NAFLD activity score (NAS).
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2270",title:"Fourier Transform",subtitle:"Materials Analysis",isOpenForSubmission:!1,hash:"5e094b066da527193e878e160b4772af",slug:"fourier-transform-materials-analysis",bookSignature:"Salih Mohammed Salih",coverURL:"https://cdn.intechopen.com/books/images_new/2270.jpg",editedByType:"Edited by",editors:[{id:"111691",title:"Dr.Ing.",name:"Salih",surname:"Salih",slug:"salih-salih",fullName:"Salih Salih"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"872",title:"Organic Pollutants Ten Years After the Stockholm Convention",subtitle:"Environmental and Analytical Update",isOpenForSubmission:!1,hash:"f01dc7077e1d23f3d8f5454985cafa0a",slug:"organic-pollutants-ten-years-after-the-stockholm-convention-environmental-and-analytical-update",bookSignature:"Tomasz Puzyn and Aleksandra Mostrag-Szlichtyng",coverURL:"https://cdn.intechopen.com/books/images_new/872.jpg",editedByType:"Edited by",editors:[{id:"84887",title:"Dr.",name:"Tomasz",surname:"Puzyn",slug:"tomasz-puzyn",fullName:"Tomasz Puzyn"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"68253",title:"The Rise in the Prevalence of Nonalcoholic Fatty Liver Disease and Hepatocellular Carcinoma",doi:"10.5772/intechopen.85780",slug:"the-rise-in-the-prevalence-of-nonalcoholic-fatty-liver-disease-and-hepatocellular-carcinoma",body:'The liver is a 1.5 kg reddish-brown biochemical processing plant of immense responsibilities that include protein synthesis, xenobiotic or drug metabolism, blood detoxification, and the release of bile acids for digestion. In short, the liver plays a key role in the hemostasis of the body by regulating the levels of sugar, protein, and fat that circulate in the blood. However, obesity, which must be carefully defined according to ethnic-specific BMI cut-off points, may alter normal liver physiology and lead to liver disease [1]. Obesity is at the intersection of the chronic liver disease pathway that includes diabetes, metabolic syndrome (MetS), nonalcoholic fatty liver disease (NAFLD), and hepatocellular carcinoma (HCC). The complex association between obesity and liver function involving NAFLD, HCC, histopathology, and genetic factors is the subject of several collaborative research investigations [2, 3, 4, 5, 6, 7].
Over the past few decades, dramatic changes in lifestyle behaviors and health priorities have contributed to a significant rise in noncommunicable diseases such as obesity and NAFLD. Obesity is highly prevalent in the United States of America, estimated to represent between 30 and 38% of adults with a body mass index (BMI) greater than 30 kg/m2 [8, 9]. Obesity is also a risk factor for metabolic syndrome (MetS), which increases hepatic triglyceride (TGs) depositions. NAFLD is the most common cause of impaired liver function in Western countries, affecting over one quarter of the population [10, 11]. Obesity is driving the rise of NAFLD and nonalcoholic steatohepatitis (NASH), the culmination of the fatty liver disease spectrum that is manifested by ballooning, scarring, cirrhosis, and finally liver failure and HCC [12]. It is estimated that globally the prevalence of NAFLD in the general population is 24–30% [13, 14]. Accounting for errors in accuracy that may exist in indirect measurement methodologies, in the United States, the prevalence of NAFLD in adults has risen from 18% in 1988–1991, to 29% in 1999–2000, to 31% in 2011–2012 [15]. However, the prevalence of NAFLD in the United States diagnosed by ultrasonography alone was estimated to be 24.13% (95% CI 19.73–29.15%) [16].
Nonalcoholic fatty liver disease (NAFLD) is a broad-spectrum disease ranging from fat infiltration of hepatocytes with no symptoms (simple steatosis aka nonalcoholic fatty liver, NAFL) to excess intrahepatic macroglobular and macrovesicular fat accumulation (5–10% by weight of liver) with aggravated inflammation (steatohepatitis aka nonalcoholic steatohepatitis, NASH) in the presence of little ethanol (typically <30 g per day for men and <20 g per day for women) or no alcohol consumption in the last 12 months [12, 17]. It should be noted, however, there is now convincing evidence demonstrating that even “safe” levels of alcohol consumption are associated with adverse health outcomes [17, 18, 19, 20] suggesting that future studies should include only nondrinker individuals in the “NAFLD definition” [21]. Therefore, for NAFLD classification, the patient must show evidence of hepatic fat accumulation in the absence of declared chronic alcohol consumption, or drug use that can induce steatosis, or hereditary disorders. This NAFLD designation excludes both macrovesicular and microvesicular steatosis encompassing certain drugs, toxins, viral hepatitis B (HBV), hepatitis C (HCV) or human immunodeficiency virus (HIV) infections, celiac disease, α-1 antitrypsin deficiency, hepatobiliary infectious diseases, hepatolenticular degeneration, hepatic malignancies, genetic hemochromatosis, Wilson’s disease, lipodystrophy, abetalipoproteinemia, Reye’s syndrome, HELLP syndrome, or decompensated cirrhosis, which may contribute to secondary causes of steatosis and elevated liver enzymes [22, 23, 24]. Additional medications targeted for exclusion are estrogen, sodium valproate, nonsteroidal anti-inflammatory drugs (NSAIDs), calcium antagonists, perhexiline-maleate, and antiretroviral drugs [25, 26, 27]. Appropriate medical history must also be taken to exclude the uncommon causes of fatty liver secondary to treatment with drugs such as amiodarone, diltiazem, steroids, synthetic estrogens, tamoxifen, and highly active antiretroviral therapy; refeeding syndrome and total parenteral nutrition; severe weight loss after jejunoileal or gastric bypass; lipodystrophy; and other rare disorders [28]. There are also strong opinions for the exclusion of “whole-body system diseases” such as inflammatory bowel syndrome, hypothyroidism, and lipoatrophy [25] from the “secondary fatty liver diseases” category because they may also induce liver steatosis.
NAFLD can be distinguished from alcoholic steatohepatitis (ASH) by the absence of alcohol consumption and on histological markers such as sclerosing hyaline necrosis, hepatocyte ballooning, portal granulocytic inflammation, lobular inflammation, satellitosis, perisinusoidal fibrosis, Mallory-Denk bodies, and acute cholestasis among others [29, 30, 31]. However, it is important to note that NAFLD can also coexist with other liver diseases including HCV, hemochromatosis, and alcoholic liver disease, which can accelerate progression to end-stage liver disease (ESLD) [32].
The pathophysiology of NAFLD and its variants is still incompletely understood thereby limiting the availability of effective diagnostic and therapeutic intervention. The ongoing persistence of obesity and the accompanying high rates of diabetes will increase the prevalence of NAFLD [33]. In many cases, the natural cause of the disease is the development of cirrhosis and ESLD as the population ages. Increased mortality rates have been reported in studies that compared NAFLD patients with a normal reference population [34, 35, 36]. The primary cause of death for NAFLD patients is cardiovascular disease followed by nonliver cancer, whereas the third leading cause of mortality is liver-related complications including cirrhosis [33]. The exact prevalence of fatty liver condition is not known, but population studies from the United States and China estimate that 28–30% of the general population has simple steatosis that carries a relatively benign prognosis and is measured using magnetic resonance spectroscopy (the most accurate imaging modality) and that 8% of the population has elevated alanine transaminase (ALT) [37, 38]. A follow-up of population-based studies examining the natural history of NAFLD patients in Minnesota revealed that 3.1% of the patients developed cirrhosis-related complications including ascites (2%), jaundice (2%), encephalopathy (2%), variceal bleeding (1%), and HCC (0.5%) [34]. Approximately 10–30% of those with steatosis develop NASH, and the development of NASH cirrhosis is associated with a poor long-term prognosis for 2.6% of them who will be at a risk of developing HCC [39, 40, 41]. Ten years following diagnosis, 45% will decompensate and the mortality rate for subjects with Child-Pugh A disease will be 20% [42]. Furthermore, besides having an increased liver-related mortality rate compared to the general population, patients with NASH also have an increased risk of cardiovascular death (15.5 vs. 7.5%,
The progression and stages of NAFLD (adapted from Baranova et al., [
The general classification of NAFLD as stated above and accepted by the American Association for the Study of Liver Diseases (AASLD) is a hepatic fat accumulation exceeding 5–10% by weight of the liver [45]. Accordingly, NAFLD diagnosis in the liver is based on: (i) the presence of simple steatosis, as determined by histological or imaging procedure; (ii) a total weekly consumption of less than 140 g of ethanol for men and less than 70 g for women in the last 12 months; and (iii) the absence of competing etiologies for simple liver steatosis and the absence of coexisting causes for chronic liver disease [46]. An appropriate diagnosis of NAFLD, which is multifaceted, requires that there is evidence of hepatic steatosis upon imaging and histology or both and that other causes of liver disease including steatosis have been excluded [23].
The increasing prevalence of obesity in the past few decades has led to a surge in NAFLD, which manifests liver cells as bloated with droplets of fat. It has been reported that 70% of centrally obese patients with diabetes and hypertension (HTN) harbor steatohepatitis on liver biopsy [47]. Imaging has enabled the observation of central obesity in 70–80% of these subjects and in 50–80% of patients with type 2 diabetes mellitus (T2DM). NAFLD is typically asymptomatic; therefore, diagnosis usually follows the subsidiary finding of abnormal liver enzymes or steatosis on imaging. Early diagnosis of NAFLD requires skilled and informed practitioners to halt fibrosis progression to more advanced stages. Liver needle puncture biopsy, although invasive, is the gold standard. Less-invasive methods of image detection tools may not provide consistent information due to the subjective interpretations of the data by radiologists [48]. But imaging tools such as abdominal ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) are beginning to meet this need. Ultrasound or sonography is very effective in diagnosing steatosis where greater than 33% of hepatocytes are steatotic but can be unreliable with lesser degrees of steatosis [49]. The other imaging modalities such as CT or MRI can also detect hepatic steatosis even though they are not used in the evaluation of steatosis. Currently, the combination of MRI and proton magnetic resonance spectroscopy (MRI/1H-MRS) is the most accurate noninvasive measuring tool of steatosis [50, 51]. 1H-MRS, which defines NAFLD as hepatic fat accumulation (steatosis) >5% of total weight of the liver, is the most reliable quantitative tool. However, due to its prohibitive cost, it is not widely available. Ultrasonography, on the other hand, is the instrument of choice for most of the clinics due to its low cost and wide availability even though it is still relatively limited in the detection of inflammation, a more important and higher risk concern than steatosis for fibrosis, cirrhosis, and HCC [52, 53].
Controlled attenuation parameter (CAP), which is a novel ultrasound-based technique that assesses liver stiffness and steatosis simultaneously by employing transient elastography (TE) [54]. This CAP technique has been shown to accurately detect steatosis although its diagnostic threshold has not yet been determined. Obesity and diabetes are the main risk factors for NAFLD [55]. It has been reported that the presence of T2DM significantly increases the prevalence of NAFLD regardless of the diagnostic tool [56]. For example, using controlled attenuation parameter (CAP), the prevalence of NAFLD is estimated at 75% in T2DM population and 40% in the general population, whereas it is 65% and about 37% respectively when measured by 1H-MRS. The prevalence rate goes down when assessed by liver ultrasound, computed tomography, and plasma ALT in that order [56].
In contrast, most global population studies base their NAFLD characterization on less sensitive and less specific surrogate markers of the disease including elevated liver-associated enzymes such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT >40 IU/L in males; >31 IU/L in females) [57, 58]. Furthermore, serum ALT levels are within the range currently considered “normal” in a sizeable proportion of NAFLD subjects [59]. Typically, depending on the reference values from different laboratories, the broad range for normal AST is reported between 10 and 40 IU/L and ALT between 7 and 56 IU/L. This is because ALT usually falls (and AST may rise) as fibrosis progresses to cirrhosis. Mild elevations, which are generally asymptomatic, are considered to be 2–3 times higher than the normal range, and drastic elevations are 5 times higher than the upper limit of normal, which varies according to gender [60]. Moreover, the very selective measurement of ALT level based on race or ethnicity underscores the lack of effective surrogate markers for NAFLD/NASH in the absence of biopsy [61]. Therefore, an innovative approach is needed to use metabolic risk factors to identify subjects with NAFLD/NASH rather than relying on liver enzyme abnormalities.
There is an active research that is underway to discover serum biomarkers for NASH since it is associated with increased apoptosis and therefore blood markers of apoptosis may be instrumental in distinguishing NASH from simple steatosis [62]. Apoptosis activates caspases that cleave various substrates such as cytokeratin-18 (CK-18), a key intermediate filament protein in hepatocytes, that can be detected with an ELISA test using an M30 antibody to identify patients with NASH [63, 64]. However, liver biopsy provides a superior assessment of hepatic steatosis, hepatocellular injury, inflammation, and fibrosis as well as its ability to demonstrate the presence of hepatocyte ballooning and degeneration in association with steatosis as the key histological feature that distinguishes NASH from simple steatosis. Notwithstanding its limitations such as inherent variability in histologic assessment of NAFLD stage and activity, its invasiveness, its high possibility of complications related to liver damage, its proneness to sampling error generated by the operators, and its limitations in accessibility and reproducibility, liver biopsy is still the standard criterion for the most accurate diagnosis of NAFLD and NASH. Also, because only 7–30% of NAFLD patients in the world population had an indication of biopsy for accurate measurement, Younosis et al., re-evaluated and reported the global prevalence of NASH to be between 1.5 and 6.45% and the North American rate at an average of 8.69% (between 7.2 and 14.63%) [4, 65]. Regarding obesity, reports show that NASH can be verified by histological examination in about 47% of all NAFLD cases among obese individuals [66].
Liver fibrosis is the inordinate accretion of extracellular matrix proteins that include collagen in most types of liver disease including NAFLD. Fibrosis stage is a crucial histological variable to predict mortality. There are well-known independent predictors of fibrosis, which is a subway to chronic liver disease state. Some of these risk factors are age (>45–50), BMI (>28–30 kg/m2), insulin resistance (IR), diabetes, and HTN [67]. Staging hepatic fibrosis is essential in all patients with NAFLD to identify individuals with advanced fibrosis (AF) who may later develop liver-related complications such as hepatocellular dysfunction and portal hypertension (PHTN). A noninvasive and an indirect assessment, which is performed in all liver disease patients including children, may include blood tests such as liver function tests (low albumin), complete blood count (thrombocytopenia and neutropenia), and coagulation profile (prolonged prothrombin time) [68]. Among the diagnostic tools used to measure the prevalence of AF in the setting of T2DM versus the general population, vibration-controlled transient elastography shows the highest prevalence rate followed by NAFLD fibrosis score and FibroTest in that order. It should be noted that the prevalence of T2DM significantly increases the prevalence of AF in similar ways to NAFLD [56].
The most widespread clinically implemented histological grading and staging system is the ‘NAFLD activity score’ (NAS) [6] (see Table 1). More recently, the SAF score encompassing an assessment of steatosis (S), activity (A), and fibrosis (F) has been used to produce more accurate measurements of NASH [5]. These recent developments underscore the fact that NAFLD patients can be diagnosed and staged effectively using noninvasive strategies even though liver biopsy can still be applied for individuals with dubious diagnostic tests or if noninvasive staging is unspecified [69]. However, there is no widely available simple blood test or imaging modality that can differentiate simple steatosis from NASH.
Grade | Steatosis (%) | S score | Lobular (L) inflammation | L score | Hepatocyte ballooning (B) | B score |
---|---|---|---|---|---|---|
0 | <5 | 0 | No foci | 0 | None | 0 |
1 | 5–33 | 1 | <2 foci per 200 × field | 1 | Few cells | 1 |
2 | 34–66 | 2 | 2–4 foci per 200 × filed | 2 | Many cells | 2 |
3 | >66 | 3 | >4 foci per 200 × filed | 3 | N/A | N/A |
NAFLD activity score (NAS).
NASH activity grade = total score: S + L + B range (0–8). Score of ≥5 is equivalent to NASH; score of 3 or 4 is borderline NASH; score of ≤2 denotes non-NASH NAFLD. The NAFLD activity score is based on three pathologic features: Steatosis, hepatocyte ballooning degeneration, and lobular inflammation. Higher scoring denotes severity of NASH: >5 = NASH; <5 = No NASH; 3–4 = borderline; none (0); few (1); many (2).
In summary, early diagnosis of NAFLD is essential to halting the progression of the disease. Biopsy is intrusive and therefore cannot be routinely applied. Ultrasound (sonography) and magnetic resonance imaging tools have become alternative noninvasive detection tools that can be routinely employed in clinical practice. The NAFLD activity score is important as part of the diagnosis procedure. But the fibrosis score is just as important. Table 2 shows the fibrosis score currently used to stage the degree of fibrosis in the liver. There are a few noninvasive fibrosis imaging tests on the market such as Fibroscan that offers a liver stiffness measurement (LSM) using pulsed-echo ultrasound as a surrogate marker of fibrosis [70] and acoustic radiation force impulse (ARFI), which uses conventional B-mode ultrasonography to produce an ultrasonic pulse and measure the response of the liver tissue as shear wave velocity [71]. The Centers for Disease Control (CDC) and Prevention projects that diabetes mellitus is likely to impact the fibrosis progression rates, given the close link between diabetes and fibrosis in those with NAFLD [72, 73].
Liver injury | Fibrosis score (0–4)* | Fibrosis stage |
---|---|---|
None | 0 | 0 |
Mild (delicate fibrosis)/zone 3 presinusoidal fibrosis | <5% (0), 5–33% = (1) | 1a |
Moderate (dense fibrosis)/zone 3 presinusoidal fibrosis | >33–66% (2), >66% = (3) | 1b |
Periportal/portal fibrosis | 0 (0), <2 (1), 2–4 (2), > (3) | 1c |
Portal and periportal fibrosis/presinusoidal fibrosis | None (0) | 2 |
Bridging fibrosis | Few (1) | 3 |
Cirrhosis | Many (2) | 4 |
NAFLD fibrosis score (NFS) and stage.
Fibrosis score of F1-F4 is generally considered NASH [4].
Some commercial biomarker tests include enhanced liver fibrosis (ELF), a panel of markers of matrix turnover as tissue inhibitor of matrix metalloproteinase 1 (TIMP1), hyaluronic acid and PIIINP [74] and FibroTest (FT), a panel of markers of fibrosis widely used in France.
Recognizing patients with the metabolic syndrome (MetS) is key to identifying patients at risk of NAFLD. MetS is a group of risk factors that raises risk of heart disease, diabetes, stroke, etc. [75] and is diagnosed when any three of the following five clinical risk factors are present [76]: impaired fasting serum glucose, low levels of serum HDL cholesterol, elevated serum triglycerides (i.e., hypertriglyceridemia), central obesity or larger than cut-off waist circumference (varies according to gender and ethnicity), and high blood pressure (HTN) (see Table 3).
Features | Terms of condition |
---|---|
Blood glucose (sugar) | Fasting, ≥100 mg/dL |
Blood HDL (“good”) cholesterol | ♂ < 40 mg/dL; ♀ < 50 mg/dL |
Blood triglycerides (TGs) | Fasting, ≥150 mg/dL |
Waist circumference | ♂ > 40″; ♀ > 35″ |
Blood pressure (HTN) | ≥130/85 mm Hg |
Features of the metabolic syndrome.*
The MetS is present with any three of the features shown in the table.
♂ = male; ♀ = female; HDL = high-density lipoprotein; ″ = inches.
Insulin resistance is also a major risk factor for the development of steatosis. Once considered benign, NAFL (or simple steatosis), which is defined as the presence of hepatic steatosis with no evidence of hepatocellular injury in the form of ballooning of the hepatocytes, is now believed to be a serious risk factor for progression to liver disease, cardiovascular disease, and mortality [37, 77]. This is because an excess of abdominal fat is most tightly associated with the metabolic risk factors [78, 79]. The duration of obesity and the presence of MetS in an individual patient are closely tied to the risk of developing NASH-related cirrhosis and HCC [80]. Some of the characteristics of MetS are present in most NAFLD individuals, with 65–71% being obese, 57–68% having deranged lipid profiles, 36–70% suffering from HTN, and 12–37% having impaired fasting glucose tolerance [81]. Approximately a third of patients with NAFLD have the full metabolic syndrome and >90% have at least one feature [47]. There is a consensus that considers NAFLD as a hepatic manifestation of the MetS [82, 83]. On the other hand, clinical signs of the disease are manifested in 70–75% of T2DM patients and up to 95% of obese patients [84]. Thus, the development of the MetS, which is an important predictor of NASH in NAFLD patients, poses a sweeping and unfavorable prognosis [85]. IR is a key mediator that links NAFLD and MetS, which is a constellation of anthropometric and metabolic abnormalities (see Table 3 above).
According to the latest data from NHANES (National Health and Nutrition Examination Survey) study conducted between 2011 and 2012, the prevalence of MetS has increased to 35% in American adults [86]. MetS is a risk factor for diabetes and cardiovascular diseases. It induces an abnormal production of hormones such as leptin, adiponectin, and cytokines such as TNF (tumor necrosis factor)-alpha that regulate inflammatory responses and cause disequilibrium between the pro-inflammatory and anti-inflammatory state of the organ [86]. These are mutually antagonistic: the pro-inflammatory factors such as TNF-alpha promote pro-apoptotic processes, recruit white blood cells, and promote insulin resistance. On the other hand, adiponectin acting as an anti-inflammatory factor inhibits fatty acid uptake, stimulates fatty acid oxidation and lipid export, and enhances insulin sensitivity. Both an increase in pro-inflammatory factors and a decrease in anti-inflammatory factors cause a cytokine imbalance that would lead to steatosis (NAFL) followed by necroinflammation (NASH) and IR. There is a supporting evidence that a high TNF to adiponectin ratio promotes fatty liver and steatohepatitis in animal [87] and human [88] studies. The importance of MetS including IR is that it predicts the occurrence of diabetes and cardiovascular diseases, which can further promote the development and progression of arteriosclerosis and HTN leading to significant morbidity and mortality [89]. Also, NAFLD and obesity are risk factors for the progression to fibrosis among HCV-infected patients [90, 91, 92, 93]. Furthermore, elevated levels of ferritin are common in NAFLD patients and typically reflect active IR or underlying inflammatory activity [68, 81, 94]. Therefore, because of many different correlates and etiological factors and an assortment of assessment tools associated with MetS, there are some unresolved uncertainties in the current estimates of the global and the United States prevalence of NAFLD.
Genetic disorders of lipid metabolism can cause hepatic fat deposition. However, they are far less common than excess body weight and features of MetS as risk factors for NAFLD and NASH. Several genes have been associated with NAFLD. These include
A genetic marker,
There is a reported 52% heritability rate of NAFLD, but evidence pertaining to specific genetic mutations is scant according to multivariable models used after adjusting for sex, age, and ethnicity [13]. Although the mechanism is not well understood, genetic mutations in hemochromatosis (HFE) gene, which is responsible for iron uptake and transferrin plasma concentration, may also be associated with NAFLD development [105, 106]. Several other factors have been indicated in the development and outcomes of NAFLD including epigenetic alterations [107, 108], maternal perinatal nutrition [109, 110, 111], and gut microbiota [107, 112, 113, 114]. A recent study also reports a novel pathway in which hepatic vitamin D receptor (VDR) expression is increased in patients with simple steatosis (nonalcoholic fatty liver without inflammation), and the activated VDR upregulates angiopoietin-like protein 8 (ANGPTL8) expression, thus contributing to triglyceride accumulation in human hepatocytes [115]. At any rate, studies have reported that fibrosis-initiated fatty liver disease progresses over many years, thus providing a potential window for intervention by examining disease-progression/modifying factors in NAFLD [116, 117, 118]. It is important to note that increased BMI and insulin resistance have been associated with a more rapid progression to fibrosis [35, 119].
In most epidemiological studies, the prevalence of NAFLD in the general population is determined by imaging or other indirect methods. Accordingly, the epidemiology and demographic characteristics of NAFLD vary worldwide [12, 16]. In epidemiological studies, the pathophysiological aspects, the natural history, and the determinants of NAFLD are important parameters for the diagnosis and evaluation of therapeutic interventions. This section will provide global perspectives on the prevalence of NAFLD (and later HCC) with emphasis on the United States and the possible reasons for the rapid rise.
There are wide-ranging estimates of NAFLD prevalence in the general population of the United States. An estimated 17–51% of adults have NAFLD [23, 120, 121]. Analysis of liver ultrasound data collected between 1988 and 1994 from the NHANES III reported that 19% of adults have NAFLD [122], whereas a meta-analysis of studies from 2006 to 2014 estimated a NAFLD prevalence of 24% (20–29%) in the general population [65]. The prevalence of NASH is difficult to estimate as biopsy is the necessary tool for screening, but it is cost-prohibitive and impractical for a population study.
Globally, NAFLD is a growing cause of chronic liver disease and NASH is replacing HCV infection as the primary reason for LT [13, 123, 124]. The broad category of NAFLD can manifest as NAFL or NASH. Fibrosis precedes cirrhosis and is therefore used as a prognosticator of the clinical risk of progression to cirrhosis and long-term liver-related adverse outcomes and mortality [34]. Recent evidence has shown that NAFLD and NASH can progress to HCC even in the absence of cirrhosis [125, 126, 127]. In most epidemiological studies including the NHANES data set, the assumptions about NASH in the NAFLD population are based on a post-hoc application of liver enzymes (i.e., AST and ALT) and clinical measurements. In the same vein, the fibrosis stages in population-based studies reflect best estimates derived from clinical aids (e.g., fibrosis-4, ALT to platelet ratio index, and NAFLD fibrosis scores) [128, 129]. The current prevalence rates for NAFLD, NASH, and HCC based on definitive clinical manifestations are shown in Table 4.
Status | Definition | Prevalence | Prognosis |
---|---|---|---|
NAFLD | Spectrum of fatty liver disease with <140 g for men and < 70 g for women per week of alcohol consumption | Estimated at 24–30% of global population [13, 14, 16] and at least 31% of US population (7) | — |
NAFL | >5% simple hepatic steatosis by weight of liver without evidence of hepatocellular injury (i.e., hepatocyte ballooning) | >80% of NAFLD patients | Low probability of progression to cirrhosis |
NASH | >5% hepatic steatosis by weight of liver with inflammation and hepatocellular injury with or without fibrosis Confirmed histologically | Estimated at up to 21–59% of patients with NAFLD Estimated at 1.5–6.45% of US general US population [40, 96, 122] | 11% progress to cirrhosis over 15 years |
NASH cirrhosis | Presence of cirrhosis with current or past histologic evidence of steatosis | 10–30% of patients with NASH | About 31% have liver decompensation over 8 years; about 7% develop HCC over 6.5 years |
NASH HCC | Hepatocellular carcinoma induced by NASH | Estimated at annual rate of 2.6–12.8%* | Progresses to end-stage liver disease |
Prevalence of NAFLD and its more progressive forms, NASH and HCC.
The prevalence of NASH-HCC is not firmly established. Data in the table are the annual incidence rate of developing HCC in patients with NASH-related cirrhosis.
Certain risk factors such as advanced age, obesity, ethnicity, and T2DM increase the incidence and prevalence of NAFLD and NASH and have been consistently identified as salient risk factors for fibrotic progression to cirrhosis [130] (see Table 5).
Risk factor | Description | References |
---|---|---|
Age | Risk increases with age | [4, 40] |
Gender | More common in men Higher risk of advanced fibrosis in women | [4, 96, 131, 132] |
Genetics | Patatin-like phospholipase domain-containing 3 gene | [133] |
MetS** | 70–90% of patients have NAFLD MetS is an independent predictor of fibrosis | [85, 95] |
Ethnicity | Elevated risk in Hispanics Lower risk in blacks | [61] |
Diet | Elevated levels of cholesterol and saturated fats High fructose intake, low carbohydrates | [89, 134, 135, 136] |
OSA*** | Increased risk of hepatic fibrosis | [137] |
NAFLD/NASH* risk factors.
NAFLD/NASH = nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.
MetS = metabolic syndrome.
OSA = obstructive sleep apnea.
The current global estimate is that 24–30% of the world’s population is affected by NAFLD [65] and that includes between 80 and 100 million Americans (http://www.mayoclinic.com), making it the primary etiology for liver disease in the United States; see Figure 2.
Global picture of estimated prevalence of NAFLD and distribution of PNPLA3 genotypes adopted from Zobair Younossi [
The increasing incidence of obesity, diabetes, and metabolic syndrome in the United States and Europe may soon catapult NAFLD/NASH to become the most common cause of HCC in developed countries. In the United States, among the more than 26 million people with diabetes, the prevalence of biopsy-proven NAFLD and NASH is as high as 74 and 11%, respectively [138, 139].
The global rise of NAFLD has exasperated the looming healthcare burden of disease. It may be difficult to accurately forecast the current and future burden of a disease that is rapidly progressing. However, there are modeling techniques and approaches that incorporate real-world surveillance data for NAFLD and NASH incidences, which are growing causes of cirrhosis and HCC. As with many models, the utility of the model is linked to the validity of the inputs into the model. One of these modeling approaches is based on the premise that public awareness and government health policies will be able to eventually level off national obesity incidences and prevalence, which in return will level off NAFLD [4]. The interpretation of the output of this and other models attempting to analyze the burden of NAFLD is constrained by the lack of accurate diagnosis of steatohepatitis with simple epidemiologic tools. Nevertheless, the proportion of individuals with NASH in the NAFLD population will probably continue to rise through the next 15 years based on the rising prevalence of diabetes mellitus [4].
Analyzing the cost and burden of disease with respect to NASH has several potential implications. First, it helps introduce strategies and treatment regimen that will stem its exponential rise in incidence and mortality rates; it will reduce the growing contribution of NASH to LT, which is expensive; and due to an oversupply of decompensated cirrhosis, matching organ availability is rare, and insurance companies have exclusive policy of qualifying subjects with NASH-induced cirrhosis based on whether they have associated co-morbidities.
The epidemiology and demographic characteristics of NAFLD vary worldwide. The rise in NAFLD and NASH will balloon the number of patients with decompensated cirrhosis and pose a major emotional and financial burden on subjects and their caregivers, thus adding to the overall cost of health care. Furthermore, the main etiologic factor adding to the burden of HCC is NAFLD [4]. In select NASH-related HCC patients, liver resection and transplantation provide potentially curative therapeutic options; however, these procedures place a significant burden to healthcare resources and utilization [140]. Currently, NASH-related HCC has replaced HCV-related HCC as the fastest growing indication for LT in HCC candidates.
Liver cancer, which has limited therapeutic choices, has the second highest mortality rate in the world [141]. HCC, which can lead to complications such as portal vein thrombosis (PVT), accounts for the majority of primary liver malignancies and is one of the leading causes of death in patients with advanced fibrosis or cirrhosis [141, 142, 143, 144]. HCC can be caused by chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), alcohol abuse, as well as obesity and diabetes-induced MetS. NAFLD often occurs in the setting of metabolic disorders such as obesity and T2DM. These same metabolic conditions are also risk factors for NAFLD-associated HCC, which can materialize in individuals even in the absence of advanced fibrosis or cirrhosis. NASH-HCC appears to be phenotypically different from HCC arising from other chronic liver diseases (Table 6). By all accounts, the formation and progression of HCC are multistep processes. Therefore, the specific and detailed molecular events that underlie HCC development remain only partially understood [143].
Hepatitis B infection (HBV) |
Hepatitis C infection (HCV) |
Hepatitis D infection (HDV) |
Alcohol (ethanol) |
Nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) |
Obesity/diabetes |
Hereditary hemochromatosis |
Aflatoxin B |
Tyrosinemia |
Glycogen storage disease type 1a |
Oral contraceptives |
Smoking |
Cirrhosis* |
Common risk factors for hepatocellular carcinoma.
Diagnosis of cirrhosis is based on the presence of the ICD-9 codes for cirrhosis or complications of cirrhosis (gastroesophageal varices, encephalopathy, and nonmalignant ascites) recorded at least twice in any inpatient or outpatient encounter.
Primary liver cancer in 2012 was identified as the second most common cause of cancer-related death in the world. In the United States, HCC is the most common histological subtype of liver cancer that accounts for 70–85% of primary liver malignancies [145, 146]. It is also the most rapidly rising cause of cancer and cancer-related deaths with an incidence that has more than tripled over the last two decades. This high mortality reflects a poor prognosis and a poorer therapeutic intervention [147]. Compared to HCC caused by alcoholic liver disease and viral hepatitis, there is a lack of strong epidemiological data associated with the incidence and prevalence of HCC precipitating from NAFLD [140, 148]. While the prevalence of NAFLD is thought to be highest among Hispanics and Caucasians, the ethnic distribution among NAFLD-/NASH-related HCC patients has yet to be defined. Male patients are overrepresented in NASH-related HCC; however, gender has not been proven to be a statistical risk factor in NASH progression to HCC [7]. The rising incidence of NAFLD/NASH in the setting of obesity has led to a drastic growth in NASH-related HCC incidence [149]. Although NAFLD can present with HCC in the absence of NASH or cirrhosis, the cumulative annual incidence rate for developing HCC in patients with NASH-related cirrhosis is approximately 2.4–12.8% [125]. This suggests or utmost underlies that cirrhosis may be the main cause of HCC despite new emerging data suggesting that NAFLD may be an independent risk factor for HCC, even in the absence of cirrhosis [126, 150, 151].
There was also a twofold increase in the incidence of HCC in the United States over the past two decades, and it is projected to double over the next two decades. Compared to HCC in alcoholic liver disease and viral hepatitis, there is a lack of strong epidemiological data regarding the incidence and prevalence of HCC in NAFLD [148]. It is projected that in just 12 more years, HCC at its current pace of growth in the United States will outstrip breast and colorectal cancers as the third leading cause of cancer-related death. This is because the prevalence of HCC is expected to increase by 149% from 10,000 to 24,900 during 2015–2030, while the incidence of HCC cases is expected to increase from 5160 to 12,240 in 2030, an increase of 137% [4]. This alarming incidence is attributed to several different genetic and epigenetic alterations that are under investigation [4].
Modeling the epidemic of HCC suggests that in 2015, 3280 incident HCC cases were estimated to have progressed from compensated cirrhosis (64% of total), with the remaining 1880 incident cases occurring among ≤F3 (fibrosis score-3) cases [4]. By 2030, 8790 incident HCC cases are predicted to occur among compensated cirrhotic cases or 72% of the annual incidence, reflecting aging and disease progression [4].
The true prevalence of NASH and NASH-related HCC is probably underestimated. This is because in 6.9–29% of HCC cases, the underlying etiology is unknown, further questioning the designation that the liver disease is secondary to cryptogenic cirrhosis [148]. Traits of NASH are more frequently observed in HCC patients with cryptogenic cirrhosis than in age- and sex-matched HCC patients of well-defined viral or alcoholic etiology [152]. In the past several years, myriad studies have tried to determine the variability of relationships between NAFLD/NASH, cryptogenic cirrhosis, and HCC. In a recent meta-analysis, White et al. [125] estimated that 60% of HCC cases ascribed to NAFLD/NASH had cirrhosis either prior to diagnosis or at the time of diagnosis. This same analysis showed that NASH-associated cirrhosis consistently manifested an increased HCC risk. Furthermore, the study also revealed that when compared to those with chronic HCV, the risk of developing HCC is lower in patients with cirrhosis due to NAFLD/NASH (HCV, 19.7% vs. NAFLD/NASH, 26.9%) [125]. Although the prevalence of NAFLD-/NASH-related HCC is not well delineated, the growing incidence of obesity and diabetes suggests the impact of NAFLD-/NASH-related HCC will continue to grow.
Genomic analyses promise to improve tumor characterization for the optimization of precision or personalized medicine for patients with HCC. Recent developments and molecular techniques have significantly improved our understanding of the pathogenesis of HCC and its complex genetic landscape [153, 154, 155, 156]. The integration of several profiling data from various sources may provide additional insight into the molecular mechanisms of HCC [153]. The first large-scale multiplatform analysis of HCC conducted as part of The Cancer Genome Atlas (TCGA) network included valuation of somatic mutations by whole exome sequencing and DNA copy number analyses in 363 patients whose tissue and tumor specimens were obtained [157]. This high-throughput analysis also included further investigation of DNA methylation, mRNA expression, microRNA (miRNA) expression, and proteomic expression in 196 patients. To decipher the molecular landscape of HCC and extract biological insights for therapeutic targets and prognostic implications, analyses were made by integrating multiple data platforms with the available clinical data for HCC [157]. Mutational and DNA sequencing analyses identified an array of genes altered either by downregulation or by mutation. Among the significantly mutated genes were EEF1A1, SMARCA4, LZTR1, and SF3B1 [157]. Those genes downregulated by hypermethylation including ALB, APOB, and CPS1 may cause metabolic reprogramming in HCC. The analysis of integrated molecular platform also yielded the identification of a subtype linked to poorer prognosis in three HCC cohorts. This large-scale multiplatform, high-throughput analysis enabled the design of a p53 target gene expression signature correlating with poor survival. This TCGA network analysis produced potential therapeutic targets including WNT signaling, IDH1, MET, VEGFA, MCL1, MDM4, TERT, and immune checkpoint proteins PD-1, PD-L1, and CTLA-4 [157]. This is significant because effective inhibitors already exit for these targets, which alter hepatocyte energy balance [157].
In exome sequencing analysis of over 200 liver tumors, investigators identified mutational signatures that are associated with specific risk factors such as alcohol and tobacco consumption and exposure to aflatoxin B1 [158]. As a result, they found that 161 putative driver genes were associated with 11 recurrently altered pathways involving
The most reported signaling pathways in HCC. Adapted from Birgani et al. [
In another recent study, gene expression and DNA methylation profiles were screened to identify potential genetic biomarkers of HCC. The findings from this study suggest potential HCC biomarker roles for certain genes such as
Validation of liver-enriched genes and KEGG analysis. (A) an example of liver-enriched genes. SPP2 was exclusively expressed in the corresponding nontumor tissues of HCC. (B) Four-set Venn diagram showing the overlap of the liver-enriched genes derived from the TCGA and three other databases, including HPA, PaGenBase, and TiGER. (C) Significantly enriched KEGG pathways of 188 liver-enriched genes. −log10 (adjusted p-value) was annotated on each bar of the KEGG pathway. Adapted from Binghua et al. [
Circulating regulatory nucleic acids like miRNA profiles can also reflect the pathogenic changes occurring in organs including the liver. Changes in miR-21, miR-122, and miR-223 were correlated with the histological status of the human liver and were specific for liver injury [163]. These miRNA levels were significantly higher in the serum of chronic hepatitis (i.e., HBV and HCV) and HCC patients compared to healthy controls [44]. Yet, the biological heterogeneity of HCC makes it difficult to clarify the key mechanisms of cancer initiation and progression, and thereby develop and implement effective therapies [164].
A recent Markov model was used to predict incidence of NAFLD and to forecast NAFLD disease progression in the United States. The model was based on historical and projected changes in adult prevalence of obesity and T2DM as well as national surveillance data for incidence of NAFLD-related HCC [4]. The report forecasts that prevalent NAFLD cases will increase to 21% (100.9 million) by 2030, while prevalent NASH cases will increase 63% from 16.5 million to 27.00 million cases [4]. Overall NAFLD prevalence among the adult population (aged ≥15 years) is projected at 33.5% in 2030, and the median age of the NAFLD population will increase from 50 (estimated at 2015 level) to 55 years between 2015 and 2030 [4]. In 2015, approximately 20% of NAFLD cases were classified as NASH and are expected to increase to 27% by 2030, a reflection of both disease progression and an aging population. The estimated prevalence of NASH in adults living in the United States is 3–5% [6, 23, 121, 165] and is projected to increase by 63% from 16.5 million in 2015 to 27.00 million cases in 2030 [4]. This prevalence of NASH was calculated based on published estimates and modeling of fibrosis progression. It was assumed that up to 5% of NAFLD cases without NASH could be NASH regressors, with most NASH regressors still in F0 stage [4]. Similarly, the incidence of decompensated cirrhosis will surge by 168% to 105,430 cases in 2030, while incidence of HCC will increase by 137% to 12,240 cases. Liver deaths are estimated to increase 178% to 78,300 deaths in 2030. During 2015–2030, there are projected to be nearly 800,000 excess liver deaths. The aging population, the continuing high rates of adult obesity, and T2DM will propel NAFLD-related liver disease and mortality in the United States. Immediate strategies are required to curtail new NAFLD cases and mitigate disease burden.
Currently, NAFLD is estimated to affect more than 80 million and up to 90 million Americans, making it the most common etiology for liver disease in the United States [16, 65]. In the United Kingdom, NAFLD has now become the most common cause of abnormal liver function tests (LFTs) [166]. Although NAFLD has emerged as a serious disease in affluent Western economies, its global prevalence encompasses the Middle East (32%), South America (31%), Asia (27%), the United States (24%), Europe (23%), and Africa (14%) [167]. Because of the increasing incidence of obesity and diabetes around the world, NAFLD has become a global public health concern. The prevalence of NAFLD varies according to age, sex, and the methodology used to measure the condition in each geographical location [61]. Currently, NAFLD is the most prevalent liver disease observed in patients with obesity, diabetes, and metabolic syndrome (MetS), all of which can confer insulin resistance (IR) and are known risk factors for the development of HCC, a growing indicator of LT [45, 69]. While HCV infection has been the most common indication for liver transplants to date, NASH is surpassing it as obesity reaches historic highs and new direct-acting antiviral (DAA) drugs are essentially curing hepatitis C [168]. Furthermore, with the continued decline in the prevalence of HCV infection, the proportion of NASH-HCC is anticipated to increase exponentially due to the growing epidemic of obesity and diabetes [140]. Currently, NASH-related HCC is the fastest growing indication for LT in HCC candidates [140]. NAFLD and NASH are a growing cause of cirrhosis and HCC.
Globally, Asia is leading the rise in NAFLD followed by the United States. Although our understanding of NAFLD is steadily evolving, it is not an isolated disease. It is commonly associated with the leading metabolic comorbidities such as obesity, MetS, T2DM, and dyslipidemia. The potential progression of NAFLD subtypes is from fibrosis to advanced fibrosis, ESLD, and HCC (Figure 1). As the incidence of obesity and concurrently diabetes and MetS continues to surge in Europe and the United States, NAFLD/NASH may become the most common cause of HCC in developed countries in the foreseeable future [169, 170, 171].
A 2002–2012 retrospective cohort study among adult patients revealed a fourfold increase in patients undergoing LT for NASH-related HCC in contrast to only twofold increase in number of patients undergoing transplantation for HCV-related HCC. In the United States, about 6000–7000 liver transplants are performed annually, and the rapid increase in the percentage (44.9%) of obese individuals during a 14-year period (2000–2014) is expected to escalate to 55% the number of NASH patients awaiting LT by 2030 [172]. The increased morbidity and mortality, healthcare costs, and declining health-related quality of life associated with NAFLD require more in-depth analysis. Figure 5 depicts the proposed mechanisms that ties NAFLD/NASH and HCC.
Risk factors and proposed mechanisms for NAFLD- and NASH-related HCC, which is multifactorial. Proposed pathogenic mechanisms include obesity, peripheral and hepatic IR from T2DM, increased hepatic lipid storage and lipotoxicity, genetic mutations, and intestinal microbiota dysregulation. HCC, hepatocellular carcinoma; EMT, epithelial to mesenchymal transition; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; FFA, free fatty acid; IGF, insulin-like growth factor; LPS, lipopolysaccharide;
Although still not fully resolved, the prevalence of NAFLD in the United States can vary by ethnicity. Even in this context, there are several factors that could explain the reported ethnic disparities. These include access to health care, genetic factors, environmental factors, affliction with chronic diseases, and the presence of chronic diseases such as the MetS [61, 65, 173]. In this context, the prevalence of NAFLD is reported to be highest in Hispanic-Americans, followed by Americans of European descent and then African-Americans [40, 61, 65, 122, 173]. Several studies have shown a relative sparsity of NAFLD cases among individuals of African descent living in or coming from Africa or the Caribbean region. Although the prevalence of metabolic disease and obesity is high in Afro-Caribbean ethnic groups compared to Caucasian and Hispanic groups, the frequency of NAFLD/NASH is reported to be low [61, 174]. This discrepancy might be due to an actual low number rate or biases that include low-recognition and low-referral rates in these ethnic minorities [175], as Afro-Caribbean patients are categorically less likely to be referred to other tertiary hospitals [176].
There are also ethnic differences in the incidence of HCC in the United States (see Sherif et al. for a comprehensive review) [61]. Compared to European-Americans (EAs), the incidence of HCC is higher in African-Americans (AAs) and is associated with more advanced tumor stage at diagnosis and lower survival rates overall. Assessment of changes in the levels of metabolites of samples stratified by race was made using gas chromatography-mass spectrometry in selected ion monitoring mode to identify ethnically diverse biomarkers in HCC between EA and AAs [177]. Race-specific metabolites including alpha tocopherol for AA and EA combined, glycine for EA, and valine for AA exhibited better sensitivity and specificity than the standard serological marker for HCC, alpha-fetoprotein (AFP) that is widely used for the diagnosis of HCC [177, 178, 179, 180]. It is hypothesized that there is a variation in HCC-associated epigenetic modifications between AAs and EAs. Thus, the identification of aberrant DNA methylation and differentially modulated miRNAs can be used to better understand the mechanisms of disparities in HCC between races. Also, identifying epigenetic markers for HCC in a specific population will enhance personalized medicine that targets specific therapeutic approaches [181, 182]. This also demands the gathering together of a highly interdisciplinary team of experts to investigate changes in both DNA methylation and miRNA expression patterns between tumor, cirrhotic, and normal liver tissues from AA and EA participants. Identifying molecular cancer gene drivers and mutations may 1 day become critical for precision oncology.
Most epidemiological studies document prevalence of individual diseases in selected tertiary hospital populations [183]. This widespread practice, particularly when imaging and liver enzyme tests are involved and when the patients may be asymptomatic in the early stage of diagnosis, leads to underestimation and underdiagnosis of NAFLD. This is especially true for minority populations in whom the natural development and progression of NAFLD and NASH are understudied and underreported as reflected by the paucity of data in the literature. Furthermore, the predictive value of the MetS may not reflect the true state of NAFLD in AAs since the criteria for the syndrome were developed for non-Hispanic whites [184] thereby influencing underdiagnosis or misdiagnosis of NAFLD and NASH in Hispanics and non-Hispanic blacks (NHB). There is also a strong relationship between insulin resistance and hypertriglyceridemia, one of the crucial components of MetS. However, NHB often have normal triglycerides (TG) level [185], which is used as a diagnostic criterion of the MetS leading to underdiagnosis of the MetS in NHB [186]. This suggests that lowering the threshold for TG level in AAs will lead to grasping the true cases of NAFLD. Moreover, the racial differences in NAFLD and NASH may be a function of the differences in TGs or the differences in the distribution of adiposity (e.g., subcutaneous vs. visceral) since AAs have relatively less VAT and lower TGs than Hispanics [119, 173, 175]. In addition, AAs may be more resistant to both the accretion of TG in the abdominal visceral compartment (adipose tissue and liver) and hypertriglyceridemia associated with IR [119].
Epidemiologic studies establish the foundational framework for the control and prevention of diseases. In the case of NAFLD and NASH, it should be done by first tracking the prevalence of the disease, characterizing its natural history, and identifying both its social and health determinants along ethnic lines. This type of study is critical for the proper diagnosis and early intervention of NAFLD especially in minority populations [61].
Genome-wide association studies have revealed several genetic variants that are associated with NAFLD and NASH. Yet, these variants either represent only a limited amount of variation in hepatic steatosis among ethnic groups or may just be markers representing a larger body of genetic variations.
There is an urgent need to gain a better understanding of the underlying biological mechanisms responsible for why some people with NAFLD are more prone to developing HCC, and the causes for disparities in NAFLD-related HCC. There is also an urgent need for a less invasive method than biopsy and for a more sensitive biomarker than ALT for large-scale NAFLD screening. The lack of high-throughput studies employing proteomics or metabolomics for the discovery of novel and reliable diagnostic biomarkers for NAFLD also hampers our understanding of the pathophysiology of the disease among the disparate ethnicities [12, 177].
One recent area of exploration is the involvement of DNA methylation and miRNA regulation. Epigenetic alterations are potentially reversible, and this possibility will facilitate the development of biomarkers and therapeutics in the prevailing disparities between AA and EA patients in HCC initiation and development. The identification and functional validation of race-specific methylation hotspots and miRNAs can be used to understand the mechanisms of disparities in HCC. This can be done by first identifying DNA methylation sites and miRNAs with statistically significant changes between HCC cases and cirrhotic or normal controls in a race-specific manner. Then, network-based methods and hierarchical integrative models can be used to integrate epigenomic data with transcriptomic, proteomic, glycoproteomic, and metabolomic data acquired from the same cirrhotic and HCC participants to select methylation hotspots and miRNAs relevant for understanding the mechanisms of disparities in HCC [177]. The selected candidates can then be validated by independent methods using frozen and formalin-fixed, paraffin-embedded (FFPE) liver tissues collected from patients with HCC and liver cirrhosis. Finally, functional validation of race-specific epigenetic modifications discovered in this type of high-throughput study can be performed through
In addition to exploring the external environment and how it influences HCC disease status, it is also necessary to explore the intestinal environment of different ethnicities. Experimental data from the obesity epidemic have revealed that the composition and products of the gut microbiome, which is altered with obesity and/or a high fat diet, are carcinogenic to the liver [187, 188]. Studies suggest that there are ethnic differences in microbial composition in a cirrhotic population at elevated risk for HCC as a result of metabolites, which can differentiate cirrhotic with HCC from those without HCC. Therefore, a case-control study can be designed to examine the contributions of race/ethnicity, fecal microbiome, fecal metabolome, and host factors (e.g., specific dietary factors and markers of body and liver fat composition) to NAFLD-related HCC. All in all, a multiethnic study of NAFLD and HCC that encompasses all racial/ethnic groups is needed to lay the groundwork for the elucidation of factors that account for health disparities across these populations. The prevalence of NAFLD is reported to be highest among Hispanics and Caucasians as mentioned above. However, NASH was the leading cause of waitlist LT registration in 2016 among Asian, Hispanic, and non-Hispanic white females, whereas HCV is still the leading cause in AA females [189].
As for gender differences in NAFLD or NASH, there are uncertainties including the role of IR in the influence of gender on NAFLD. Ruhl et al. reported that NAFLD is about 2.7 times more prevalent in men than in women [190]. One reasonable explanation for this reported gender difference in NAFLD is due to the higher waist-to-hip circumference (WHR) ratio in men [96]. Pan et al. further state that WHR is associated with visceral adipose tissue (VAT), which is correlated with both peripheral and hepatic IR. Similarly, in the Dallas Heart Study, European-American (EA) men had an approximately twofold higher prevalence of hepatic steatosis than EA women. This gender disparity has been blamed on alcohol use, sex hormones or lifestyle behaviors, and no differences in body weight or insulin sensitivity [96].
The ethnic distribution among NAFLD-/NASH-related HCC patients has yet to be defined [191]. If the increase in the number of ethnic groups waitlisted for LT from 2004 to 2016 is a good indicator of the rise in NASH-HCC, then it could be inferred from a recent retrospective study that Asian females had an 854% change in NASH waitlist registration, while Asian males had a 552% change [189]. The increase in African-American waitlist population was much less compared to the other ethnic groups. In contrast, the Hispanic females had a 3010% change in the rate of waitlist registration for NASH with HCC, while non-Hispanic white females had a 1992% change [189].
NASH-related HCC patients are primarily male even though gender is not a proven statistical risk factor in the progression of NASH to HCC. However, NASH is currently the second leading cause for LT waitlist in females, whereas in men, alcoholic liver disease (ALD) continues to be the leading cause [189]. Although old data of 698 patients from biopsy-proven NASH show that NASH patients are more likely to be female than male possibly reflecting a higher disease burden rate in women [192], it is likely that both gender and racial ethnic differences in NAFLD and NASH are attributed to interaction among genetic, environmental, and lifestyle behaviors.
The biological heterogeneities of NAFLD and HCC create predicaments in deciphering the key mechanisms of development and progression from NAFLD to ESLD. Although progress is being made in understanding the molecular underpinnings of chronic liver disease and its various offshoots, there are still formidable challenges in providing effective treatment regimens. Aside from a few prophylactic agents that have shown promise in the prevention and treatment of steatohepatitis and fibrosis, there is no treatment consensus due to scarcity of data [140]. Wholesome lifestyle and behavioral changes that include regular physical activity, low caloric intake, and weight loss are the main bulwarks against NAFLD, which may progress to HCC with or without cirrhosis. However, the extent to which these modifications are effective to prevent the development of HCC is unclear. There is currently no effective chemoprevention to decrease the incidence of HCC except using nucleoside analogs to reduce viral replication for those infected with HBV [193] and direct-acting antivirals (DAAs) for those infected with HCV [194], the latter demonstrating very high cure rates but also raising concerns about the recurrence or development of HCC after the achievement of a sustained virological response [195]. Obeticholic acid (OCA), a selective agonist of the Farnesoid X receptors, was touted to be a promising pharmacological drug for the management of NAFLD. However, its low efficacy and specificity have dampened enthusiasm for its practical use. Also, the drug pioglitazone has no long-term impact on NASH. This entails a pressing need to develop more effective and safe agents for NAFLD and HCC. Several other experimental studies suggest a direct role for vitamin D in modulating liver fibrosis and inflammation by enhancing hepatic response to insulin via binding to vitamin D receptor on liver cells [196, 197, 198]. Vitamin E and carotenoids are also shown to decrease plasma levels of patients with NASH [199], whereas dietary antioxidants such as vitamin C and coenzyme Q12, trace minerals such as selenium, anticholesterol medications such as statins, antidiabetic drugs such as metformin, and methyl radical donors such as S-adenosylmethionine have all been touted as potential prophylactic agents [169, 200, 201, 202].
Hepatic steatosis is associated with many other morbidities. Therefore, dissecting the myriad causative agents including genetic, hormonal, or environmental factors underlying the pathogenicity of simple hepatic steatosis must be a priority to avoid the maze of complications that may arise during the development of NAFLD and its progression to HCC. The key findings are:
Global prevalence of NAFLD is at 24% but is rising to greater than 30%; highest rates to lowest rates are found in South America, Middle East, Asia, United States, and Europe.
The large volume of patients sets NAFLD apart from other liver diseases; thus, clinical care must focus on discerning highest risk of progressive liver disease.
Overweight in childhood and adolescence is associated with the risk of NAFLD later in life and increases liver-related morbidity and/or mortality.
NAFLD patients have an elevated risk of liver-related morbidity/mortality and metabolic comorbidities, which place a strain on healthcare systems.
NAFLD warrants that primary-care physicians, specialists, and health policy-makers stress prevention of excessive weight gain during childhood.
Bariatric surgery may be an alternative option to committed weight loss.
Older age, being male, and HA are independent risk factors for NAFLD/NASH.
NAFLD is linked with higher BMI, higher HTN, and lower physical activity.
MetS as currently defined is not a good predictor of NAFLD in non-Hispanic blacks (NHB); because in contrast to others, TG level is normal in this group.
Proton magnetic resonance spectroscopy is currently the best proven alternative tool to biopsy for accurate diagnosis of NAFLD.
Treatment options require more robust studies on etiology of NAFLD.
There is no proven medical therapy for NASH.
Most effective therapeutic strategies include lifestyle changes including diet, exercise, modifying metabolic risk factors, early screening, and intervention.
Certain genes may be associated with disparities in lipid metabolism.
Alternative noninvasive markers of NASH may now be available even though there are no proven biomarkers for various stages of the NAFLD spectrum.
Discovery of new biomolecules during clinical trials and metabolomics studies is crucial for understanding NAFLD/NASH initiation and progression.
Patients with NASH have a worse prognosis and must be included in clinical trials of new treatments.
The biological heterogeneity of HCC makes it difficult to assess the key mechanisms of cancer development and thus implement effective therapies.
Certain genes have been identified to be associated with progression to HCC.
This work was supported by the National Institutes of Health (NIH) Grant U01CA185188.
The author has no conflict of interest.
AA | African-American |
AF | advanced fibrosis |
ALT | alanine aminotransferase |
AST | aspartate aminotransferase |
BMI | body mass index |
CDC | Centers for Disease Control and Prevention |
DAA | direct-acting antiviral |
EA | European-American |
ESLD | end-stage liver disease |
HA | Hispanic-American |
HCC | hepatocellular carcinoma |
HDL | high-density lipoprotein |
HTN | hypertension |
IR | insulin resistance |
LT | liver transplantation |
MetS | metabolic syndrome |
NAFL | nonalcoholic fatty liver |
NAFLD | nonalcoholic fatty liver disease |
NASH | nonalcoholic steatohepatitis |
NFS | NAFLD fibrosis score |
NAS | NAFLD activity score |
NHANES | National Health and Nutrition Examination Survey |
NFS | NAFLD fibrosis score |
T2DM | type 2 diabetes mellitus |
TG | triglyceride |
TCGA | the cancer genome atlas |
Bentonite clay is a volcanic rock that was deposited as volcanic ash in fresh or salt water millions of years ago. It was first discovered in 1890 in Wyoming (Montana, USA) near the Fort Benton site, hence its name. Currently there are a large number of bentonite deposits in the world, in USA, in Europe, in North Africa, in Japan, in China … In Algeria, the most economically important bentonite deposits are found in the west. We note in particular the quarry of Maghnia (Tlemcen) with reserves estimated at one million tons and that of M’zila (Mostaganem) with reserves of two million tons [1, 2].
Bentonite is very soft plastic clay composed mainly of montmorillonite, a clay mineral 2: 1 type of phyllosilicate family formed of fine particles. Montmorilonite consists of two tetrahedral layers (SiO4) separated by an octahedral layer (Al(OH)6), its chemical formula is (Al, M2+)2 Si4 O10 (OH)2, n H2O with M2+ = Mg, Fe, … (Figure 1) [3]. The total thickness of the sheet is approximately 14 Å. Montmorillonites has a negative charge on the surface, neutralized by compensating cations, the main origin of this surface charge comes from isomorphic substitutions resulting from the replacement of the metal cations of the lattice by cations of the same size but of lower charge (the substitution Al3 + by Mg2 + or Fe2+ and the substitution of Si4 + by Al3 +).
Montmorillonite structure.
Bentonite has a privileged place in the purification of water [4, 5]. High specific surface area, chemical and mechanical stabilities, layered structure, high cation exchange capacity (CEC), tendency to hold water in the interlayer sites, and the presence of Brønsted and Lewis acidity have made clays excellent adsorbent materials [6, 7]. The chemical nature and pore structure of bentonite generally determine their adsorption ability [8, 9].
The adsorption properties of natural clay minerals can often be improved either by intercalation of organic, inorganic, or organometallic molecules in the interlamellar space, or by heat or acid treatments [10, 11]. XRD measurements show that intercalation increases the spacing between layers. Among these modifications, the insertion of clays by poly cationic solutions has been used widely in recent years [12, 13]. In addition to their catalytic power, they are presented as excellent adsorbents. The main qualities that these pillared clays can develop are a high specific surface area and a large pore volume.
For the poly cation intercalation pillars to execute correctly, the synthesis protocol must pass through three steps: the first is to prepare the pillaring solution based on multivalent cation such as Al3+, Fe3+ or Cr3+. The second is the impregnation of the polycationic solution within the interlayer space [10, 14]. The last step is the calcination at temperature between 400 and 500 °C in order to solidify the pillars [15]. Some examples for montmorillonite intercalating by polycations cited in literature are the following: china montmorillonite was pillared by solution of Al13 polycations to eliminate cadmium [16], the bentonite of Turkish origin pillared with Fe and Cr was applied as adsorbent for carbon oxide (CO2) and hydrogen H2 [17], the Al/Ti and Al/Zr- pillared montmorillonites from Brazilian Amazon was used for zinc cation removal [18] and Fe/Zr-pîllared montmorilointe (Guangdong, China) was tested for Cr(VI) removal [19].
The organic intercalation of montmorillonite can significantly enhance the organophilicity of the resultant product. Cationic organic compounds, such as surfactant cations, exchange the interlayer cations of montmorillonite [20], and the resulting organoclay is excellent for diverse organic pollutants, e.g. phenol [21], dye [22], and VOCs [23, 24]. Quaternary alkylammonium compounds (bromides or chlorides) are the most commonly employed for intercalation into bentonites. Due to their long-chain they offered to the clays a larger interlayer spacing. The most quaternary ammonium surfactants used are cethyltrimethyl ammonium bromide (CTMAB), tetramethyl ammonium (TMA), trimethyl-phenyl ammonium (TMPA), dodecyl trimethyl ammonium and dimethyl sulfoxide (DMSO).
Unfortunately, sometimes the insertion of a surfactant weakens the specific surface of an organo-clay. To remedy this disadvantage, it’s preferable to combine the intercalation of organic pillar with another mineral. For example, Jiang et al. used hexadecyltrimethyl ammonium bromide added to Al/Fe-pillared montmorillonite [25]. Zhu’s group prepared an intercalated montmorillonite with both hexadecyltrimethyl ammonium bromide and Al13 cations, and discussed the influence of the addition sequence of these two modifiers on the final products [26].
Another method applied to improve adsorption capacity of bentonite consists of the reaction of clay minerals with a strong mineral acid solution, usually hydrochloric acid (HCl) or sulfuric acid (H2SO4). Acid activation leads to modification of Mt. with improved properties such as enhanced surface area, pore diameters, number of acid sites, and catalytic activities. The treatment of the naturally occurring and purified Mt. with hot mineral acid replaces exchangeable cations with H+ ions. Gradual leaching of Al3+ out of both tetrahedral and octahedral sites occurs, but the silicate groups remain largely intact [27, 28].
Dyes released into wastewaters of different industrial plants such as dye manufacturing, textile, paper and food, are toxic, not degradable and stable. The presence of these substances in the surface waters can be carcinogenic and causes damage to human beings, such as dysfunction of kidneys and central nervous system [29, 30].
Pesticides are synthesized substances or biological agents used for attracting any pest. They are mainly applied in agriculture to protect crops from insects, weeds, and bacterial or fungal diseases during growth [31]. Some pesticides, like fungicides are used to kill or inhibit growth of fungi or insects that parasitize crops [32]. Pesticides originating from human activity can also enter water bodies through surface runoff, leaching, and/or erosion. Pesticides can cause endocrine disruptions and neurological disturbancies, influence immune system, reproduction and development [33].
Wastewaters containing dyes or pesticides are often treated by conventional methods as ozonation, membrane filtration, reverse osmosis, oxidation, ion exchange coagulation and adsorption [34, 35, 36, 37, 38]. Adsorption is considered as an attractive and favorable alternate for the removal of dyes and other organic molecules from wastewater streams. Many efforts have been made to find an appropriate adsorbent. Clay adsorbents enable to adsorb anionic and cationic pollutants such as dyes, pesticides and metal ions.
In this context, the present chapter focused in the application of Mostaganem bentonite in the treatment of natural water contaminated by dyes and pesticide. We will also study the phenomenon of adsorption of these pollutants through the use of mathematical models to determine the reaction mechanism, kinetics and thermodynamics of adsorption.
Bentonite used in this investigation was purchased from M’zila deposit (Mostaganem, Algeria). This material is commercialized as industrial charge bentonite without additives by ENOF Company. The physicochemical properties of bentonite are resumed in chemical composition, point of zero charge, cation exchange capacity (CEC) and different analyses techniques such as XRD, FTIR, SEM and Specific surface area (BET).
The aim of the present study was the adsorption of two dyes, acid yellow E-4G and reactive yellow MX-4R. For this purpose two adsorbents were used: (i) bentonite intercalated by hydroxy-aluminum cations, (ii) bentonite pillared by cethyltrimethyl ammonium cation.
Bemacid Yellow E 4G (C.I. acid Yellow 49) and reactive Procion Yellow MX 4R (C.I. Reactive Yellow 14) were supplied by SOITEX textile society (Tlemcen, Algeria). The chemical formula and molecular weight of E-4G and MX-4R are C16H13Cl2N5O3S; 426.24 g/mol and C20H19ClN4Na2O11S3; 669.02 g/mol, respectively. A stock solution (1.0 g/L) of dye was prepared by dissolving accurate weight amount in deionized water and the other concentrations were obtained by dilution of this stock dye solution.
The product chlorothalonil (Chl) fungicide was removed by acid activated bentonite from aqueous solution. Chl was obtained by Syngenta Protection of Plants S.A, Bale, Switzerland. It contains 400 g/L of chlorothalonil in the form of concentrated suspension with some impurities. The Chl is an inhibitor of spore germination, which acts on various enzymes and on the metabolism of fungi. The chemical formula of Chl is C8Cl4N2, and its molecular weight is 265.93 g/mol. The solubility of chlorothalonil in water is 0.6 mg/L at 20 °C.
The Al(III)-modified bentonite was obtained by mixing AlCl3 solution (0.2 mol/L) with sodium hydroxide solution (0.2 mol/L) at 60 °C, up to the molar ratio OH−/Al3+ = 2 [39]. The solution was aged at room temperature for three days before using. The resulting pillaring solution was added to the bentonite by stirring for 4 h at 70 °C at the ratio of 50 mmol oligomeric cations per gram of bentonite [40]. The slurry was stirred for 24 h at room temperature, filtered, and washed repeatedly with deionized water. The solid was dried at 80 °C and kept in a sealed bottle. The pillared bentonite obtained was designated as B-Al.
The surfactant CTAB intercalated bentonite was synthesized as follows: the amount of CTAB (175 mg) corresponding to 1.0 times CEC of bentonite was dissolved in 1 L of distilled water at ambient temperature and stirred for 24 h. A total of 1 g bentonite was added to 100 mL surfactant solution. The dispersion was stirred for 4 h at 60 °C. The separated sample was washed several times and dried at 80 °C. The final product was noted as B-CTAB.
Raw bentonite was treated by hydrochloric acid (HCl) (37% purity, Merck) at different concentrations (0.1, 1 and 6 N) at 70 °C. The amounts of 4 g of each treated sample were added to 400 mL of acid solution [41]. The contact time of the samples with the acid solution was fixed as 4 hours. At the end of treatment, the bentonite was washed several times with distilled water and dried over night at 80 °C [42].
The adsorption experiments were carried out in a series of Erlenmeyer flasks containing 0.1 g of B-Al or B-CTAB and 20 mL of dyes aqueous solution at the desired concentration and initial pH (adjusted with hydrochloric acid 0.1 N or 0.1 N NaOH) in ambient temperature bath (23 °C). After shaking for 3 h of contact time, the flasks were removed and the concentration of MX-4R and E-4G after the adsorption was analyzed by spectrophotometer at wavelength of 425 and 400 nm, respectively. The adsorbed amount of dye (mg/g) was calculated as follow:
where,
The chlorothalonil was prepared in the range of initial concentrations 100–500 mg/L, in order to know the maximum amount of fungicide that bentonite can adsorb. For each experiment, 20 mL of pesticide solution was added to 0.1 g of the solid. The suspension was shaken at room temperature (23 °C) for 3 h. The chlorothalonil was detected by spectrophotometer at wavelength of 360 nm.
The chemical analysis of raw bentonite was performed by X-fluorescence XRF 9900. Thermo Instrument. The result of this analysis revealed that the silica (64.22%), alumina (11.62%) and lime (9.33%) are the main oxides of the bentonite with the existence of the others oxides in the small amounts such as Fe2O3 (4.88%), TiO2 (1.06%), Na2O (3.38%) and P2O5 (0.03%). The elementary analysis of M’zila bentonite gives the formula Na0.13, Ca0.01, K0.10, (Al1.24 Mg0.2 Fe0.17 Ti0.01) (Si4.24) O10 (OH)2 with mass molar 368.68 g/mol [43].
The pHPZC value purified bentonite was found as 6.8. This value informs us about the electric charge on the solid surface. At pH value below than pHPZC the electrical charge on the surface is positive, it will be negative at pH higher than pHPZC. Cation exchange capacity of natural bentonite was determined to be 112 meg/100 g by applying the conductimetric titration method [44]. The BET specific surface area measured via Quantachrome instrument was found 59.02 m2/g.
The diffractogram of raw bentonite was shown in Figure 2. The bentonite sample contains some mineral phases such as the Montmonrillonite (M), Kaolinite (K), Calcite (C), Quartz (Q) and Dolomite (D). The characteristic peak d001 of montmorillonite appears at 2θ = 5.5°, the kaolinite is observed at 2θ = 10° and the peak of calcite appears at 2θ = 31°.
XRD pattern of raw bentonite.
The FT-IR spectrum of raw bentonite was performed with Agilent Cary 630 Spectrometer in range of 4000–400 cm−1. The FT-IR analysis illustrated in Figure 3 shows an intensive band at 1000 cm−1 which is attributed to the Si-O in plan stretching vibration and other bands at 520 and 470 cm−1 assigned to Al- O- Si (octahedral Al) and Si- O-Si bending vibrations, respectively [45]. The small band at 1620 cm−1 is attributed to the deformation vibrations of the O–H bond of the constitution water. The band at 3620 cm−1 is assigned to hydroxyl groups Al3+ is partially replaced by Fe3+ and Mg2+.
FT-IR spectra of raw bentonite.
The images of scanning electron microscope were made by microscope JSM-6360 to observe the morphology of bentonite particles. According to the Figure 4 the particles were formed by heterogeneous aggregates of different shape and size. It appears that these grains constitute a stack of sheets probably representing the clay layers. On the surface of the sample, a small luminous crystallite settles, may be of free silica (quartz).
SEM images of natural bentonite extension 3000 and 9000.
According to the XRD analysis realized with INEL CPS 120 instrument employing cobalt radiation (λ = 0.178 nm), the hydroxy-aluminum polycations exchange increases the
XRD patterns of natural and pillared bentonitew.
The addition of surfactant causes the increasing of basal spacing of the bentonite around 18 Å, indicating location of CTA+ ions between layers of montmorillonite. In order to increase more again the basal spacing, it must be increase in CTA+ concentration, because as known, the amount of added surfactant has a direct effect on the interlayer expansion of Mt.
The pillaring bentonite with hydroxy-aluminum and CATB generated an enhancement of specific surface area where the values found were 110 and 194.4 m2/g for B-Al and B-CTAB, respectively. These values were very higher than that of untreated bentonite (59.02 m2/g). In the case of Al-modified bentonite the specific surface area was increased significantly but a slight increase was noted through the basal spacing. This is due to the existence of electrostatic bonding between the negatively charges layers and pillaring oligocations in uncalcined Al-pillared clay.
The second application deals with the acid activation of Algerian bentonite and testing of his capacity to remove the chlorothalonil fungicide in aqueous solution. The hydrochloric acid solutions were used in the concentration range of 0.1-6 N.
The specific surface area of bentonite treated by 1 N (BA1N) and 6 N (BA 6 N) of hydrochloric acid were determined as 82.22 and 80.55 m2/g, respectively. We see that the specific surface areas of both activated bentonites are almost identical, which are much higher than that of the raw bentonite (59.02 m2/g). The specific surface area greatly increases at the acid concentration of 1 N, but slightly decreases at the concentrations higher than this value and then does not change much. Similar results were found by activating bentonite with sulfuric acid [47, 48].
The XRD patterns of raw and activated bentonites at various concentrations (0.1, 1 and 6 N) were shown in Figure 6. We note that there is no difference between the spectra of BN and BA 0.1 N. The concentration of 0.1 N of hydrochloric solution seems not be sufficient to make significant changes in the structure of bentonite. This means that it is a cation exchange causing the substitution of the exchangeable cations of interlayer space by protons H+. In contrast to the sample treated with 0.1 N, the samples BA 1 N and BA 6 N undergo a significant structural modification according to the XRD spectra, where we notice that the peaks of montmorillonite and the kaolinite almost disappeared, while that of the illite is reduced in intensity. So from 1 N concentration of HCl, the clay minerals of bentonite are exposed to the direct effect of acid leading to the destruction of the basic clay sheets.
XRD patterns of raw and activated bentonites.
This process generally increases the surface area and the acidity of the clay minerals [49].
The adsorption isotherms are realized at different initial concentrations of dyes, adsorbent dose was 5 g/L, and pH effect was tested and maximum adsorbed amount of dye was noted at pH = 2–3. The isotherms are formed by amount of dye adsorbed by the plot vs. equilibrium concentration. The adsorption isotherms of MX-4R and E-4G by the pillared bentonites are presented in Figure 7. The results show that the amount of dye adsorbed increases with the increase in equilibrium concentration of dye. All isotherms are of S-shape according to the classification of Giles et al. [50]. This type of isotherm originates from the cooperative isothermal adsorption, i.e. the adsorbed molecules promote higher adsorption of other molecules and tend to be adsorbed in groups. The maximum adsorbed amounts registered were 93.91 and 92.75 mg/g for MX-4R and E-4G respectively, attributed to B-CTAB sample. Those of B-Al adsorbent were 66.08 and 87.72 mg/g, respectively. According to these results, the B-CTAB sample has adsorption capacity most important than that of B-Al for the both dyes, in same operating conditions.
Adsorption isotherms of (a) MX-4R and (b) E-4G onto B-Al and B-CTAB. (C0 = 200–500 mg/L, pH = 2–3, adsorbent dose 5 g/L, contact time 3 h)
The adsorption isotherms were fitted by Langmuir and Freundlich equations expressed in linear forms in relations (2) and (3), respectively:
where
The Langmuir and Freundlich constants and the linear regression correlations (R2) for both isotherms model are listed in Table 1. The results reveal that the adsorption isotherms correlate with Freundlich model because the correlation coefficient (R2) values obtained were above 0.98, while the model of Langmuir describes less well the experimental data where the linearization constants were insignificant except in the case of MX-4R. However Freundlich model is well used to describe the adsorption behavior of dyes on the both materials. This can be explained by the fact that the Langmuir equation is valid for monolayer adsorption onto a surface containing a finite number of identical sites, while Freundlich isotherm represents satisfactorily the sorption data on heterogeneous surfaces.
Model | Langmuir | Freundlich | |||||
---|---|---|---|---|---|---|---|
Constants | Q0(mg/g) | KL (L/mg) | R2 | 1/n | KF mg/g(L/mg)1/n | R2 | |
B-Al | E-4G | ins | ins | ins | 1.396 | 2.96 | 0.984 |
MX-4R | 76.92 | 0.044 | 0.989 | 0.455 | 8.60 | 0.988 | |
B-CTAB | E-4G | ins | ins | ins | 0.920 | 3.177 | 0.955 |
MX-4R | 113.63 | 0.137 | 0.994 | 0.346 | 28.73 | 0.984 |
Linearization constants of Langmuir and Freundlich equations.
ins: insignificant results.
To evaluate the adsorption rate, the adsorption kinetic was examined by pseudo-first order and pseudo-second order models. The evolution of adsorption capacity of MX-4R and E-4G dyes increases over time and attained an equilibrium state around 60 min. The adsorption rates of the E-4G and MX-4R by intercalated bentonites are rapid early in the process and becoming slower over time. The pseudo-first order kinetic using the linear Lagergren equation is generally expressed as follows [51]:
where
The pseudo-second order kinetic is expressed as follows [52]:
where
The calculated qe values agree with the experimental qe values, and the correlation coefficients for the pseudo-second-order kinetic plots were also found to be very high (R2 = 0.98), indicating that pseudo-second order model fitted very well the kinetic adsorption. The pseudo second order model is based on the assumption that the rate limiting step may be chemisorption which involves valence forces by sharing or electron exchange between the adsorbent and the adsorbate [53]. According to the Table 2, the rate constants increase from 0.002 and 0.011 g.mg−1 min−1 (B-CTAB) to 0.922 and 0.912 g.mg−1 min−1 (B-Al). This means that the adsorption of dyes onto B-Al is a fast reaction, and CTAB-modified bentonite has a best adsorption capacity due to its high porosity and its large specific surface area.
B-Al | B-CTAB | |||
---|---|---|---|---|
Model | E-4G | MX-4R | E-4G | MX-4R |
Pseudo-first order | ||||
qe(cal)(mg/g) | 0.835 | 19.36 | 35.70 | 3.010 |
K1 (min−1) | 0.019 | 0.065 | 0.043 | 0.019 |
R2 | 0.809 | 0.902 | 0.970 | 0.350 |
Pseudo-second order | ||||
qe(cal)(mg/g) | 12.048 | 45.455 | 42.016 | 60.24 |
K2 (g/mg.min) | 0.922 | 0.912 | 0.002 | 0.011 |
R2 | 0.999 | 0.997 | 0.996 | 0.999 |
qe(exp)(mg/g) | 11.865 | 44.207 | 38.926 | 59.588 |
Constants rates of the E-4G and MX-4R adsorption by B-Al and B-CTAB.
The Figure 8 shows the adsorption of Chl by the activated bentonite. This figure indicates that the adsorbed amount of Chl onto raw and activated bentonite increases in parallel with the equilibrium concentration. The experimental isotherm obtained here may be classified as type S referring to the classification of Giles et al. This type of isotherm originates from the cooperative isothermal adsorption, i.e. the adsorbed molecules promote higher adsorption of other molecules and tend to be adsorbed in groups. We note also that the activated bentonite adsorbs much better than the natural bentonite. When the activated samples were compared, it was found that the maximum amount of adsorption (38.42 mg/g) was observed for BA 1 N.
Adsorption isotherms of Chl onto activated bentonite.
The isotherm model fit the experimental data very well is Freundlich model. The Freundlich equation is an empirical equation that can be used for heterogeneous systems with interaction between the molecules adsorbed. As seen from Table 3, the values of regression coefficients R2 were close to the unit and the 1/n values were less than unity which indicates that the adsorption intensity was favorable and was a physical process. On the other hand, the experimental data fitted by Langmuir model were insignificant in terms of adsorption; this is why they are not mentioned.
Sample | T (K) | KF (mg/g (L/mg)1/n) | 1/n | R2 |
---|---|---|---|---|
BA 0.1 N | 296 | 0.913 | 0.737 | 0.935 |
BA 1 N | 296 | 0.590 | 0.939 | 0.925 |
303 | 2.064 | 0.725 | 0.950 | |
313 | 2.295 | 0.831 | 0.979 | |
323 | 2.087 | 0.736 | 0.970 |
The constants of Freundlich model.
In the case of adsorption of molecules on a solid surface, the Gibbs energy is composed of two functions, the enthalpy function (
The distribution coefficient Kd (L/g) is calculated from the following Equations [54, 55]:
where
It can be seen from Table 4 that the calculated
C0(mg/L) | ∆H° (kJ/mol) | ∆S° (J/molK) | ∆G° (kJ/mol) | ||||
---|---|---|---|---|---|---|---|
303 K | 313 K | 323 K | R2 | ||||
BA 1 N | 30 | 68.894 | 234.292 | - 2.096 | - 4.439 | - 6.782 | 0.930 |
40 | 34.020 | 120.528 | - 2.499 | - 3.705 | - 4.910 | 0.895 | |
50 | 29.726 | 107.381 | - 2.810 | - 3.883 | - 4.957 | 0.927 | |
60 | 39.861 | 137.879 | - 1.915 | - 3.294 | - 4.673 | 0.926 | |
80 | 40.422 | 141.319 | - 2.397 | - 3.810 | - 5.223 | 0.910 |
Heats adsorption of Chl onto activated bentonite.
In this research we studied the characteristics and the physicochemical properties of an Algerian bentonite which its adsorption capacity was tested to eliminate organic pollutants from aqueous solution.
Before the adsorption experiment, bentonite underwent two different treatments in order to improve its exchange capacity and porosity. The first treatment carried out is that of the pillaring clay with mineral (polycations of Al13) and organic (CTAMB) intercalants. The second is the treatment by acid attack (HCl) at different concentrations (0.1, 1 and 6 N).
The intercalation of the bentonite by Al13 and CTAB increased the basal sheet space up to 14.3 and 18 Å, respectively. The chemical activation with HCl at 6 N concentration enhanced the specific surface area of the bentonite from 59.02 to a value of 82 m2/g. The obtained materials from the both treatments were applied for the adsorption of MX-4R, E-4G dyes and the fungicide chlorothalonil.
The adsorption isotherms of these pollutants have shown that the adsorption capacities were very satisfactory and the adsorption phenomenon was physical nature. The adsorption isotherms of all adsorbates were well described by Freundlich model. Kinetic data of dyes adsorption tend to fit well in pseudo-second order rate expression. Moreover the adsorption of chlorothalonil by activated bentonite was spontaneous and this spontaneity increases with increasing temperature.
The authors declare no conflict of interest in publishing this chapter.
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As the science gets more advanced and the information about these two points becomes clearer, the view of this information might modify our understanding to these processes. Then, some topics might be dropped, and others might be raised or become more obvious. However, the feeding of halophyte forages as per se has several drawbacks and therefore, they have to be fed in mixed rations, fortifying these rations with energy supplements.",book:{id:"5978",slug:"new-perspectives-in-forage-crops",title:"New Perspectives in Forage Crops",fullTitle:"New Perspectives in Forage Crops"},signatures:"Salah A. Attia-Ismail",authors:[{id:"204190",title:"Emeritus Prof.",name:"Salah",middleName:"Abdelaty",surname:"Attia-Ismail",slug:"salah-attia-ismail",fullName:"Salah Attia-Ismail"}]},{id:"56029",doi:"10.5772/intechopen.69614",title:"Production of Spineless Cactus in Brazilian Semiarid",slug:"production-of-spineless-cactus-in-brazilian-semiarid",totalDownloads:1875,totalCrossrefCites:4,totalDimensionsCites:8,abstract:"The term “spineless cactus” is used in Brazil to designate cultivars of Opuntia ficus indica Mill and Nopalea cochenillifera Salm Dyck. The spineless cactus was consolidated in Brazilian semiarid as a strategic fundamental food resource in several production livestock systems, constituting a plant with enormous productive potential. Thus, the spineless cactus has been widely cultivated and used for several decades, by enabling the animal feeding in critical periods of year because of its characteristics, morpho‐anatomical and physiological (CAM), which makes it tolerant to long droughts, being a crop that presents high productivity in droughts conditions, when compared to other forages. Nevertheless, the spineless cactus is a crop relatively picky about soil and climate characteristics of region, presenting greater growth in fertile soils, as well as in regions where nighttime temperatures are cool and the air humidity is relatively high. Although the crop be adapted to long droughts periods, many times it’s necessary to perform irrigation in its production system, mainly in regions of low rainfall, for to supply its water needs, thus ensuring productivity and survival of crop. Therefore, the knowledge of characteristics of plant, as well as of appropriate management techniques to crop, is essential for the good performance of spineless cactus.",book:{id:"5978",slug:"new-perspectives-in-forage-crops",title:"New Perspectives in Forage Crops",fullTitle:"New Perspectives in Forage Crops"},signatures:"Wilma Cristina Cavalcante dos Santos Sá, Edson Mauro Santos,\nJuliana Silva de Oliveira and Alexandre Fernandes Perazzo",authors:[{id:"139631",title:"Dr.",name:"Edson Mauro",middleName:null,surname:"Santos",slug:"edson-mauro-santos",fullName:"Edson Mauro Santos"},{id:"180036",title:"Dr.",name:"Juliana",middleName:null,surname:"Oliveira",slug:"juliana-oliveira",fullName:"Juliana Oliveira"},{id:"203022",title:"MSc.",name:"Wilma",middleName:null,surname:"Sá",slug:"wilma-sa",fullName:"Wilma Sá"},{id:"207265",title:"Dr.",name:"Alexandre",middleName:null,surname:"Perazzo",slug:"alexandre-perazzo",fullName:"Alexandre Perazzo"}]},{id:"57115",doi:"10.5772/intechopen.70345",title:"Best Management Practices (BMPs) for Nitrogen Fertilizer in Forage Grasses",slug:"best-management-practices-bmps-for-nitrogen-fertilizer-in-forage-grasses",totalDownloads:1575,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"There is a concern about the growing population and limitation in natural resources which are taking the population to direct its agricultural systems into a more productive and efficient activity, looking to avoid a negative impact on the surrounding environment. The industry energy expended to produce nitrogen (N)-fertilizer is considered an indirect consumption of energy in agriculture, which is higher with an increasing forage yield. Nitrogen is the key nutrient associated with high-yielding production in forage grass and grain crops. The aim of this chapter is to introduce the best management practices (BMPs) for N-fertilizer application in forage grasses to improve N-use efficiency, since the most economical way to feed livestock is forage plants where its potential biomass production is not well explored. The BMPs basically follow three management practices: (1) soil nutrient availability and forage requirement, (2) fertilizer application, and (3) decrease in nutrient losses from soil. In order to take a decision on applying N-fertilizer to accomplish forage grasses production with social, economic, and environmental benefits, the N-fertilizer use in forage grasses is going to follow the “Right rate, Right source, Right place, and Right time (4R) nutrient stewardship.” The application of the 4R’s nutrients stewardship is directly associated with economic, social, and environmental impact. The capacity of the 4R’s implementation worldwide turns into a best guide to improve the striving of better N-use efficiency in forage grass. The 4R’s are interrelated; thus, the recommendation of N-fertilizer rates cannot be prescribed without the combination of the 4R’s where a whole system to be followed should be considered to decide about N-fertilizer in pasture. Consequently, any decision in one of the 4R’s is going to affect the expected N-fertilizer results and dry matter production.",book:{id:"5978",slug:"new-perspectives-in-forage-crops",title:"New Perspectives in Forage Crops",fullTitle:"New Perspectives in Forage Crops"},signatures:"Ademar Pereira Serra, Marlene Estevão Marchetti, Elisângela Dupas,\nSimone Candido Ensinas, Elaine Reis Pinheiro Lourente, Eulene\nFrancisco da Silva, Roberto Giolo de Almeida, Carla Eloize Carducci\nand Alessandra Mayumi Tokura Alovisi",authors:[{id:"182258",title:"Dr.",name:"Ademar",middleName:"Pereira",surname:"Serra",slug:"ademar-serra",fullName:"Ademar Serra"}]},{id:"56079",doi:"10.5772/intechopen.69760",title:"Alfalfa and Its Symbiosis Responses to Osmotic Stress",slug:"alfalfa-and-its-symbiosis-responses-to-osmotic-stress",totalDownloads:1504,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"Alfalfa (Medicago sativa L.) is one of the most cultivated forage legumes in Morocco thanks to its great adaptation to the climatic conditions of this country, its high protein content and its ability to fix atmospheric nitrogen in symbiosis with rhizobia. Environmental stresses such as drought and salinity constitute a major factor limiting the symbiotic nitrogen fixation and legume productivity. In the last decades, this process has interested scholars in understanding the implication of these strains in legume stress tolerance in order to make these symbioses more efficient under difficult conditions. Seed osmopriming is a great technique in the amelioration of seed germination and seedlings growth in responses to several abiotic stress conditions. In this chapter, the effects of water deficit on the Moroccan alfalfa populations and their symbiotic association with rhizobia were discussed. Besides, osmopriming could make these symbioses more efficient especially under stress conditions.",book:{id:"5978",slug:"new-perspectives-in-forage-crops",title:"New Perspectives in Forage Crops",fullTitle:"New Perspectives in Forage Crops"},signatures:"Mohammed Mouradi, Mohamed Farissi, Abdelaziz Bouizgaren,\nYahya Lahrizi, Ahmed Qaddoury and Cherki Ghoulam",authors:[{id:"204044",title:"Dr.",name:"Mohammed",middleName:null,surname:"Mouradi",slug:"mohammed-mouradi",fullName:"Mohammed Mouradi"}]},{id:"58077",doi:"10.5772/intechopen.72310",title:"Sustainable Pasture Management",slug:"sustainable-pasture-management",totalDownloads:1983,totalCrossrefCites:0,totalDimensionsCites:3,abstract:"Grasslands which are a major part of the global ecosystem, covering 37% of the earth’s terrestrial area, have a significant contribution to food security through providing most of the energy and proteins required by the ruminants used for meat and dairy production. Grasslands are considered to have the potential to play a fundamental role in climate change mitigation, particularly regarding carbon storage and sequestration and for biodiversity preservation. This chapter provides an overview of the causes of the pasture degradation and some essential elements for sustainable management, which aims to improve the quantity and quality of pasture, mitigation of climate change and biodiversity preservation. Another point of this chapter is the grasslands with high nature value that nowadays is a top priority in the European legislation as the European Commission has confirmed that HNV farming will remain a key priority in 2014–2020. We present the situation in Bulgaria because it is one of the first member state countries that have assessed HNV regions and put funding in place to support them.",book:{id:"5978",slug:"new-perspectives-in-forage-crops",title:"New Perspectives in Forage Crops",fullTitle:"New Perspectives in Forage Crops"},signatures:"Atanas Sevov, Chtistina Yancheva and Yanka Kazakova",authors:[{id:"220128",title:"Dr.",name:"Christina",middleName:"Georgieva",surname:"Yancheva",slug:"christina-yancheva",fullName:"Christina Yancheva"},{id:"220129",title:"Dr.",name:"Atanas",middleName:null,surname:"Sevov",slug:"atanas-sevov",fullName:"Atanas Sevov"},{id:"222141",title:"Dr.",name:"Yanka",middleName:null,surname:"Kazakova",slug:"yanka-kazakova",fullName:"Yanka Kazakova"}]}],mostDownloadedChaptersLast30Days:[{id:"58077",title:"Sustainable Pasture Management",slug:"sustainable-pasture-management",totalDownloads:1983,totalCrossrefCites:0,totalDimensionsCites:3,abstract:"Grasslands which are a major part of the global ecosystem, covering 37% of the earth’s terrestrial area, have a significant contribution to food security through providing most of the energy and proteins required by the ruminants used for meat and dairy production. Grasslands are considered to have the potential to play a fundamental role in climate change mitigation, particularly regarding carbon storage and sequestration and for biodiversity preservation. This chapter provides an overview of the causes of the pasture degradation and some essential elements for sustainable management, which aims to improve the quantity and quality of pasture, mitigation of climate change and biodiversity preservation. Another point of this chapter is the grasslands with high nature value that nowadays is a top priority in the European legislation as the European Commission has confirmed that HNV farming will remain a key priority in 2014–2020. We present the situation in Bulgaria because it is one of the first member state countries that have assessed HNV regions and put funding in place to support them.",book:{id:"5978",slug:"new-perspectives-in-forage-crops",title:"New Perspectives in Forage Crops",fullTitle:"New Perspectives in Forage Crops"},signatures:"Atanas Sevov, Chtistina Yancheva and Yanka Kazakova",authors:[{id:"220128",title:"Dr.",name:"Christina",middleName:"Georgieva",surname:"Yancheva",slug:"christina-yancheva",fullName:"Christina Yancheva"},{id:"220129",title:"Dr.",name:"Atanas",middleName:null,surname:"Sevov",slug:"atanas-sevov",fullName:"Atanas Sevov"},{id:"222141",title:"Dr.",name:"Yanka",middleName:null,surname:"Kazakova",slug:"yanka-kazakova",fullName:"Yanka Kazakova"}]},{id:"56856",title:"Polyembryony in Maize: A Complex, Elusive, and Potentially Agronomical Useful Trait",slug:"polyembryony-in-maize-a-complex-elusive-and-potentially-agronomical-useful-trait",totalDownloads:1427,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Polyembryony (PE) is a rare phenomenon in cultivated plant species. Since nineteenth century, several reports have been published on PE in maize. Reports of multiple seedlings developing at embryonic level in laboratory and studies under greenhouse and field conditions have demonstrated the presence of PE in cultivated maize (Zea mays L.). Nevertheless, there is a lack of knowledge about this phenomenon; diverse genetic mechanisms controlling PE in maize have been proposed: Mendelian inheritance of a single gene, interaction between two genes and multiple genes are some of the proposed mechanisms. On the other hand, the presence of two or more embryos per seed confers higher nutrimental quality because these grains have more crude fat and lysine than normal maize kernels. As mentioned above, there is a necessity for more studies about PE maize in order to establish the genetic mechanism responsible for this phenomenon; on the other hand, previous studies showed that PE has potential to generate specialized maize varieties with yield potential and grain quality.",book:{id:"6166",slug:"maize-germplasm-characterization-and-genetic-approaches-for-crop-improvement",title:"Maize Germplasm",fullTitle:"Maize Germplasm - Characterization and Genetic Approaches for Crop Improvement"},signatures:"Mariela R. Michel, Marisol Cruz-Requena, Marselino C. Avendaño-\nSanchez, Víctor M. González-Vazquez, Adriana C. Flores-Gallegos,\nCristóbal N. Aguilar, José Espinoza-Velázquez and Raúl Rodríguez-\nHerrera",authors:[{id:"67240",title:"Prof.",name:"Cristobal",middleName:null,surname:"Aguilar",slug:"cristobal-aguilar",fullName:"Cristobal Aguilar"},{id:"183439",title:"Dr.",name:"Raul",middleName:null,surname:"Rodriguez-Herrera",slug:"raul-rodriguez-herrera",fullName:"Raul Rodriguez-Herrera"},{id:"185302",title:"Dr.",name:"Mariela R.",middleName:null,surname:"Michel",slug:"mariela-r.-michel",fullName:"Mariela R. Michel"},{id:"185304",title:"Dr.",name:"Adriana Carolina",middleName:null,surname:"Flores Gallegos",slug:"adriana-carolina-flores-gallegos",fullName:"Adriana Carolina Flores Gallegos"},{id:"217785",title:"Dr.",name:"Marisol",middleName:null,surname:"Cruz-Requena",slug:"marisol-cruz-requena",fullName:"Marisol Cruz-Requena"},{id:"217786",title:"Mr.",name:"Marcelino",middleName:null,surname:"Avendaño-Sanchez",slug:"marcelino-avendano-sanchez",fullName:"Marcelino Avendaño-Sanchez"},{id:"217787",title:"Mr.",name:"Victor",middleName:null,surname:"González-Vazquez",slug:"victor-gonzalez-vazquez",fullName:"Victor González-Vazquez"},{id:"217788",title:"Dr.",name:"Jose",middleName:null,surname:"Espinoza-Velázquez",slug:"jose-espinoza-velazquez",fullName:"Jose Espinoza-Velázquez"}]},{id:"56029",title:"Production of Spineless Cactus in Brazilian Semiarid",slug:"production-of-spineless-cactus-in-brazilian-semiarid",totalDownloads:1875,totalCrossrefCites:4,totalDimensionsCites:8,abstract:"The term “spineless cactus” is used in Brazil to designate cultivars of Opuntia ficus indica Mill and Nopalea cochenillifera Salm Dyck. The spineless cactus was consolidated in Brazilian semiarid as a strategic fundamental food resource in several production livestock systems, constituting a plant with enormous productive potential. Thus, the spineless cactus has been widely cultivated and used for several decades, by enabling the animal feeding in critical periods of year because of its characteristics, morpho‐anatomical and physiological (CAM), which makes it tolerant to long droughts, being a crop that presents high productivity in droughts conditions, when compared to other forages. Nevertheless, the spineless cactus is a crop relatively picky about soil and climate characteristics of region, presenting greater growth in fertile soils, as well as in regions where nighttime temperatures are cool and the air humidity is relatively high. Although the crop be adapted to long droughts periods, many times it’s necessary to perform irrigation in its production system, mainly in regions of low rainfall, for to supply its water needs, thus ensuring productivity and survival of crop. Therefore, the knowledge of characteristics of plant, as well as of appropriate management techniques to crop, is essential for the good performance of spineless cactus.",book:{id:"5978",slug:"new-perspectives-in-forage-crops",title:"New Perspectives in Forage Crops",fullTitle:"New Perspectives in Forage Crops"},signatures:"Wilma Cristina Cavalcante dos Santos Sá, Edson Mauro Santos,\nJuliana Silva de Oliveira and Alexandre Fernandes Perazzo",authors:[{id:"139631",title:"Dr.",name:"Edson Mauro",middleName:null,surname:"Santos",slug:"edson-mauro-santos",fullName:"Edson Mauro Santos"},{id:"180036",title:"Dr.",name:"Juliana",middleName:null,surname:"Oliveira",slug:"juliana-oliveira",fullName:"Juliana Oliveira"},{id:"203022",title:"MSc.",name:"Wilma",middleName:null,surname:"Sá",slug:"wilma-sa",fullName:"Wilma Sá"},{id:"207265",title:"Dr.",name:"Alexandre",middleName:null,surname:"Perazzo",slug:"alexandre-perazzo",fullName:"Alexandre Perazzo"}]},{id:"57540",title:"Impacts of Nitrogen Fertilization and Conservation Tillage on the Agricultural Soils of the United States: A Review",slug:"impacts-of-nitrogen-fertilization-and-conservation-tillage-on-the-agricultural-soils-of-the-united-s",totalDownloads:1288,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"This review evaluated the effects of nitrogen (N) fertilization and conservation tillage systems on SOC stocks. N fertilizer additions had significant positive impact on SOC content, but the magnitude of this effect differed as a result of varying cropping systems: as cropping intensity increased, measured SOC content between fertilized and control treatment also increased. Significant differences of measured SOC stocks were detected between no till and conventional till, as well as reduced till and conventional till. However, no significant difference was observed between reduced till and no till. The differences of measured SOC content between no till and conventional till appeared to be significantly associated with treatment duration. Crop rotation system, soil texture, and mean annual precipitation did not have significant effects on SOC stocks produced from conventional tillage to no till. The results of this study confirmed that adoption of N fertilizer additions and conservational tillage systems can contribute to increased SOC level and thereby have the potential to mitigate the enhanced greenhouse gas effect. However, the evaluation of net carbon dioxide mitigation potential of these two recommended management practices should be carried out under a full carbon cycle analysis from carbon input to carbon output.",book:{id:"6166",slug:"maize-germplasm-characterization-and-genetic-approaches-for-crop-improvement",title:"Maize Germplasm",fullTitle:"Maize Germplasm - Characterization and Genetic Approaches for Crop Improvement"},signatures:"Meimei Lin",authors:[{id:"208050",title:"Dr.",name:"Meimei",middleName:null,surname:"Lin",slug:"meimei-lin",fullName:"Meimei Lin"}]},{id:"79507",title:"Improving Maize Shelling Operation Using Motorized Mobile Shellers: A Step towards Reducing Postharvest Losses in Low Developing Countries",slug:"improving-maize-shelling-operation-using-motorized-mobile-shellers-em-a-step-towards-reducing-postha",totalDownloads:181,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Maize shelling is still a challenge in low developing countries with more efforts required to advance this operation. In Uganda, motorized immobile maize shellers have been fabricated locally to enhance the shelling operation. However, their performance has not elated the farmers. The unsatisfactory performance is a result of these shellers being fabricated by local artisan with finite understanding of the maize grain characteristics and operation factors to optimize maize shelling. In addition, farmers in these countries have a deficiency of power to operate the motorized maize shellers available. Transportation of these motorized maize shellers is also still a challenge and it imposes an extra cost to the farmers hence reducing their profits from maize growing. In this chapter, we reviewed maize shelling process in low developing countries particularly the categories of maize shelling, maize sheller design requirements, use of equations to design sheller parts, modification of the motorized maize shellers and case studies on the mobile maize shellers, comparing them with immobile maize shellers. The study concluded that on addition to other sheller performance attributes, motorized mobile maize shellers can solve transportation challenges associated with motorized immobile maize shellers.",book:{id:"11016",slug:"maize-genetic-resources-breeding-strategies-and-recent-advances",title:"Maize Genetic Resources",fullTitle:"Maize Genetic Resources - Breeding Strategies and Recent Advances"},signatures:"Denis Nsubuga, Isa Kabenge, Ahamada Zziwa, Nicholas Kiggundu, Joshua Wanyama and Noble Banadda",authors:[{id:"425479",title:"Ph.D. Student",name:"Denis",middleName:null,surname:"Nsubuga",slug:"denis-nsubuga",fullName:"Denis Nsubuga"},{id:"436644",title:"Dr.",name:"Isa",middleName:null,surname:"Kabenge",slug:"isa-kabenge",fullName:"Isa Kabenge"},{id:"436645",title:"Dr.",name:"Ahamada",middleName:null,surname:"Zziwa",slug:"ahamada-zziwa",fullName:"Ahamada Zziwa"},{id:"436646",title:"Dr.",name:"Nicholas",middleName:null,surname:"Kiggundu",slug:"nicholas-kiggundu",fullName:"Nicholas Kiggundu"},{id:"436647",title:"Dr.",name:"Joshua",middleName:null,surname:"Wanyama",slug:"joshua-wanyama",fullName:"Joshua Wanyama"},{id:"436648",title:"Dr.",name:"Noble",middleName:null,surname:"Banadda",slug:"noble-banadda",fullName:"Noble Banadda"}]}],onlineFirstChaptersFilter:{topicId:"305",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:99,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:290,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:12,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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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. 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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,annualVolume:11404,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,annualVolume:11405,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. 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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. 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Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. 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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:"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:"Beijing University of Technology",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:"Lakhno Igor Victorovich 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.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of 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 a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), 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 DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. 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: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{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:"243698",title:"M.D.",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:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{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:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZkkQAG/Profile_Picture_2022-05-09T12:55:18.jpg",biography:null,institutionString:null,institution:null},{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:"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. 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We welcome chapters presenting research on the many applications of multi-agent studies including, but not limited to, the following key areas: machine learning for multi-agent systems; modeling swarms robots and flocks of UAVs with multi-agent systems; decision science and multi-agent systems; software engineering for and with multi-agent systems; tools and technologies of multi-agent systems.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/27.jpg",keywords:"Collaborative Intelligence, Learning, Distributed Control System, Swarm Robotics, Decision Science, Software Engineering"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:{id:"25",title:"Environmental Sciences",doi:"10.5772/intechopen.100362",issn:"2754-6713",scope:"\r\n\tScientists have long researched to understand the environment and man’s place in it. The search for this knowledge grows in importance as rapid increases in population and economic development intensify humans’ stresses on ecosystems. Fortunately, rapid increases in multiple scientific areas are advancing our understanding of environmental sciences. Breakthroughs in computing, molecular biology, ecology, and sustainability science are enhancing our ability to utilize environmental sciences to address real-world problems.
\r\n\tThe four topics of this book series - Pollution; Environmental Resilience and Management; Ecosystems and Biodiversity; and Water Science - will address important areas of advancement in the environmental sciences. They will represent an excellent initial grouping of published works on these critical topics.
\r\n\tPollution is caused by a wide variety of human activities and occurs in diverse forms, for example biological, chemical, et cetera. In recent years, significant efforts have been made to ensure that the environment is clean, that rigorous rules are implemented, and old laws are updated to reduce the risks towards humans and ecosystems. However, rapid industrialization and the need for more cultivable sources or habitable lands, for an increasing population, as well as fewer alternatives for waste disposal, make the pollution control tasks more challenging. Therefore, this topic will focus on assessing and managing environmental pollution. It will cover various subjects, including risk assessment due to the pollution of ecosystems, transport and fate of pollutants, restoration or remediation of polluted matrices, and efforts towards sustainable solutions to minimize environmental pollution.
",annualVolume:11966,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/38.jpg",editor:{id:"110740",title:"Dr.",name:"Ismail M.M.",middleName:null,surname:"Rahman",fullName:"Ismail M.M. Rahman",profilePictureURL:"https://mts.intechopen.com/storage/users/110740/images/2319_n.jpg",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"201020",title:"Dr.",name:"Zinnat Ara",middleName:null,surname:"Begum",fullName:"Zinnat Ara Begum",profilePictureURL:"https://mts.intechopen.com/storage/users/201020/images/system/201020.jpeg",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorThree:null,editorialBoard:[{id:"252368",title:"Dr.",name:"Meng-Chuan",middleName:null,surname:"Ong",fullName:"Meng-Chuan Ong",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRVotQAG/Profile_Picture_2022-05-20T12:04:28.jpg",institutionString:null,institution:{name:"Universiti Malaysia Terengganu",institutionURL:null,country:{name:"Malaysia"}}},{id:"63465",title:"Prof.",name:"Mohamed Nageeb",middleName:null,surname:"Rashed",fullName:"Mohamed Nageeb Rashed",profilePictureURL:"https://mts.intechopen.com/storage/users/63465/images/system/63465.gif",institutionString:null,institution:{name:"Aswan University",institutionURL:null,country:{name:"Egypt"}}},{id:"187907",title:"Dr.",name:"Olga",middleName:null,surname:"Anne",fullName:"Olga Anne",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBE5QAO/Profile_Picture_2022-04-07T09:42:13.png",institutionString:null,institution:{name:"Klaipeda State University of Applied Sciences",institutionURL:null,country:{name:"Lithuania"}}}]},{id:"39",title:"Environmental Resilience and Management",keywords:"Anthropic effects, Overexploitation, Biodiversity loss, Degradation, Inadequate Management, SDGs adequate practices",scope:"\r\n\tThe environment is subject to severe anthropic effects. Among them are those associated with pollution, resource extraction and overexploitation, loss of biodiversity, soil degradation, disorderly land occupation and planning, and many others. These anthropic effects could potentially be caused by any inadequate management of the environment. However, ecosystems have a resilience that makes them react to disturbances which mitigate the negative effects. It is critical to understand how ecosystems, natural and anthropized, including urban environments, respond to actions that have a negative influence and how they are managed. It is also important to establish when the limits marked by the resilience and the breaking point are achieved and when no return is possible. The main focus for the chapters is to cover the subjects such as understanding how the environment resilience works, the mechanisms involved, and how to manage them in order to improve our interactions with the environment and promote the use of adequate management practices such as those outlined in the United Nations’ Sustainable Development Goals.
",annualVolume:11967,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/39.jpg",editor:{id:"137040",title:"Prof.",name:"Jose",middleName:null,surname:"Navarro-Pedreño",fullName:"Jose Navarro-Pedreño",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRAXrQAO/Profile_Picture_2022-03-09T15:50:19.jpg",institutionString:"Miguel Hernández University of Elche, Spain",institution:null},editorTwo:null,editorThree:null,editorialBoard:[{id:"177015",title:"Prof.",name:"Elke Jurandy",middleName:null,surname:"Bran Nogueira Cardoso",fullName:"Elke Jurandy Bran Nogueira Cardoso",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRGxzQAG/Profile_Picture_2022-03-25T08:32:33.jpg",institutionString:"Universidade de São Paulo, Brazil",institution:null},{id:"211260",title:"Dr.",name:"Sandra",middleName:null,surname:"Ricart",fullName:"Sandra Ricart",profilePictureURL:"https://mts.intechopen.com/storage/users/211260/images/system/211260.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}}]},{id:"40",title:"Ecosystems and Biodiversity",keywords:"Ecosystems, Biodiversity, Fauna, Taxonomy, Invasive species, Destruction of habitats, Overexploitation of natural resources, Pollution, Global warming, Conservation of natural spaces, Bioremediation",scope:"