterns consisting of a different number of elementary patterns cannot be similar—they are intrinsically of a different kind. They cannot be readily compared. Children frequently ask a vexing question: “Daddy, when both of us listen to a piece of music we like, do we feel exactly the same sense of pleasure?” The correct answer is: these feelings are subjective, unknowable to others; they arise in our brains as responses to our individual audio signals. It has been said that each human has approx. 30,000 fibers in the cochlear nerve, but the actual numbers vary among the individuals. Also vary the numbers of cilia, geometries of cochleae, ossicles, etc. No two individuals are alike, and their audio signals are mutually incompatible. So are their emerging feelings of pleasure.
No wonder that the challenges in constructing cochlear prostheses are daunting! No single cochlear prosthesis will fit everybody. It must be customized to an individual.
In the current practice things are done the other way around. Every implant manufacturer swears that his device is “best” but dares to implant it into selected patients only, counting on the plasticity of their brains to adapt to the device. To makes things worse, we tend to implant only one device per person—to avoid “complications.” What complications? In fact, we introduce here unnecessary complications—humans (and other animals) have evolved to have two very similar ears. To ask of the human brain to adapt within a single lifespan to two different and mutually incompatible “ears,” thus generating signals not readily comparable is to ask too much! Practical problems emerge, viz.: how to perform audio location if you have two different hearing organs generating incompatible signals? No wonder that the current implant success rate leaves much to be desired.
Our approach offers new promises, but first and foremost we should customize the cochlear prostheses to our patients, not the other way around. We are well on our way.
The author would like to thank his brother, Dr. W. Gregory Wojcik, MD, for his patient verbal advice and consultations on matters of biology and anatomy.
\n',keywords:"audio pattern recognition, auditory pathway, auditory cilia, cochlea, cochlear model, cochlear nerve signal, cochlear prostheses, mechanoreceptors",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/80191.pdf",chapterXML:"https://mts.intechopen.com/source/xml/80191.xml",downloadPdfUrl:"/chapter/pdf-download/80191",previewPdfUrl:"/chapter/pdf-preview/80191",totalDownloads:40,totalViews:0,totalCrossrefCites:0,dateSubmitted:"November 1st 2021",dateReviewed:"December 4th 2021",datePrePublished:"February 3rd 2022",datePublished:null,dateFinished:"January 23rd 2022",readingETA:"0",abstract:"A model of a fully functional cochlear prosthesis is presented here, simplified by taking into account only those evolutionary features of natural cochleae that contribute to their functionality. The proposed prosthetic device generates a bio-compatible digital signal which can be fed to the cochlear nerve. Subsequently, analysis of cochlear nerve signals is offered, both natural and artificial. To that end a number of mathematical theorems are formulated, proven, and then used to demonstrate that signals obtained from our prosthetic device are useful towards auditory pattern recognition, audio location, and even speech comprehension, as well as understanding and enjoyment of music.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/80191",risUrl:"/chapter/ris/80191",signatures:"Wlodzimierz (“Vlad”) Wojcik",book:{id:"11232",type:"book",title:"Human Auditory System - Function and Disorders",subtitle:null,fullTitle:"Human Auditory System - Function and Disorders",slug:null,publishedDate:null,bookSignature:"Dr. Sadaf Naz",coverURL:"https://cdn.intechopen.com/books/images_new/11232.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80355-190-6",printIsbn:"978-1-80355-189-0",pdfIsbn:"978-1-80355-191-3",isAvailableForWebshopOrdering:!0,editors:[{id:"88753",title:"Dr.",name:"Sadaf",middleName:null,surname:"Naz",slug:"sadaf-naz",fullName:"Sadaf Naz"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. The nature of auditory perception",level:"1"},{id:"sec_3",title:"3. Basic model of auditory perception",level:"1"},{id:"sec_3_2",title:"3.1 Self-test procedures for cochlear prostheses",level:"2"},{id:"sec_4_2",title:"3.2 Audio location using pulse signals",level:"2"},{id:"sec_6",title:"4. The cochlear model and prosthetic device",level:"1"},{id:"sec_7",title:"5. Variation on the theme of metric spaces",level:"1"},{id:"sec_8",title:"6. Computing distances between sets",level:"1"},{id:"sec_9",title:"7. Comparisons of audio patterns",level:"1"},{id:"sec_9_2",title:"7.1 Properties of elementary audio patterns",level:"2"},{id:"sec_10_2",title:"7.2 Comparisons of elementary audio patterns",level:"2"},{id:"sec_12",title:"8. Final thoughts and recommendations",level:"1"},{id:"sec_13",title:"Illustration credits",level:"1"},{id:"sec_14",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'Shannon RV, Zeng FG, Wygonski J, Kamath V, Ekelid M. Acoustic simulations of cochlear implants. Available from: http://www.healthaffairs.uci.edu/hesp/Simulations/simulationsmain.htm [Accessed: September 2010]'},{id:"B2",body:'Wojcik V, Comte P. Algorithms for speedy visual recognition and classification of patterns formed on rectangular imaging sensors. Neurocomputing. 2010;74(1–3):140-154. DOI: 10.1016/j.neucom.2009.10.029'},{id:"B3",body:'Wojcik V, Comte P. Algorithms for speedy visual recognition and classification of patterns formed on rectangular imaging sensors. Technical Report: #CS-08-07. Department of Computer Science, Brock University. Available from: http://www.cosc.brocku.ca/files/downloads/research/cs0807.pdf [Accessed: July 2007]'},{id:"B4",body:'Della Santina CC. Regaining balance with bionic ears. Scientific American [Accessed: April 2010]'},{id:"B5",body:'Crawford J. Living without a balancing mechanism. British Journal of Ophthalmology. 1964;48(7):357-360'},{id:"B6",body:'Minor LB. Gentamicin-induced bilateral vestibular hypofunction. Journal of the American Medical Association. 1998;279(7):541-544'},{id:"B7",body:'Della Santina CC et al. A multichannel semicircular canal neural prosthesis using electrical stimulation to restore 3-D vestibular sensation. IEEE Transactions on Biomedical Engineering. 2007;54(6):1016-1030'},{id:"B8",body:'Standring S et al. Gray’s Anatomy: The Anatomical Basis of Clinical Practice. 40th ed. New York, NY: Elsevier; 2009'},{id:"B9",body:'Shannon-Hartley Theorem. Wikipedia. Available from: http://en.wikipedia.org/wiki/Shannon-Hartley_theorem [Accessed: September 2010]'},{id:"B10",body:'Gokhale AA. Introduction to Telecommunications. 2nd ed. Florence, KY: Thomson Delmar Learning; 2004'},{id:"B11",body:'Gleason AM. Elements of Abstract Analysis. Boston: Jones and Bartlett Publishers; 1991'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Wlodzimierz (“Vlad”) Wojcik",address:"vwojcik@brocku.ca",affiliation:'
Department of Computer Science, Brock University, St. Catharines, Ontario, Canada
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Abdel Rahman",coverURL:"https://cdn.intechopen.com/books/images_new/7747.jpg",editedByType:"Edited by",editors:[{id:"92718",title:"Prof.",name:"Abdel Rahman",middleName:null,surname:"Rehab O.",slug:"abdel-rahman-rehab-o.",fullName:"Abdel Rahman Rehab O."}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9247",title:"Mineralogy",subtitle:"Significance and Applications",isOpenForSubmission:!1,hash:"5149699e666cbb61c220646173769f18",slug:"mineralogy-significance-and-applications",bookSignature:"Ali Ismail Al-Juboury",coverURL:"https://cdn.intechopen.com/books/images_new/9247.jpg",editedByType:"Edited by",editors:[{id:"58570",title:"Prof.",name:"Ali",middleName:"Ismail",surname:"Al-Juboury",slug:"ali-al-juboury",fullName:"Ali Al-Juboury"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7677",title:"Forecasting Volcanic Eruptions",subtitle:null,isOpenForSubmission:!1,hash:"5afd431dd1f4f5081355b017fd17f237",slug:"forecasting-volcanic-eruptions",bookSignature:"Angelo Paone and Sung-Hyo Yun",coverURL:"https://cdn.intechopen.com/books/images_new/7677.jpg",editedByType:"Edited by",editors:[{id:"182871",title:"Prof.",name:"Angelo",middleName:null,surname:"Paone",slug:"angelo-paone",fullName:"Angelo Paone"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8223",title:"Processing and Analysis of Hyperspectral Data",subtitle:null,isOpenForSubmission:!1,hash:"02b920d9c266e28152227280ff18ebbe",slug:"processing-and-analysis-of-hyperspectral-data",bookSignature:"Jie Chen, Yingying Song and Hengchao Li",coverURL:"https://cdn.intechopen.com/books/images_new/8223.jpg",editedByType:"Edited by",editors:[{id:"218017",title:"Dr.",name:"Jie",middleName:null,surname:"Chen",slug:"jie-chen",fullName:"Jie Chen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:69,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"17663",doi:"10.5772/24120",title:"Relationships between Lithospheric Flexure, Thrust Tectonics and Stratigraphic Sequences in Foreland Setting: the Southern Apennines Foreland Basin System, Italy",slug:"relationships-between-lithospheric-flexure-thrust-tectonics-and-stratigraphic-sequences-in-foreland-",totalDownloads:3853,totalCrossrefCites:12,totalDimensionsCites:48,abstract:null,book:{id:"1297",slug:"new-frontiers-in-tectonic-research-at-the-midst-of-plate-convergence",title:"New Frontiers in Tectonic Research",fullTitle:"New Frontiers in Tectonic Research - At the Midst of Plate Convergence"},signatures:"Salvatore Critelli, Francesco Muto,\nVincenzo Tripodi and Francesco Perri",authors:[{id:"55590",title:"Prof.",name:"Salvatore",middleName:null,surname:"Critelli",slug:"salvatore-critelli",fullName:"Salvatore Critelli"},{id:"55592",title:"Prof.",name:"Francesco",middleName:null,surname:"Muto",slug:"francesco-muto",fullName:"Francesco Muto"},{id:"55593",title:"Prof.",name:"Vincenzo",middleName:null,surname:"Tripodi",slug:"vincenzo-tripodi",fullName:"Vincenzo Tripodi"},{id:"85117",title:"Dr.",name:"Francesco",middleName:null,surname:"Perri",slug:"francesco-perri",fullName:"Francesco Perri"}]},{id:"37859",doi:"10.5772/50009",title:"Plate Tectonic Evolution of the Southern Margin of Laurussia in the Paleozoic",slug:"plate-tectonic-evolution-of-the-southern-margin-of-laurussia-in-the-paleozoic",totalDownloads:5295,totalCrossrefCites:15,totalDimensionsCites:45,abstract:null,book:{id:"2227",slug:"tectonics-recent-advances",title:"Tectonics",fullTitle:"Tectonics - Recent Advances"},signatures:"Jan Golonka and Aleksandra Gawęda",authors:[{id:"16567",title:"Dr.",name:"Jan",middleName:null,surname:"Golonka",slug:"jan-golonka",fullName:"Jan Golonka"}]},{id:"57384",doi:"10.5772/intechopen.71049",title:"A Review: Remote Sensing Sensors",slug:"a-review-remote-sensing-sensors",totalDownloads:3674,totalCrossrefCites:24,totalDimensionsCites:42,abstract:"The cost of launching satellites is getting lower and lower due to the reusability of rockets (NASA, 2015) and using single missions to launch multiple satellites (up to 37, Russia, 2014). In addition, low-orbit satellite constellations have been employed in recent years. These trends indicate that satellite remote sensing has a promising future in acquiring high-resolution data with a low cost and in integrating high-resolution satellite imagery with ground-based sensor data for new applications. These facts have motivated us to develop a comprehensive survey of remote sensing sensor development, including the characteristics of sensors with respect to electromagnetic spectrums (EMSs), imaging and non-imaging sensors, potential research areas, current practices, and the future development of remote sensors.",book:{id:"6334",slug:"multi-purposeful-application-of-geospatial-data",title:"Multi-purposeful Application of Geospatial Data",fullTitle:"Multi-purposeful Application of Geospatial Data"},signatures:"Lingli Zhu, Juha Suomalainen, Jingbin Liu, Juha Hyyppä, Harri\nKaartinen and Henrik Haggren",authors:[{id:"213512",title:"Dr.",name:"Lingli",middleName:null,surname:"Zhu",slug:"lingli-zhu",fullName:"Lingli Zhu"},{id:"213522",title:"Dr.",name:"Suomalainen",middleName:null,surname:"Juha",slug:"suomalainen-juha",fullName:"Suomalainen Juha"},{id:"213523",title:"Prof.",name:"Jingbin",middleName:null,surname:"Liu",slug:"jingbin-liu",fullName:"Jingbin Liu"},{id:"220941",title:"Prof.",name:"Juha",middleName:null,surname:"Hyyppä",slug:"juha-hyyppa",fullName:"Juha Hyyppä"},{id:"220942",title:"Prof.",name:"Harri",middleName:null,surname:"Kaartinen",slug:"harri-kaartinen",fullName:"Harri Kaartinen"},{id:"220943",title:"Prof.",name:"Henrik",middleName:null,surname:"Haggren",slug:"henrik-haggren",fullName:"Henrik Haggren"}]},{id:"17670",doi:"10.5772/20299",title:"The Qatar–South Fars Arch Development (Arabian Platform, Persian Gulf): Insights from Seismic Interpretation and Analogue Modelling",slug:"the-qatar-south-fars-arch-development-arabian-platform-persian-gulf-insights-from-seismic-interpreta",totalDownloads:8982,totalCrossrefCites:17,totalDimensionsCites:41,abstract:null,book:{id:"1297",slug:"new-frontiers-in-tectonic-research-at-the-midst-of-plate-convergence",title:"New Frontiers in Tectonic Research",fullTitle:"New Frontiers in Tectonic Research - At the Midst of Plate Convergence"},signatures:"C.R. Perotti, S. Carruba, M. Rinaldi, G. Bertozzi, L. Feltre and M. Rahimi",authors:[{id:"38310",title:"Dr.",name:"Stefano",middleName:null,surname:"Carruba",slug:"stefano-carruba",fullName:"Stefano Carruba"},{id:"42459",title:"Prof.",name:"Cesare",middleName:null,surname:"Perotti",slug:"cesare-perotti",fullName:"Cesare Perotti"},{id:"42460",title:"Dr.",name:"Marco",middleName:null,surname:"Rinaldi",slug:"marco-rinaldi",fullName:"Marco Rinaldi"},{id:"42465",title:"Dr.",name:"Giuseppe",middleName:null,surname:"Bertozzi",slug:"giuseppe-bertozzi",fullName:"Giuseppe Bertozzi"},{id:"42466",title:"Dr.",name:"Luca",middleName:null,surname:"Feltre",slug:"luca-feltre",fullName:"Luca Feltre"},{id:"42467",title:"Dr.",name:"Mashallah",middleName:null,surname:"Rahimi",slug:"mashallah-rahimi",fullName:"Mashallah Rahimi"}]},{id:"9498",doi:"10.5772/8283",title:"Remote Sensing of Forest Health",slug:"remote-sensing-of-forest-health",totalDownloads:5355,totalCrossrefCites:14,totalDimensionsCites:30,abstract:null,book:{id:"3345",slug:"geoscience-and-remote-sensing",title:"Geoscience and Remote Sensing",fullTitle:"Geoscience and Remote Sensing"},signatures:"Jyrki Tuominen, Tarmo Lipping, Viljo Kuosmanen and Reija Haapanen",authors:null}],mostDownloadedChaptersLast30Days:[{id:"71931",title:"Open Pit Mining",slug:"open-pit-mining",totalDownloads:1625,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Open pit mining method is one of the surface mining methods that has a traditional cone-shaped excavation and is usually employed to exploit a near-surface, nonselective and low-grade zones deposits. It often results in high productivity and requires large capital investments, low operating costs, and good safety conditions. The main topics that will be discussed in this chapter will include an introduction into the general features of open pit mining, ore body characteristics and configurations, stripping ratios and stripping overburden methods, mine elements and parameters, open pit operation cycle, pit slope angle, stability of mine slopes, types of highwall failures, mine closure and reclamation, and different variants of surface mining methods including opencast mining, mountainous mining, and artisan mining.",book:{id:"8620",slug:"mining-techniques-past-present-and-future",title:"Mining Techniques",fullTitle:"Mining Techniques - Past, Present and Future"},signatures:"Awwad H. Altiti, Rami O. Alrawashdeh and Hani M. Alnawafleh",authors:[{id:"313182",title:"Prof.",name:"Rami",middleName:null,surname:"Alrawashdeh",slug:"rami-alrawashdeh",fullName:"Rami Alrawashdeh"},{id:"313522",title:"Dr.",name:"Awwad",middleName:null,surname:"Altiti",slug:"awwad-altiti",fullName:"Awwad Altiti"},{id:"313523",title:"Prof.",name:"Hani",middleName:null,surname:"Alnawafleh",slug:"hani-alnawafleh",fullName:"Hani Alnawafleh"}]},{id:"64027",title:"Stages of a Integrated Geothermal Project",slug:"stages-of-a-integrated-geothermal-project",totalDownloads:4341,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"A geothermal project constitutes two big stages: the exploration and the exploitation. Each one has a single task whose results allow defining the feasibility of a geothermal project, until achieving the construction and operation stage of the power generation plant. The first stage contains the area recognition, its limitation to the target, and elimination of external factors until defining a geothermal zone with characteristics to be commercially exploited. The main studies and analysis that can be applied during the exploration stage are listed, and the major indicator to continue with the project or suspend is the prefeasibility report. The major risks in the exploration stage are due to studies that are carried out on the surface; at this stage, the costs can be considered low. The main results of the exploration are the selection of sites to drill three or four initial wells. Each well provides a direct overview of the reservoir: depth, production thicknesses, thermodynamic parameters, and production characteristics. The drilling of three to four exploratory wells is recommended, as far as there is certainty of the feasibility of the project, and the development of the field begins with drilling of sufficient wells to feed the plant. In this stage, the cost increases, but the risks decrease.",book:{id:"7504",slug:"renewable-geothermal-energy-explorations",title:"Renewable Geothermal Energy Explorations",fullTitle:"Renewable Geothermal Energy Explorations"},signatures:"Alfonso Aragón-Aguilar, Georgina Izquierdo-Montalvo,\nDaniel Octavio Aragón-Gaspar and Denise N. Barreto-Rivera",authors:[{id:"258358",title:"Dr.",name:"Alfonso",middleName:null,surname:"Aragón-Aguilar",slug:"alfonso-aragon-aguilar",fullName:"Alfonso Aragón-Aguilar"}]},{id:"63059",title:"Generation, Evolution, and Characterization of Turbulence Coherent Structures",slug:"generation-evolution-and-characterization-of-turbulence-coherent-structures",totalDownloads:3618,totalCrossrefCites:3,totalDimensionsCites:4,abstract:"Turbulence stands as one of the most complicated and attractive physical phenomena. The accumulated knowledge has shown turbulent flow to be composed of islands of vortices and uniform-momentum regions, which are coherent in both time and space. Research has been concentrated on these structures, their generation, evolution, and interaction with the mean flow. Different theories and conceptual models were proposed with the aim of controlling the boundary layer flow and improving numerical simulations. Here, we review the different classes of turbulence coherent structures and the presumable generation mechanisms for each. The conceptual models describing the generation of turbulence coherent structures are generally classified under two categories, namely, the bottom-up mechanisms and the top-down mechanisms. The first assumes turbulence to be generated near the surface by some sort of instabilities, whereas the second assigns an active role to the large outer layer structures, perhaps the turbulent bulges. Both categories of models coexist in the flow with the first dominating turbulence generation at low Reynolds number and the second at high Reynolds number, such as the case in the atmospheric boundary layer.",book:{id:"7214",slug:"turbulence-and-related-phenomena",title:"Turbulence and Related Phenomena",fullTitle:"Turbulence and Related Phenomena"},signatures:"Zambri Harun and Eslam Reda Lotfy",authors:[{id:"243152",title:"Dr.",name:"Zambri",middleName:null,surname:"Harun",slug:"zambri-harun",fullName:"Zambri Harun"},{id:"252195",title:"Dr.",name:"Eslam",middleName:null,surname:"Reda",slug:"eslam-reda",fullName:"Eslam Reda"}]},{id:"64562",title:"Electrical Resistivity Tomography: A Subsurface-Imaging Technique",slug:"electrical-resistivity-tomography-a-subsurface-imaging-technique",totalDownloads:3182,totalCrossrefCites:7,totalDimensionsCites:10,abstract:"Electrical resistivity tomography (ERT) is a popular geophysical subsurface-imaging technique and widely applied to mineral prospecting, hydrological exploration, environmental investigation and civil engineering, as well as archaeological mapping. This chapter offers an overall review of technical aspects of ERT, which includes the fundamental theory of direct-current (DC) resistivity exploration, electrode arrays for data acquisition, numerical modelling methods and tomographic inversion algorithms. The section of fundamental theory shows basic formulae and principle of DC resistivity exploration. The section of electrode arrays summarises the previous study on all traditional-electrode arrays and recommends 4 electrode arrays for data acquisition of surface ERT and 3 electrode arrays for cross-hole ERT. The section of numerical modelling demonstrates an advanced version of finite-element method, called Gaussian quadrature grid approach, which is advantageous to a numerical simulation of ERT for complex geological models. The section of tomographic inversion presents the generalised standard conjugate gradient algorithms for both the l1- and l2-normed inversions. After that, some synthetic and real imaging examples are given to show the near-surface imaging capabilities of ERT.",book:{id:"8361",slug:"applied-geophysics-with-case-studies-on-environmental-exploration-and-engineering-geophysics",title:"Applied Geophysics with Case Studies on Environmental, Exploration and Engineering Geophysics",fullTitle:"Applied Geophysics with Case Studies on Environmental, Exploration and Engineering Geophysics"},signatures:"Bing Zhou",authors:null},{id:"17670",title:"The Qatar–South Fars Arch Development (Arabian Platform, Persian Gulf): Insights from Seismic Interpretation and Analogue Modelling",slug:"the-qatar-south-fars-arch-development-arabian-platform-persian-gulf-insights-from-seismic-interpreta",totalDownloads:8964,totalCrossrefCites:16,totalDimensionsCites:40,abstract:null,book:{id:"1297",slug:"new-frontiers-in-tectonic-research-at-the-midst-of-plate-convergence",title:"New Frontiers in Tectonic Research",fullTitle:"New Frontiers in Tectonic Research - At the Midst of Plate Convergence"},signatures:"C.R. Perotti, S. Carruba, M. Rinaldi, G. Bertozzi, L. Feltre and M. Rahimi",authors:[{id:"38310",title:"Dr.",name:"Stefano",middleName:null,surname:"Carruba",slug:"stefano-carruba",fullName:"Stefano Carruba"},{id:"42459",title:"Prof.",name:"Cesare",middleName:null,surname:"Perotti",slug:"cesare-perotti",fullName:"Cesare Perotti"},{id:"42460",title:"Dr.",name:"Marco",middleName:null,surname:"Rinaldi",slug:"marco-rinaldi",fullName:"Marco Rinaldi"},{id:"42465",title:"Dr.",name:"Giuseppe",middleName:null,surname:"Bertozzi",slug:"giuseppe-bertozzi",fullName:"Giuseppe Bertozzi"},{id:"42466",title:"Dr.",name:"Luca",middleName:null,surname:"Feltre",slug:"luca-feltre",fullName:"Luca Feltre"},{id:"42467",title:"Dr.",name:"Mashallah",middleName:null,surname:"Rahimi",slug:"mashallah-rahimi",fullName:"Mashallah Rahimi"}]}],onlineFirstChaptersFilter:{topicId:"104",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81626",title:"Use of Natural Safiot Clay for the Removal of Chemical Substances from Aqueous Solutions by Adsorption: A Combined Experimental and Theoretical Study",slug:"use-of-natural-safiot-clay-for-the-removal-of-chemical-substances-from-aqueous-solutions-by-adsorpti",totalDownloads:24,totalDimensionsCites:0,doi:"10.5772/intechopen.101605",abstract:"The main objective of this work was to investigate the potential of Natural Safiot Clay (NSC), as an adsorbent for the removal of two cationic dyes such as Basic Blue 9 (BB9) and Basic Yellow 28 (BY28) from single and binary systems in aqueous solutions. For this, the effects of three factors controlling the adsorption process, such as initial dye concentration, adsorbent dose, and initial pH on the adsorption extent, were investigated and examined. The natural safiot clay was characterized using the following technique: energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), DRX, and Fourier transform infrared (FT-IR) and pH of the point of zero charge (pHZPC). Energy-dispersive X-ray spectroscopy results indicate high percentages of Silica and Alumina. FT-IR spectrum identified kaolinite as the major mineral phase in the presence of quartz, calcite, and dolomite. The quantum theoretical study confirms the experimental results, through the study of the global and local reactivity and the electrophilicity power of the dyes. The electrophilicity power of dyes affects the removal efficiency. The theoretical study proves that BB9 (ω = 6.178) is more electrophilic than BY28 (ω = 2.480) and more interactions with surface sites. The results of the molecular dynamics simulation indicate that the dyes are adsorbed parallel to the surface of natural Safi clay (kaolinite), implying the strong interaction with the kaolinite atoms. All the results of quantum chemistry calculations and simulations of molecular dynamics are in perfect agreement with the results of the experimental study.",book:{id:"11137",title:"Mineralogy",coverURL:"https://cdn.intechopen.com/books/images_new/11137.jpg"},signatures:"Aziz El Kassimi, Mohammadine El Haddad, Rachid Laamari, Mamoune El Himri, Youness Achour and Hicham Yazid"},{id:"80866",title:"Normative Mineralogy Especially for Shales, Slates, and Phyllites",slug:"normative-mineralogy-especially-for-shales-slates-and-phyllites",totalDownloads:44,totalDimensionsCites:0,doi:"10.5772/intechopen.102346",abstract:"First, an insight into normative mineralogy and the most important methods for calculating the standard or norm minerals, such as the CIPW norm, is given. This is followed by a more detailed explanation of “slatenorm” and “slatecalculation” for low and very low metamorphic rocks, such as phyllites, slates, and shales. They are particularly suitable for fine-grained rocks where the mineral content is difficult to determine. They enable the determination of a virtual mineral inventory from full chemical analysis, including the values of carbon dioxide (CO2), carbon (C), and sulfur (S). The determined norm or standard minerals include the minerals—feldspars, carbonates, micas, hydro-micas, chlorites, ore minerals, and quartz. The advantages of slatenorm and slatecalculation compared to other methods for calculating normal minerals of sedimentary rocks are discussed.",book:{id:"11137",title:"Mineralogy",coverURL:"https://cdn.intechopen.com/books/images_new/11137.jpg"},signatures:"Hans Wolfgang Wagner"},{id:"80770",title:"Mg-Ilmenite from Kimberlites, Its Origin",slug:"mg-ilmenite-from-kimberlites-its-origin",totalDownloads:57,totalDimensionsCites:0,doi:"10.5772/intechopen.102676",abstract:"The main regularities of the saturation of kimberlite rocks with the accessory mineral Mg-ilmenite (Ilm), the peculiarities of the distribution of Ilm compositions in individual pipes, in different clusters of pipes, in diamondiferous kimberlite fields, are considered as the example of studies carried out within the Yakutian kimberlite province (Siberian Craton). Interpretation of different crystallization trends in MgO-Cr2O3 coordinates (conventionally named “Haggerty’s parabola”, “Steplike”, “Hockey stick”, as well as the peculiarities of heterogeneity of individual zonal and polygranular Ilm macrocrysts made it possible to propose a three-stage model of crystallization Ilm: (1) Mg-Cr poor ilmenite crystallizing from a primitive asthenospheric melt; (2) Continuing crystallization in the lithospheric contaminated melt by MgO and Cr2O3; (3) Ilmenite subsequently underwent sub-solidus recrystallization in the presence of an evolved kimberlite melt under increasing oxygen fugacity (ƒO2) conditions.",book:{id:"11137",title:"Mineralogy",coverURL:"https://cdn.intechopen.com/books/images_new/11137.jpg"},signatures:"Sergey I. Kostrovitsky"},{id:"80553",title:"Investigation of Accessory Minerals from the Blatná Granodiorite Suite, Bohemian Massif, Czech Republic",slug:"investigation-of-accessory-minerals-from-the-blatn-granodiorite-suite-bohemian-massif-czech-republic",totalDownloads:48,totalDimensionsCites:0,doi:"10.5772/intechopen.102628",abstract:"The Central Bohemian magmatic complex belongs to the Central European Variscan belt. The granitic rocks of this plutonic complex are formed by several suites of granites, granodiorites, and tonalites, together with small bodies of gabbros, gabbro diorites, and diorites. The granodiorites of the Blatná suite are high-K, calc-alkaline to shoshonitic, and metaluminous to slightly peraluminous granitic rocks. Compared to the common I-type granites, granodiorites of the Blatná suite are enriched in Mg (1.0–3.4 wt.% MgO), Ba (838–2560 ppm), Sr. (257–506 ppm), and Zr (81–236 ppm). For granodiorites of the Blatná suite is assemblage of apatite, zircon, titanite, and allanite significant. Zircon contains low Hf concentrations (1.1–1.7 wt.% HfO2). The composition of titanite ranges from 83 to 92 mol.% titanite end-member. Allanite is relatively Al-poor and displays Feox. ratio 0.2–0.5.",book:{id:"11137",title:"Mineralogy",coverURL:"https://cdn.intechopen.com/books/images_new/11137.jpg"},signatures:"Miloš René"},{id:"80423",title:"Minerals as Prebiotic Catalysts for Chemical Evolution towards the Origin of Life",slug:"minerals-as-prebiotic-catalysts-for-chemical-evolution-towards-the-origin-of-life",totalDownloads:106,totalDimensionsCites:0,doi:"10.5772/intechopen.102389",abstract:"A transition from geochemistry to biochemistry has been considered as a necessary step towards the emergence of primordial life. Nevertheless, how did this transition occur is still elusive. The chemistry underlying this transition is likely not a single event, but involves many levels of creation and reconstruction, finally reaching the molecular, structural, and functional buildup of complexity. Among them, one apparent question is: how the biochemical catalytic system emerged from the mineral-based geochemical system? Inspired by the metal–ligand structures in metalloenzymes, many researchers have proposed that transition metal sulfide minerals could have served as structural analogs of metalloenzymes for catalyzing prebiotic redox conversions. This assumption has been tested and verified to some extent by several studies, which focused on using Earth-abundant transition metal sulfides as catalysts for multi-electron C and N conversions. The progress in this field will be introduced, with a focus on the CO2 fixation and ammonia synthesis from nitrate/nitrite reduction and N2 reduction. Recently developed methods for screening effective mineral catalysts were also reviewed.",book:{id:"11137",title:"Mineralogy",coverURL:"https://cdn.intechopen.com/books/images_new/11137.jpg"},signatures:"Yamei Li"},{id:"80338",title:"Ionic Conductivity of Strontium Fluoroapatites Co-doped with Lanthanides",slug:"ionic-conductivity-of-strontium-fluoroapatites-co-doped-with-lanthanides",totalDownloads:54,totalDimensionsCites:0,doi:"10.5772/intechopen.102410",abstract:"Britholites derivatives of apatite’s that contain lanthanium and neodymium in the serial compounds Sr8La2−xNdx(PO4)4(SiO4)2F2 with 0 ≤ x ≤ 2 were subject of the present investigation. The solid state reaction was the route of preparing these materials. Several techniques were employed for the analysis and characterization of the synthesized powders. The chemical analysis results indicated that molar ratio Sr+La+NdP+Si was of about 1.67 value of a stoichiometric powder. The X-ray diffraction data showed single-phase apatites crystallizing in hexagonal structure with P63/m space group were successively obtained. Moreover, the substitution of lanthanium by neodymium in strontium phosphosilicated fluorapatite was total. This was confirmed by the a and c lattice parameters contraction when (x) varies coherently to the sizes of the two cations. The infrared spectroscopy and the 31P NMR (MAS) exhibited the characteristic bands of phosphosilicated fluorapatite. The pressureless sintering of the material achieved a maximum of 89% relative density. The sintered specimens indicated that the Nd content as well as the heating temperature affected the ionic conduction of the materials and the maximum was 1.73 × 10−6 S cm−1 obtained at 1052 K for x = 2.",book:{id:"11137",title:"Mineralogy",coverURL:"https://cdn.intechopen.com/books/images_new/11137.jpg"},signatures:"Khouloud Kthiri, Mohammed Mehnaoui, Samira Jebahi, Khaled Boughzala and Mustapha Hidouri"}],onlineFirstChaptersTotal:10},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:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,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:133,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:107,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:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,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:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343",scope:"Biomedical Engineering is one of the fastest-growing interdisciplinary branches of science and industry. The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. 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Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"7",title:"Bioinformatics and Medical Informatics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",isOpenForSubmission:!0,editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",slug:"slawomir-wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",biography:"Professor Sławomir Wilczyński, Head of the Chair of Department of Basic Biomedical Sciences, Faculty of Pharmaceutical Sciences, Medical University of Silesia in Katowice, Poland. His research interests are focused on modern imaging methods used in medicine and pharmacy, including in particular hyperspectral imaging, dynamic thermovision analysis, high-resolution ultrasound, as well as other techniques such as EPR, NMR and hemispheric directional reflectance. Author of over 100 scientific works, patents and industrial designs. Expert of the Polish National Center for Research and Development, Member of the Investment Committee in the Bridge Alfa NCBiR program, expert of the Polish Ministry of Funds and Regional Policy, Polish Medical Research Agency. Editor-in-chief of the journal in the field of aesthetic medicine and dermatology - Aesthetica.",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},{id:"8",title:"Bioinspired Technology and Biomechanics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",isOpenForSubmission:!0,editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",slug:"adriano-andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",biography:"Dr. Adriano de Oliveira Andrade graduated in Electrical Engineering at the Federal University of Goiás (Brazil) in 1997. He received his MSc and PhD in Biomedical Engineering respectively from the Federal University of Uberlândia (UFU, Brazil) in 2000 and from the University of Reading (UK) in 2005. He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). He was the head of the undergraduate program in Biomedical Engineering of the Federal University of Uberlândia (2015 - June/2019) and the head of the Centre for Innovation and Technology Assessment in Health (NIATS/UFU) since 2010. He is the head of the Postgraduate Program in Biomedical Engineering (UFU, July/2019 - to date). He was the secretary of the Parkinson's Disease Association of Uberlândia (2018-2019). Dr. Andrade's primary area of research is focused towards getting information from the neuromuscular system to understand its strategies of organization, adaptation and controlling in the context of motor neuron diseases. His research interests include Biomedical Signal Processing and Modelling, Assistive Technology, Rehabilitation Engineering, Neuroengineering and Parkinson's Disease.",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",isOpenForSubmission:!0,editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",slug:"luis-villarreal-gomez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",biography:"Dr. Luis Villarreal is a research professor from the Facultad de Ciencias de la Ingeniería y Tecnología, Universidad Autónoma de Baja California, Tijuana, Baja California, México. Dr. Villarreal is the editor in chief and founder of the Revista de Ciencias Tecnológicas (RECIT) (https://recit.uabc.mx/) and is a member of several editorial and reviewer boards for numerous international journals. He has published more than thirty international papers and reviewed more than ninety-two manuscripts. 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Banigo, Chigozie A. Nnadiekwe and Emmanuel M. 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For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}}]},{type:"book",id:"7218",title:"OCT",subtitle:"Applications in Ophthalmology",coverURL:"https://cdn.intechopen.com/books/images_new/7218.jpg",slug:"oct-applications-in-ophthalmology",publishedDate:"September 19th 2018",editedByType:"Edited by",bookSignature:"Michele Lanza",hash:"e3a3430cdfd6999caccac933e4613885",volumeInSeries:2,fullTitle:"OCT - Applications in Ophthalmology",editors:[{id:"240088",title:"Prof.",name:"Michele",middleName:null,surname:"Lanza",slug:"michele-lanza",fullName:"Michele Lanza",profilePictureURL:"https://mts.intechopen.com/storage/users/240088/images/system/240088.png",biography:"Michele Lanza is Associate Professor of Ophthalmology at Università della Campania, Luigi Vanvitelli, Napoli, Italy. His fields of interest are anterior segment disease, keratoconus, glaucoma, corneal dystrophies, and cataracts. His research topics include\nintraocular lens power calculation, eye modification induced by refractive surgery, glaucoma progression, and validation of new diagnostic devices in ophthalmology. \nHe has published more than 100 papers in international and Italian scientific journals, more than 60 in journals with impact factors, and chapters in international and Italian books. He has also edited two international books and authored more than 150 communications or posters for the most important international and Italian ophthalmology conferences.",institutionString:'University of Campania "Luigi Vanvitelli"',institution:{name:'University of Campania "Luigi Vanvitelli"',institutionURL:null,country:{name:"Italy"}}}]},{type:"book",id:"7560",title:"Non-Invasive Diagnostic Methods",subtitle:"Image Processing",coverURL:"https://cdn.intechopen.com/books/images_new/7560.jpg",slug:"non-invasive-diagnostic-methods-image-processing",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Mariusz Marzec and Robert Koprowski",hash:"d92fd8cf5a90a47f2b8a310837a5600e",volumeInSeries:3,fullTitle:"Non-Invasive Diagnostic Methods - Image Processing",editors:[{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. 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Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:null},{id:"243698",title:"Dr.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:null,institution:null},{id:"7227",title:"Dr.",name:"Hiroaki",middleName:null,surname:"Matsui",slug:"hiroaki-matsui",fullName:"Hiroaki Matsui",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Tokyo",country:{name:"Japan"}}},{id:"318905",title:"Prof.",name:"Elvis",middleName:"Kwason",surname:"Tiburu",slug:"elvis-tiburu",fullName:"Elvis Tiburu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"336193",title:"Dr.",name:"Abdullah",middleName:null,surname:"Alamoudi",slug:"abdullah-alamoudi",fullName:"Abdullah Alamoudi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"318657",title:"MSc.",name:"Isabell",middleName:null,surname:"Steuding",slug:"isabell-steuding",fullName:"Isabell Steuding",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"318656",title:"BSc.",name:"Peter",middleName:null,surname:"Kußmann",slug:"peter-kussmann",fullName:"Peter Kußmann",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"338222",title:"Mrs.",name:"María José",middleName:null,surname:"Lucía Mudas",slug:"maria-jose-lucia-mudas",fullName:"María José Lucía Mudas",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}}]}},subseries:{item:{id:"2",type:"subseries",title:"Prosthodontics and Implant Dentistry",keywords:"Osseointegration, Hard tissue, Peri-implant soft tissue, Restorative materials, Prosthesis design, Prosthesis, Patient satisfaction, Rehabilitation",scope:"
\r\n\tThe success of dental implant treatment is not solely dependent on the osseointegration around the implant. Aside from the criteria used to describe the hard tissue response at the implant level, the success criteria in implant dentistry include three additional aspects: peri-implant soft tissue, prosthesis, and patient’s satisfaction.
\r\n
\r\n\tThe Prosthodontics and Implant Dentistry topic will provide readers with up-to-date resources on the prosthodontics factors such as aesthetics, restorative materials, the design of prosthesis, case selection, occlusion, oral rehabilitation, among others, all of which play an important role in determining the success of a well osseointegrated implant. With the help of digital dental technology, these can now be accomplished more predictably.
\r\n
\r\n\tThe end goal of prosthesis is always considered when planning successful implant placement. The readers in this field will be able to learn more about taking a holistic approach when treating their dental implant cases.
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