Cognitive domains affected in NF1.
\r\n\tThis book will intend to look at different migrant patterns, voluntary and involuntary migration, over the last three centuries. What influenced people to leave their home countries, family, and friends and settle somewhere else? The book may include histories of the 19th century, consider tragedies and movements activated by political events in the 20th century, and/or look at recent events of the 21st century. Push and pull factors are important points. While most of us may be influenced in a negative way by the current happenings in Eastern Europe, the Russian invasion and resulting tragedies also demonstrate some very positive human traits – the preparedness of Ukraine’s surrounding countries to help those in need and to provide a safe place for the present.
\r\n\tWhether one looks at voluntary or involuntary migration into any country, after a period of adjustment, migrants do play a positive role. The research found that migrants contribute to the economy (food, shelter, employment, tax) and enrich a country’s cultural norms. Prerequisites for successful settlements are that the host society adopts a tolerant approach and that the migrants recognize the law and the language of the host country. Nothing is ever easy or without controversy, but I am a migrant (German Australian), and life in Australia has been relatively harmonious. Issues that could be considered in the book are multicultural societies (do monocultural societies still exist?) and theories of acculturation versus integration (settlement processes).
\r\n\tTwo further issues are very important in relation to human migration. There is climate change, global warming, and the environment, which clearly affect people’s movement. Small island populations are very concerned about rising sea levels. 2021 has also seen floods costing human lives: Turkey (August 2021), Brazil (December 2021), Chile (January 2021), and South India (November 2021), to name but a few. In Australia (March 2022), farms and whole townships in New South Wales and Queensland have been flooded for the second time in five years, and plans to resettle these towns are considered. Official and social media provide ample coverage of the events, which leads me to the next issue. There is today’s very important role of the media, of the official and social media. We are constantly bombarded with images of human war tragedies and flood victims. People in industrialized, western countries must be the best-informed populace. How far do the images and up-to-date TV news influence us, make us change our behavior, and perhaps even consider us more generous than we have been?
\r\n\tClimate change and the media are relatively new to the human migration debate, but both issues play important parts, and some interesting discussions are appreciated.
\r\n\t
Neurofibromatosis is a collection of three distinct autosomal dominant genetic disorders including neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis. Each of these disorders has their own genetic variant, symptoms, and disease course [1]. These disorders are neurocutaneous syndromes, which represent a group of central nervous system (CNS) disorders with simultaneous lesions of other organs such as the skin or eye. One core common symptom among these conditions is that they cause tumors of nerve sheath [2].
\nIn this chapter, we discuss cognitive, academic, and adaptive effects of neurofibromatosis over the course of the lifespan. Through review and synthesis of the extant literature, we summarize what is currently known regarding cognitive sequelae associated with neurofibromatosis and discuss the functional impact with regard to learning, academics, and overall quality of life (QoL). Neurofibromatosis is a multisystem disorder that can cause multiple nerve sheath tumors throughout the body [1]. Each of the three conditions present with their own distinct as well as overlapping symptoms that can have a negative impact on QoL (e.g., chronic pain, bone abnormalities, skin disorders, hearing problems, and learning disabilities) [3, 4]. The presence of benign and malignant tumors, depending on their presentation and treatment regimen, can impact cognitive and developmental functioning [1]. Understanding the functional impact of this disorder is especially crucial in order to improve quality of life throughout the lifespan, as there is no known cure for neurofibromatosis [3]. NF1 is one of the most prevalent and researched genetic disorders. In contrast, prevalence rates of NF2 and Schwannomatosis are much lower, and related research is much more limited. As such, this chapter will focus on the most common of the genetic conditions, NF1.
\nNF1 is characterized by cutaneous symptoms, including café-au-lait spots, skin neurofibromas, bone abnormalities (e.g., scoliosis), and glial cell tumors (gliomas) [2]. It is associated with a range of developmental and cognitive issues that are present throughout the lifespan. Cognitive and learning problems are the most common complications associated with NF1 [5, 6, 7]. In contrast, we did not find any studies that directly investigate the cognitive impact and learning issues of NF2 or Schwannomatosis. This is likely in part because these conditions are less prevalent and believed not to be directly associated with learning issues or academic struggles. That said, these are multisystem conditions that can impact vision and hearing, which can have indirect impact on cognitive skills and learning. Thus, we will discuss the cognitive effects of NF2 and Schwannomatosis indirectly by looking at associated common symptoms of the disorders that can impact cognition. NF2 is defined by bilateral vestibular schwannomas (i.e., benign Schwann cell tumors on the vestibulocochlear nerve), which can cause hearing loss and balance issues [1]. Schwannomatosis is the newest recognized form of neurofibromatosis and is characterized by multiple schwannomas that typically occur in adulthood [1]. The degree of physical/medical phenotypical symptom presentation of each of these conditions is highly variable [1, 3]. Not surprisingly, the cognitive impact of these disorders has been found to be just as variable, which will be discussed more in detail below. At this time, the current literature does not demonstrate to what extent specific cognitive skills are related to each NF phenotype, and it is not yet known whether the presence of predisposing genetic factors for each variant of NF explain this heterogeneity of cognitive outcomes.
\nBecause the phenotypic expression of NF1 is so variable, some individuals living with NF1 are unaware they have the disorder while others are significantly impacted. Additionally, symptoms and signs of NF1 can be fluid and can change in presentation throughout a person’s life [8]. In more severe presentations, NF1 can cause physical disfigurement and can be accompanied by significant neurological problems, such as brain tumor and seizures [2]. As noted above, NF1 is a disorder that affects multiple systems in the body, including the brain.
\nThere have been many studies that have investigated the cognitive and learning issues associated with NF1 across age groups throughout the lifespan. One reason that the cognitive and learning struggles associated with NF1 have been well-researched is that NF1 is a single gene disorder (i.e., a mutation of the tumor suppressor gene on chromosome 17), and as such it presents an opportunity to investigate cognitive dysfunction at the molecular and cellular level [9]. The NF1 gene encodes the neurofibromin protein, which serves a vital role in regulating the development of the brain [10]. Brain abnormalities have been detected in magnetic resonance imaging (MRI) studies of those with NF1, such as increased white matter volume, increased subcortical gray matter volume in the thalamus right caudate, decreased cortical gray matter density, T2 hyperintensities (T2H), macrocephaly, and reduced integrity of white matter microstructure [11, 12, 13]. Research has also indicated that thalamic T2H as well as volume abnormalities in the corpus callosum, putamen, and amygdala are specifically associated with cognitive deficits in NF1 [11, 14]. Of note, studies looking into the number of T2 spots and how this relates to cognitive impairment have been inconsistently documented [15].
\nMedical complications that can co-occur with NF1 may lead to or compound cognitive deficits. For example, children with oncological complications of NF1 (e.g., brain tumors) are at risk for long-term cognitive issues as a result of treatment with chemotherapy and/or cranial irradiation [16]. Optic gliomas, tumors that arise from the nerve sheath of the optic nerve, are fairly common in children with NF1 and are sometimes associated with visual impairment, which can impact cognitive skills. The presence of a brain tumor also increases the risk of seizures or additional tumors arising in other areas of the brain [17], which can lead to specific cognitive deficits dependent on the area of the brain it is impacting. NF1 has also been associated with increased rates of other rarer neurological conditions that have known cognitive effects, including cortical dysplasia and hemimegalencephaly, as well as cerebrovascular diseases such as Moyamoya syndrome [17, 18, 19].
\nJust as the severity of phenotypic expression and incidences of medical symptoms are quite variable within those with NF1, the impact on the CNS and subsequent cognitive and academic functioning are significantly heterogeneous. Cognitive and academic weaknesses are some of the most common symptoms in NF1 [5, 6, 7]. Cognitive weaknesses can present challenges for the individual, and this has been shown to occur across the lifespan [7]. Findings from studies with very young children have noted that developmental delays and subsequent academic struggles and learning disabilities are pervasive [12, 20]. With regard to investigations with adults and elderly adults, cognitive weaknesses have been noted to be fairly stable over time from childhood [6, 21, 22]. Overall, the level and type of functional impairment may vary depending on what period in life an individual is in (e.g., preschool, school aged, college, working adult, elderly). Across age groups, cognitive issues associated with NF1 have significant associated morbidities, including weaker adaptive skills [15]. Additional consequences of cognitive difficulties associated with NF1 include poorer academic achievement and overall reduced QoL [3].
\nBelow we will provide an in-depth discussion on the cognitive morbidities associated with NF1 as indicated by current research. Table 1 summarizes specific cognitive domains and findings related to the NF1 population, including overall intellectual ability as well as underlying cognitive functions including language, nonverbal skills, memory, attention, executive functions, academic skills, and adaptive skills.
\nDomain | \nDefinition | \nCommon findings | \n
---|---|---|
Intellectual ability (IQ) | \nSummary score of overall cognitive/reasoning ability | \nMultiple studies suggest IQ to be mildly reduced (IQ ~ 90) | \n
Language | \nHow well a person expresses (including speech) and understands language | \nStudies have varied. Weaknesses with expressive language and speech are more common than receptive language issues Limited studies in adults. | \n
Nonverbal skills | \nVisual spatial and fluid reasoning skills | \nWeaknesses are very common; however, recent studies suggest that findings are confounded by executive function demands inherent in nonverbal measures | \n
Memory | \nLearning and retention of information | \nStudies on explicit memory have been variable. Weakness with working memory (short term memory) are common | \n
Attention | \nAbility to focus, maintain focus on a task | \nMultiple studies have noted attention problems to be very common. Up to 70% of children demonstrate deficit(s) in one or more aspect of attention | \n
Executive functioning | \nA collection of higher order skills that assist with complex goal directed behavior | \nWeaknesses are common. Specific weaknesses with planning/organization and working memory | \n
Academic skills | \nSkills learned in school that include reading, writing, and mathematics | \nWeaknesses are very common. Studies vary in prevalence from 20 to 75%, which appears in part to how learning problems are defined | \n
Adaptive skills | \nBasic skills needed for independent living | \nMildly reduced, similar to IQ above | \n
Cognitive domains affected in NF1.
Studies investigating specific cognitive domains as they relate to NF1 have been wide ranging in their outcomes. Early on, it was believed that in childhood, NF1 was associated with a “nonverbal learning disability” (NLD) profile, a former term for what encompasses deficits in visual–spatial, fine motor, and handwriting abilities in the context of preserved verbal functioning [23]; however, later research challenged this notion with findings indicating that features of NLD are inconsistent among NF1 populations [24, 25]. Additionally, the comorbidity of learning difficulties with these deficits has been found to significantly vary [6, 24]. This is likely in part due to the heterogeneity of the clinical presentation of the condition as well as methodological issues used in research studies, including differences in approaches to cognitive measurement and how learning problems are operationally defined.
\nAdditional studies examining the cognitive outcomes associated with NF1 have led to mixed findings and indicate varying degrees of prevalence of cognitive and academic problems. Hyman et al. [6] noted that these issues were likely due to research design factors, such low sample sizes, lack of controls, subject and control selection, as well as how learning problems are operationally defined. Individual cognitive test sensitivity and measures with overlapping cognitive domains have also been identified as leading to variability [26]. For example, performance on a commonly used visuospatial task in the assessment of nonverbal skills in children, the Rey-Osterrieth Complex Figure Test [27], can be undermined by weaknesses in attention and executive functions, as well as motor demands on the measure. Studies have varied in findings related to the prevalence of cognitive issues associated with NF1, though most note that cognitive issues are quite prevalent. Hyman et al. [6] noted that 81% of their sample had moderate to severe cognitive issues in one or more cognitive domains.
\nIntellectual ability is a cognitive construct that is commonly measured by an Intelligence Quotient (IQ), which represents an individual’s performance on an intelligence test relative to similar-aged individuals and culminates performance across verbal and nonverbal problem-solving skills. [28] IQ represents what Charles Spearman (1904) proposed in the early 20th century as the
Numerous studies have investigated IQ in NF1 populations. One of the more consistent cognitive findings in NF1 in children is that overall IQ is slightly lower than the normal population. That is, studies investigating IQ have placed the mean overall IQ approximately 10 points lower than normative sample [6, 29, 30]. This finding has been documented when compared to siblings controlling for environmental influences [30]. Hyman et al. [6] compared cognitive performance of 81 children with NF1 to 49 sibling controls. They found that the NF1 group demonstrated mildly reduced FSIQ with a mean of 90.6 compared to sibling mean of 102.6. Interestingly, this study found no associations between IQ and clinical severity, familial history of NF1, gender or age. Socioeconomic status was the only significant predictor of IQ in NF1 in their sample. Mild delays in IQ have also been noted with very young children, and given that difficulties have been found to be stable across the lifetime, this pattern has been noted in adults as well [14, 31]. In a combined adult and pediatric sample of 103 patients with NF1, Ferner et al. [32] noted an overall mean IQ score of 88.6 [32]. This finding appears to be consistent across cultures. Descheemaeker et al. found the overall IQ to be 89.96 in a Dutch-speaking sample [21]. With regard to elderly adults, there is very limited research investigating NF1; however, one small study noted mild delays in overall intellectual ability [22]. Taken together, these studies provide further support for the lack of progressive decline in IQ over time in NF1. In summary, it appears that NF1 is associated with average but mildly reduced overall IQ , which appears stable over the course of a lifespan.
\nDespite overall average intelligence, NF1 is associated with greater prevalence of intellectual disability. Intellectual Disability (ID), formerly known as Mental Retardation, is defined in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) as an IQ approximately two standard deviations below the population mean with associated deficits in adaptive functioning [33]. Studies have varied on findings related to the actual prevalence of ID in NF1 populations. Early studies were believed to have significantly overestimated the prevalence of ID due to methodological issues as well as how ID was defined [5]. The rate of ID in NF1 is believed to be 6–7%, which is much less than what was previously believed, though still two to three times the normative expectation [6]. The prevalence of ID increases if neurological complications (brain tumor, seizures) are not excluded [34].
\nThe overall composite score of the Full-Scale IQ likely masks the underlying subtle cognitive profile of NF1. Nearly 80% of people with NF1 have some cognitive deficit [14]. Thus, recent studies have focused on more discrete cognitive domains which we will discuss more below.
\nVerbal skills are a collection of cognitive processes that involves language. Language is commonly divided into expressive and receptive language, which is how well a person uses language to relay their thoughts and ideas (including use of speech) and how a person understands language, respectively.
\nWeaknesses with aspects of language have been found in populations with NF1. Delays in early language development have been noted children as young as 10 months, which appear to persist [20, 35, 36]. NF1 has been associated with weaknesses with nearly all aspects of language; however, studies have not been consistent [37, 38]. Expressive language problems, especially with speech/articulation, have been more consistently found than deficits with receptive language. Additional speech issues include problems with prosody, overall voice qualify, and aspects of speech sounds [37]. Hyman et al. [6] found that 44% of children with NF1 in their sample received speech-language therapy. Batista et al. [36] assessed central auditory temporal function in children with NF1 and correlated it with the results of language testing. They compared 25 NF1 patients to 22 healthy controls on audiometric and language tasks. They found no problems with peripheral acoustic hearing; however, the NF1 group performed more poorly on the temporal auditory processing task. Weaknesses with phonological skills in children have also been documented in several studies [38, 39, 40]. Phonological skills are not only associated with language delays but are also a core component of reading disability, which will be discussed further below. Studies on children have documented further weaknesses with verbal concept formation and comparisons as measured by the Similarities subtest from the Wechsler Intelligence Scales for Children (WISC). These findings were consistent compared to normal population and sibling control group [37, 41]. However, studies with childhood populations have not been consistent, as some studies noted that the differences in language disappear when IQ is controlled for [6, 38]. Verbal fluency has been found to be a relatively preserved cognitive function in children [42, 43]. Available literature on language in adult and elderly adult populations is relatively scarce as most studies in NF1 have been with pediatric populations.
\nNonverbal skills are a collection of visual perceptual, visual spatial, or visual-motor skills. They include visual perception, understanding spatial relations, and ability to integrate information from visual stimulus. Visuospatial (also referred to as visuoperceptual) skills have been found to be impaired in most studies involving children [5, 6, 12, 24, 26, 29, 34]. These studies have noted specific deficits in angulation, visual organization, and object recognition. The findings have been consistent when comparing children to normative sample or sibling control.
\nEarly studies on children with NF1 noted a significant discrepancy between verbal and nonverbal reasoning abilities. Weaknesses were noted with nonverbal reasoning skills, while verbal skills were believed to be preserved [25, 44]. However, several follow-up studies did not find the same discrepancy between verbal IQ and perceptual (nonverbal) IQ [6, 25]. Hyman et al. [6] actually noted a pattern opposite of what was expected, with males with NF1 having weaker verbal than nonverbal reasoning compared to females with NF1. It is now clear that NF1 is condition that can impact a range of cognitive functions not limited to nonverbal reasoning.
\nIn addition to nonverbal reasoning, studies with children and adults suggest weaknesses with many aspects of nonverbal skills including visual perception, visual-motor integration, form discrimination, visual organization [6, 21, 41, 42]. Indeed, weaknesses with aspects of visual spatial skills are common in NF1. However, several studies have not found significant differences between NF1 and controls regarding aspects of nonverbal skills [38, 45, 46]. Van Eylen et al. reviewed studies that directly assessed visuoperceptual and visual spatial functioning of children with NF1 [26]. They argue that the measures used to assess nonverbal skills are likely confounding findings. That is, many tasks that are purported to assess nonverbal skills also require other cognitive domains, most notably executive functions. In their sample, they found that when controlling for executive functions and IQ , performance on nonverbal tasks was not impaired. A similar pattern of weaknesses on nonverbal tasks has been documented in adults [21]. Overall, it appears that NF1 is associated with weaker visual/nonverbal skills; however, there are many confounds to previous studies which temper this conclusion.
\nMemory is our ability to encode, store, and retrieve previously learned information. Neuroscientists have identified many forms of memory, which at a basic level is divided into explicit and implicit memory. Cognitive tests of memory often only assess a small portion of memory functions. Cognitive tests typically focus on working memory and explicit memory. Working memory is our ability to actively hold information in mind for a short duration. It is commonly conceptualized as part of a collection of higher order executive functions.
\nCognitive tests assess explicit memory with verbal and visual tests. Studies in both children and adults identifying memory weaknesses in NF1 have been variable, and several studies have not found a significant difference in memory performance than controls [6, 21, 37, 41]. Hyman et al. [6] did not find a significant difference in performance on verbal and visual explicit memory tests in children with NF1 compared to sibling controls. Similarly, Krab et al. [41] did not find a significant difference in NF1 children’s performance on verbal or visual memory tasks when compared to children with no learning disabilities, children with specific learning disabilities, and children with general learning disabilities. In contrast, several studies have documented explicit memory weakness in children with NF1 [10, 14, 44, 47]. Bulgheroni et al. [47] assessed visual memory with the Rey Complex Figure Test (RCFT) [48]. They compared 18 children with NF1 to 17 siblings and 18 typically developing children. They found that the children with NF1 performed worse on recall memory, with no difference found regarding recognition memory. This pattern suggests that the NF1 had more difficulty with efficient retrieval rather coding and storing of the information, which is often due how the information was initially organized (an executive function). Overall, studies on explicit memory are mixed.
\nAttention involves of collection of processes that allows a person to engage in certain cognitive processing while ignoring others [51]. Attention is a complex system that has many subcomponents that includes focused attention, sustained attention, divided attention, and selective attention.
\nCognitive weakness with attention is very common to children, adolescents, and adults with NF1 [7, 37]. Children with NF1 have frequently been reported to exhibit impaired performance on tasks measuring the ability to sustain and switch attention [6, 52]. These findings appear to be consistent across measures of both visual and auditory sustained attention, as well as divided auditory attention and response inhibition [53]. In a large cohort study of 199 children with NF1, approximately 54% were at risk for inattentive behavior based on parent and teacher ratings [43].
\nUp to 50% of individuals with NF1 meet diagnostic criteria for attention-deficit hyperactivity disorder (ADHD), [37, 54] and research has indicated that incidence rates of ADHD are much more common in children with NF1 than in immediate family members [55]. Neurocognitive deficits associated with NF1 have been found to be more severe in individuals with comorbid ADHD. While both groups have been found to demonstrate deficits in sustained attention, individuals with NF1 and comorbid ADHD have been indicated to be at higher risk [10]. Reduced attention skills in children with NF1 and ADHD have also been found to negatively impact the ability to process and respond to verbal instructions of increasing complexity, suggesting that receptive language skill development may also be vulnerable in this group as a result of attentional difficulties [10].
\nThe behavioral phenotype of ADHD in NF1 also appears to differ from ADHD in the general population. In a large cohort study by Hyman et al. [6], ADHD co-occurrence in children with NF1 occurred equally in frequency among males and females, which differs from the 3:1 ratio of males to females in the general population [43]. Research suggests that ADHD in NF1 also differs from typical ADHD in that the combined subtype appears to occur at the highest frequency followed by the inattentive subtype, while the hyperactive/impulsive subtype is typically found at the highest rates in children with ADHD alone [56]. Additionally, while clinical symptoms of ADHD in children with NF1 and those diagnosed with ADHD are comparable, differences lie in performance deficits specific to each group such that response inhibition processes have been found to be compromised in ADHD, but not in NF1 when compared to healthy controls, suggesting that response inhibition deficits may be less strong compared to those occurring in ADHD [57]. It has also been suggested that NF1/ADHD is not associated with increased frequency of executive deficits related to behavioral inhibition as it is in the general ADHD population [6]. A study comparing individuals with NF1/ADHD with a group of participants with ADHD and no NF1 found that ADHD symptomatology in NF1 did not exacerbate attention deficits and suggested that ADHD cannot account for all attention impairments in NF1 [57].
\nVarious brain-based characteristics associated with NF1 have been presumed to contribute to the neurocognitive deficits in NF1. For example, increased brain volume due to increased white matter and an enlarged corpus callosum appear to be characteristic of children with NF1 and may interfere with integration and processing of information [56]. Regarding attentional processes specifically, an fMRI study investigating ventral attention networks in the brain found that children with NF1 demonstrated hypoactivation in the temporoparietal junction and the anterior cingulate cortex when compared to typically developing children, which was associated with poorer selective attention and attentional control [58].
\nThe presence of attentional deficits in children with NF1 is associated with even greater risk for poorer performance in other cognitive functions, learning, social skills, and academic achievement [12, 56]. Social outcomes in particular appear to be worse in this group than in children with NF1 only [56]. A study examining face perception in children with NF1 found that sustained attention to faces in a social context is reduced in this population, which may inhibit the processing of socially relevant information needed for successful reciprocal social interactions [59]. Research also suggests that the risk of developing a specific learning disorder is higher in children with NF1 who have a diagnosis of ADHD [6]. As with other domains, it is suggested that while the literature on attentional problems primarily investigates these issues in childhood, these difficulties likely persist into adulthood without treatment.
\nExecutive functions include a wide range of higher-order cognitive processes that serve goal-directed behaviors, including working memory, planning, organization, inhibition, flexibility. Because executive functioning encompasses a wide range of processes, studies investigating executive functioning in individuals with NF1 vary greatly in terms of the areas of focus and measures used [37]. Of note, many neuropsychological measures of executive function have been found to lack correlation with functional/behavioral ratings of the same constructs when evaluating individuals with NF1, and it has been suggested that Behavior Rating Inventory of Executive Function (BRIEF) rating scale items are more predictive of performance in real-world tasks outside of the structured testing environment [43]. Children with NF1 demonstrate significant impairments across all composite scores on the BRIEF [43, 52]. Differences remained even after controlling for VIQ [43].
\nDespite this, executive dysfunction has been noted on performance measures as well. Beaussart et al. [50] conducted a meta-analysis of executive functioning in children with NF1. They included 19 studies in their analysis, with a total of 805 children with NF1 and 667 control subjects. They found a moderate effect with executive functions, indicating that children with NF1 had greater overall executive functioning impairments than controls. However, they noted variability in sub-domains of executive functions including cognitive flexibility, planning and problem solving, inhibitory control, and working memory. They found significant effect sizes for each sub-domain, with moderate effect sizes for working memory and planning/organization and small effect sizes for cognitive flexibility and inhibition. Significance remained even after controlling for moderating variables of executive functioning measures, control group composition, IQ , and ADHD.
\nWeaknesses with working memory in NF1 populations are much more consistent and prevalent than with explicit memory. Several studies have documented verbal and visual working memory weaknesses [10, 14, 49]. Beaussart et al. [50] found a moderate to large effect size for working memory problems. The effect size for verbal working memory was larger than nonverbal working memory. They note that differences in effect size may be due to the psychometric properties of the working memory tasks [50].
\nExecutive function deficits have also been distinguished in NF1 adult populations. In particular, weaknesses in working memory and cognitive flexibility have been noted [21]. Very limited information is known with regard to executive functions in the elderly. Costa de et al. [22] noted working memory weaknesses in this population; however, this study was limited by a very small NF1 group.
\nAcademic learning entails the use of basic educational skills to be successful in the classroom. This includes reading, writing, and mathematics. Academic learning struggles are one of the most common concerns of parents of children with NF1 [54]. Estimates of learning disabilities have significantly varied between studies. Research has found prevalence rates of learning difficulties to be 20–70% [5, 6, 41]. The variability is in part due to how each study operationalized the definition of “learning disability,” as the definition of learning disability has changed over the years. Previously an IQ-academic discrepancy model in which an individual performing much more poorly in an academic skill as compared to his or her overall intelligence level was used to define learning disability; however, this limited definition of a specific learning disability has received increased scrutiny and is rarely used today [60]. Hyman et al. [6] found that 20% of their child sample met the strict definition (discrepancy model) of specific learning disability (SLD), which is double the rate found in the normal population. In contrast, Krab et al. [41] used a different definition that examined “learning efficacy” and found that 75% percent of their sample had learning difficulties based on this definition. This study also noted a connection between disease severity and increase in learning struggles; however, this pattern has not been consistent in other studies. They argue that this is due to the fact that other studies do not systematically measure severity and other methodological issues.
\nDespite the disagreement in overall prevalence rates of learning struggles, studies have been consistent in that NF1 is associated with significantly higher rate of learning disabilities in children when compared to normative sample and sibling controls [5, 6, 38, 41].
\nSpecific learning disability in the area of reading has been noted in childhood NF1 populations. Weaknesses have been found regarding phonological awareness, word decoding, fluency, and reading comprehension [5, 38, 39, 54]. Cutting and Levine [38] compared four groups that included children without reading difficulties, a reading disability group, an NF1 group without reading disability, and an NF1 group with reading disability. They found that children with NF1 with reading struggles performed similarly as the reading disability group.
\nLearning struggles in mathematics and written expression in children with NF1 have also been noted. Math difficulties have been noted with computation and application of math concepts [6, 41, 49, 54]. Krab et al. [41] found that 23% of their NF1 sample met the criteria for a specific learning disability in mathematics and 77% demonstrated learning efficiency struggles with mathematics. However, another study did not find learning disability in mathematics [46]. Problems with writing including graphomotor control (penmanship) and spelling have noted as well [49, 61].
\nAdaptive skills are a collection of functional behaviors needed to effectively meet the demands of our environment. Adaptive functions are often divided into Conceptual skills, Practical skills, and Social skills. The DSM-V notes that adaptive deficits result in the failure to meet developmental and social standard for independent living without support.
\nSeveral studies have noted adaptive deficits in children with NF1 [15, 62]. In a cross sectional study of 104 children with NF1, Eby et al. [15] found that 46.5 percent of their sample demonstrated adaptive functioning impairment. They found mild reductions across Conceptual, Social and Practical skill domains. Less is known about the specific adaptive domains that are impacted in adults and elderly adults. While adaptive demands change as individuals develop across the lifespan, it is likely that because cognitive difficulties remain stable with age, adaptive deficits are associated with adults with NF1 as well.
\nWe were unable to locate any studies that directly investigate cognitive weaknesses in NF2 or Schwannomatosis populations. It is likely that this has not been investigated, as these disorders are rarer and typically have less brain involvement. As such, we will discuss the cognitive effects of NF2 and Schwannomatosis with regard to common symptoms associated with these disorders and how these symptoms may impact cognitive functions.
\nNF2 is defined in part by bilateral vestibular schwannomas [63]. Vestibular schwannomas are nonmalignant tumors that arise from eighth cranial nerve. The vestibular schwannomas can impact hearing, balance, at times vision, and facial weakness [65]. Hearing loss is progressive due to the presence of schwannomas and treatment, and it has been found in 60% of adults and 30% of children with NF2 [65]. Hearing loss can lead to decreased QoL [66] and can impact language development. Hearing loss has also been associated with decreased performance on intellectual and academic skills [67, 68]. Olivier et al. [69] investigated sensorineural hearing loss associated with intellectual and learning struggles in children with brain tumors. They found that children with severe hearing loss demonstrated greater difficulty with reading with weaker phonological skills, processing speed, and reading [69].
\nSchwannomatosis is clinically distinguished from NF2 by the lack of bilateral vestibular schwannomas and ependymomas [64]. All neurofibromatoses, including NF1, NF2, and schwannomatosis, have schwannomas. Depending on the size and location, schwannomas can also be associated with pain [3]. Chronic pain has been associated with cognitive weaknesses with memory, attention, processing speed, and executive functions [70]. More research is needed to determine the possible cognitive sequalae associated with NF2 and Schwannomatosis. Further research is also warranted to distinguish whether differences in these sequelae exist depending on the age of the individual.
\nNeurofibromatosis is associated with effects on cognitive domains that impact learning, adaptive functioning, and quality of life across the lifespan of individuals affected by these disorders. The three distinct genetic disorders that encompass neurofibromatosis have their own genetic variant, symptoms, and disease course that result in differences in phenotypic expression as well as impact on the brain. While patterns of neurocognitive outcomes vary among and within each disorder, relatively less research has been conducted on those with NF2 and Schwannomatosis as compared to NF1. In particular, more research is needed investigating cognitive sequalae associated with NF2 and Schwannomatosis as these conditions at least indirectly are associated with cognitive weaknesses which can impact overall quality of life, likely from diagnosis through late adulthood.
\nWithin NF1, cognitive deficits are much more common yet highly variable within and between individuals. The heterogeneity of the cognitive outcomes is likely due to a combination of reasons, including genetic factors that have not been adequately elucidated yet, as well as methodological issues. Current research does not yet indicate to what extent differences among each NF phenotype are related to differences in typical cognitive deficits associated with each genetic variant. Common methodological issues in the literature include composition of control groups, evolving/varying definitions of cognitive domains and learning disorders, and limitations inherent in specific cognitive tests. Nonetheless, the current literature indicates that IQ , expressive language, visual spatial and fluid reasoning, and working memory are commonly impacted to some extent. Attention and executive functions appear to also be compromised in individuals with NF1, which are a factor in difficulties in receptive language, memory, academic skills, and adaptive skills. Most studies are focused on children, though existing adult studies suggest that cognitive deficits are present and similar to child studies, likely due to the stability of difficulties over time. Overall, evaluation of cognitive skills in those with neurofibromatosis is important in order to determine the functional impact that potential deficits may have on an individual, especially with regard to academic performance and adaptive functioning. This is especially significant due to the fact that neurofibromatosis is not a curable condition, which necessitates treatment that directly targets cognitive, academic, and adaptive problems directly. Regular monitoring of these individuals with respect to cognitive skills can aid in necessary intervention planning and should occur as early as possible to detect and treat issues that can arise early in development.
\nThe authors have no conflict of interest.
Due to anatomical location and function, esophageal motility disorders, inflammatory diseases, gastroesophageal reflux (GER), esophageal rings and webs, tumors and other esophageal conditions and diseases can cause many extraesophageal symptoms, which are increasingly recognised and diagnosed by otolaryngologists, pulmonologists, cardiologists, and, of course, gastroenterologists. Certain pathophysiological conditions that are not localized in the esophagus may be the first symptoms of esophageal disease or signs associated with the onset of esophageal disease. One of the etiological factors is the pathophysiological mechanism of the increase in intra-abdominal pressure that occurs during weight gain and in pregnancy. Another etiological factor is the pathophysiological mechanism of relaxation of the lower esophageal sphincter that may occur due to coronary heart disease drug therapy rich in nitrates. A similar thing happens during antirheumatic therapy in rheumatoid arthritis and some degenerative diseases of the locomotor system. Other conditions that may be associated with gastroesophageal reflux and esophageal diseases include diabetes mellitus, which results in prolonged gastric stagnation and consequent prolonged gastric emptying, and duodenal ulcer, duodenal stenosis, or malignant gastric disease in which delayed gastric emptying is present. So far, it is a well-known fact that the appropriate speed of food passage through the gastrointestinal tract, which is conditioned by a series of autoregulatory processes, is important. An optimal rate of passage is required - small enough to complete food digestion and absorption of substances and large enough to supply the body with the necessary nutrients in a timely manner [1]. The most common atypical symptoms of esophageal disease, primarily esophagitis and gastroesophageal reflux disease (GERD), will be listed here. For better visibility and easier understanding, the classification of atypical extraesophageal symptoms was performed according to the criterion of anatomical localization (Figure 1):
otolaryngological manifestations
thoracic manifestations
cardiac manifestations
Extraesophageal manifestation of esophageal diseases.
And last but not least, the biopsychosocial dimensions of esophageal diseases and extraesophageal symptoms are being recognized, too.
Patients with reflux laryngitis often have characteristic anamnestic data and records in the history of the disease. Common symptoms of laryngitis include chronic or intermittent recurrent cough, chronic sore throat, hoarseness, clearing of the throat, dry mouth, feeling of a ‘lump’ and tickling in the throat, nocturnal dyspnea, laryngospasm and dyspepsia. Inspection of the laryngeal mucosa may reveal erythema and edema of the mucosa covering the arytenoid cartilage, the posterior part of the larynx, and often the posterior part of the true vocal cords.
Two theories explain the pathogenesis of reflux laryngitis:
theory of direct injury of the laryngeal mucosa and surrounding tissue by acid and pepsin;
reflex theory [2].
Due to direct injury to the laryngeal and pharyngeal mucosa, mucociliary transport is damaged and secretions accumulate in the throat, which causes additional irritation of the mucosa and contributes to the symptoms of postnasal drip, throat clearing and foreign body sensation in the throat. As the larynx lacks the protective external cleansing and salivary mechanisms that neutralize acid, gastric reflux remains undiluted for a long time, resulting in tissue injury. The action of pepsin leads to the depletion of the carbonic anhydrase isoenzyme III, and it catalyzes the reversible hydration of carbon dioxide resulting in the production of bicarbonate ions. The formation of bicarbonate ions directly neutralizes the acidic stomach contents and inactivates pepsin, so the ions actually protect the tissue from acid refluxate [3, 4]. On the other hand, depletion of carbonic anhydrase isoenzyme III reduces the neutralization of acidic gastric contents and allows its prolonged activity. According to the reflex theory, laryngopharyngeal reflux occurs due to esophageal reflux that stimulates vagal-mediated reflexes, resulting in a subjective need to ‘clear’ the throat and a chronic cough that leads to injury to the laryngeal mucosa. Laryngopharyngeal reflux is a clinical entity that represents the return of gastric contents to the space of the larynx and hypopharynx, which causes the contact of acid with the tissues of the upper aerodigestive tract [5]. In the physiological state, the upper and lower esophageal sphincters act together and prevent reflux of gastric contents into the esophagus and upper aerodigestive tract. Howewer, the pathophysiology of LPR is typically attributed to a defect or dysfunction of the upper esophageal sphincter. The esophagus features a number of protective mechanisms which prevent injury of the mucosa, which the laryngopharyngeal mucosa do not possess, and are more susceptible to damage from acid reflux. Laryngeal epithelium is up to 100 times more susceptible to pepsin damage than esophageal tissue [6]. Regurgitation of the contents may cause primary burning and/or sore throat, cough, need for excessive throat cleansing, and secondarily may cause symptoms such as dysphonia, productive expectoration and globus hystericus (feeling of a ‘lump’ in the throat). Signs of laryngopharyngeal reflux are visible in the form of laryngeal irritations, hyperemic mucosa of the vocal cords and arytenoids, thinned vocal cords, posterior pharyngeal wall abnormalities, erythema, edema, and discontinuity of mucosal continuity. Of these symptoms, laryngeal irritations and abnormalities of the posterior pharyngeal wall have a statistically significant prevalence in patients with reflux. It should be noted that these symptoms, in addition to esophagitis and gastroesophageal reflux disease, are also present in persons exposed to allergens and irritants and in postnasal drip syndrome. Most authors interpret laryngopharyngeal reflux as atypical gastroesophageal reflux, although some authors disagree with this interpretation given the different pathophysiology and symptomatology of these refluxes [7]. It is important to emphasize that the etiology of reflux in laryngopharyngeal and gastroesophageal reflux is not the same, just as the form and circumstances of occurrence are not quite the same. For example, laryngopharyngeal reflux occurs more often during the day in an upright position, while gastroesophageal reflux occurs in a horizontal position and at night, or during sleep. Different body composition of patients with laryngopharyngeal and gastroesophageal reflux [8] was also observed, and published studies show an association between increased body mass index (identified as obesity) and gastroesophageal reflux disease [9] and a statistically significant higher incidence of gastroesophageal reflux disease in patients with registered obesity. In contrast, increased body mass index is not statistically significant in patients suffering from laryngopharyngeal reflux [10, 11]. Reflux associated with laryngeal symptoms is verified by laryngoscopy and 24-hour pH monitoring. Patients with laryngopharyngeal reflux without alarming symptoms are treated empirically with proton pump inhibitors for one to two months. If this type of therapy is effective, according to individual needs, the therapy is extended to six months with the aim of complete healing of the laryngeal and pharyngeal mucosa.
Chronic gastroesophageal reflux is an etiological factor that contributes to the manifestation of laryngeal symptoms, primarily hoarseness. In addition to hoarseness, laryngopharyngeal reflux and laryngitis may occur. Koufman et al. found that 78% of dysphonic patients have gastroesophageal reflux disease [12]. According to Vashana, acid reflux is especially common in singers. The author explains this statement in several facts: muscle activity due to a vocal technique that works against the lower esophageal sphincter; inadequate feeding and sleep dynamics; emotional components and exposure to stressors typical of this profession [13].
More recent studies has reported significant association between gastroesophageal reflux and chronic rhinosinusitis, but the nature of the association is still unknown. Gastroesophageal reflux disease can cause several upper airway symptoms and change the physiology of nasopharyngeal mucosa, while upper airway diseases might also exacerbate GERD symptoms [14]. This associaton can be explained by three physiological mechanisms: the direct effect of acid or acidic vapor in the nasal mucosa, a dysfunction of the autonomous nervous system and the presence of Helicobacter pylori. It is known that the direct contact of the acid with the nasopharyngeal mucosa results in mucosal edema, with reduction of the mucociliary clearance and obstruction of the sinusal ostium. The acid reflux is an uncommon event in the nasopharynx and occurs in only 5% of GERD patients. Autonomic dysfunction, in this case the increase of the vagal tonus, may partly account the hyper-reactivity of the airways to acid. The Heliobacter pylori has been identified in the esophagus, palatine and tonsils, saliva and teeth, and is not known how its presence can result in some abnormalities of this tissues. Retrospective studies describe an improvement of 69 to 89% of the nasosinusal symptoms after GER treatment. Despite this knowlege, it is still not possible to state that the gastroesophageal reflux is one of the leading risk factors to chronic rhinosinuitis, but it must be researched as an unchaining factor when there is no other evident etiology. Howewer, GER symptoms are very prevalent in patients with chronic rhinosinusitis [15].
Chronic otitis media may lead to tympanic membrane perforation as a consequence of unresolved and resistant middle ear infection, blockage of the Eustachian tube, insufficiency of ciliary clearance, or an injury to the ear persisting more than 3 months. Various microorganisms are considered as etiologic agents in COM. Other predisposing factors may also play role in persistence of the disease. Many recent studies have shown a potential association between gastroesophageal reflux and otitis media chronica [16]. Gastroesophageal reflux can be an inflammatory cofactor and can result in upper respiratory tract disorders, including COM in pediatric and adult age group. Otitis media with effusion is the most common cause of hearing loss in children. The pathogenesis is multifactorial: infections, impaired immunologic status, allergic history, anatomical problems, familial predisposition and enviromental factors have role in pathogenesis. The angle and length of the Eustachian tube are more horizontal and shorter in infants than in adults, and may allow reflux of gastric contens from the nasopharynx into the middle ear. It can cause to lay the groundwork for mucociliary clearance dysfunction and bacterial infections. Some studies found pepsin concentrations in samples from middle ear effusions of up to 1000-fold greater in children who undergone myringotomy. It was suggested that the GER may be related to glue ear in children. The therapy of COM is mainly surgical. Higher level of damage in the middle ear of patients having GERD requires appropriate treatment which may positively affect outcomes for COM surgery [17].
More recent studies have pointed out that extraesophageal symptoms of GERD are acidic lesions of the oral mucosa. These lesions are caused by direct acid and pepsin exposure, or acidic vapor contact in the oral cavity. GERD was reported to be associated with microscopic alterations in the palatal mucosa, such as epithelial atrophy, deepening of epithelial crests in connective tissue and a higher prevalence of fibroblasts [18]. Mucosal changes are quite common and not pathognomonic and specific of patients with gastroesophageal or esophagopharyngeal reflux, but erythema of the soft palate and uvula, epithelial atrophy, xerostomia and glositis are quite common in GERD patients. Some authors pointed out the presence of aphtoid lesions, hoarseness, chronic periodontitis, dry oral mucosa with a keratotic appearance of the gingival tissues and the presence of burning mouth. In addition, persons with GERD may complain of a sour or acidic taste, impaired taste (dysgeusia), an oral burning sensation and water brash (flooding of the mouth with saliva in response to an esophageal reflux stimulus) [19]. Adequate mucin-rich salivary secretions coat all of the internal anatomical surfaces and are essential for the protection of the oropharyngeal and esophageal mucosa and the teeth from chemical, thermal, mechanical and microbial damage. Saliva also facilitates efficient swallowing and speech. Some studies have found a significant association between gastroesophageal reflux and hyposalivation. On the other hand, proton pump inhibitors can cause hyposalivation. Hyposalivation may result in xerostomia, impaired mastication and swallowing, painful mouth, cracked lips and angular cheilitis [20].
The quantity of salivation and the quality of saliva can be an indicator of a certain disease of the oropharynx and esophagus or it can be an indicator of the complication of such conditions. Saliva is produced by the parotid, submandibular and sublingual glands and the small salivary glands. Sialoreia usually occurs in neurological diseases, such as Parkinson’s and Wilson’s disease, Angelman’s syndrome, infections, heavy metal poisoning, and can also occur in the secretory phase of the menstrual cycle or as idiopathic paroxysmal sialoreia. Increased salivation can be caused by systemic consumption of drugs with a cholinergic effect (clozapine, risperidone, nitrazepam, lithium and bethanekol), and it also occurs as a subtle manifestation of gastroesophageal reflux disease in the form of ‘water brash’. However, hypersalivation, although uncomfortable and disruptive, does not necessarily have to be negative since saliva plays an important role in protecting the esophageal mucosa. There are studies on the importance of ingested saliva that neutralizes the pH of gastric acid regurgitated into the esophagus [21] and on the buffering of gastric acid that enters the esophagus by reflux [22]. The acid that accumulates in the upper part of the esophagus reflexively initiates the formation of saliva [23], which is not the case when the acid accumulates in the lower part of the esophagus [24].
Chronic regurgitation of gastric acids in patients with gastroesophageal reflux and related condition - laryngopharyngeal reflux may cause dental erosion which can, in combination with attrition or bruxism, lead to extensive loss of coronal tooth tissue. Dental erosion is typically a slowly-progressing and ireversibile phenomenon defined as the loss of tooth substance by chemical processes (acid exposure) not involving bacteria [25]. The literature shows a strong correlation between GERD and dental erosion, with a median prevalence of 24% in a large range of age groups. The degree of erosion due to GERD is related to the duration of the disease, frequency of reflux, the pH and type of acid, and the quality and quantity of saliva. Demineralisation and the loss of calcium and phosphate ions from the mineral surface of the teeth result in visible defects, and cause significant reduction in microhardness which makes the softened surface more prone to mechanical damage [26]. It is recognized that refluxed acid attacks the palatal surfaces of the upper incisor teeth first, later, if the condition continues, erosion of the occlusal surfaces of the posterior teeth in both arches and the labial or buccal surfaces [27].
Halitosis is an unpleasant odor from the oral cavity and is a condition that affects a large number of people [28]. The prevalence of halitosis is 8–46% [29]. The pathophysiological mechanism of halitosis is still not completely clear and is mainly attributed to oral pathology due to microbial activity in the interdental space, between the teeth and periodontium, and on the dorsal side of the tongue. Published data suggest that halitosis may correlate with chronic sinusitis, upper and lower respiratory tract diseases, various systemic diseases, gastroenterological diseases, and consumption of certain drugs in patients without oral pathology. It has been stated that mouth breathing, too, can be the cause of halitosis [30]. Although halitosis has previously been considered a rare consequence of gastrointestinal disorders [31], recent literal data have shown that it is common in gastrointestinal pathology and is significantly more common in patients with gastroesophageal reflux disease than in healthy individuals [32]. Furthermore, the symptom is often present in patients with verified infection with Helicobacter pylori, a bacterium that is among the major pathogenic factors of inflammatory and ulcerative changes on the gastric mucosa [33, 34, 35, 36]. In addition, a high correlation has been demonstrated between halitosis and gastroesophageal reflux disease and peptic ulcer disease [37], and some authors have linked halitosis to volatile sulfur compounds [30, 38, 39] and to the chemical compounds cadaverine, some types of indoles [30]. Cadaverine (1,5-pentanediamine) is a toxic diamine formed by tissue putrefaction. Indole (benzopyrrole) is a heterocyclic compound formed by the breakdown of the amino acid tryptophan in the digestive tract, however, it is also used in the production of certain drugs, fragrances and essential oils [40]. An organic compound from the indole family associated with halitosis is skatol (3-methylindole), which occurs naturally in faeces, it is also present in flowers and essential oils (orange and jasmine) in low concentrations, and is used as a fixative in many perfumes [41]. A 2006 study by Lee et al. reported that Helicobacter pylori produces hydrogen sulfide and methyl mercaptan that contribute to halitosis [42], and the bacterium itself is one of the main factors in the manifestation of gastrointestinal diseases.
Thoracic manifestations can occur secondary to the wide range of esophageal disorders: inflammatory process, infections, trauma and perforation, congenital malformations, esophageal motility disorders and benign and malignant neoplasms. Complications associated with these diseases and disorders can involve the mediastinum, tracheobronchial tree, and lungs. Lower respiratory system and esophagus share a common embryological derivation and are anatomically related. Pulmonary complications can be associated with high morbidity and mortality. Such complications can be categorized as:
mediastinal complications (due to trauma, perforation, foreign bodies, caustic injury, or malignancy);
tracheobronchial complications (congenital or acquired tracheoesophageal fistulas);
pleural complications (esophagopleural fistulas);
lung complications (due to GERD, infectious and inflammatory process) [43].
Gastroesophageal reflux disease has been linked to a variety of respiratory diseases either as a direct cause, or as a risk factor to the inability to control or worsening of the disease. It can cause various pulmonary manifestations and nonspecific complaints: chronic cough and fewer, recurrent pneumonia, noncardiac chest pain, sputum production and dyspnoea, bronchospasm. Epidemiological studies in patients with reflux esophagitis have shown an increased risk for chronic bronchitis, chronic obstructive pulmonary disease, pneumonia, and idiopathic pulmonary fibrosis. Chronic cough and bronchial asthma are more common respiratory manifestations of GERD. Pathological GERD has been described in 30% to 80% of patients with asthma. Micro-aspiration of gastric contents and/or vagal irritation from gastro esophageal reflux may constitute airway irritants and thus represent a potential pathogenic mechanism for acute illness or acute exacerbations of chronic pulmonary diseases. Exacerbations of chronic obstructive pulmonary disease is twice as high in patients with GERD as in those without GERD symptoms. GERD can produce lung disease by two mechanisms: by reflex neural mechanisms occuring during reflux events limited to the lower part of esophagus, and direct from gastric contents refluxed into the pharynx producing upper airway damage and lung disease. While gastroesophageal reflux may increase airways resistance and cause inflammation by releasing pro-inflammatory mediators, esophagopharyngeal reflux creates the potential to aspiration and its consequences which varies depending of the duration, volume and nature of the aspirate [44]. Chronic cough is considered to be a cough that is continuously present for eight weeks and longer. Among the etiological factors, the three most common causes of chronic cough can be singled out: postnasal drip syndrome, asthma and gastroesophageal reflux. In 75% of cases, patients with chronic cough do not have the typical symptoms of esophagitis or gastroesophageal reflux disease, yet the result of 25% of patients with symptoms of both types speaks in favor of the association of chronic cough and esophageal disease [45]. Namely, the determination of correlation is primarily based on the strength and direction of the correlation, and not only on the frequency and percentage of results.
Coronary heart disease and gastroesophageal reflux disease can interact and produce chest pain. Some recent studies have shown that exposure of the esophageal mucosa to acid can compromise myocardial perfusion and cause chest pain by inducing coronary spasm or cardiac dysrythmia [46, 47, 48]. On the other hand, myocardial ischemia can cause esophageal dysmotility or relaxation of the lower esophageal sphincter and exacerbate GERD [49]. GERD can worsen sleep disturbances, and sleep apnea increases the risk of a cardiovascular diseases [50]. These two diseases have a number of common risk factors and comorbidities, such as diabetes, hypertension, hyperlipidemia, smoking and alcoholism, gender and age [51, 52]. Proton pump inhibitors, as a treatment option in GERD therapy can also affect cardiovascular physiology. One of the big population-based study shows that PPI usage can reduce the cardioprotective effects of certain therapies, and it can also reduce the contractility of myocardial tissue and raise the risk of atherosclerosis by increasing the serum levels of homocysteine by impairing the absorption of vitamin B12. This study indicates that GERD is associated with an increased risk of developing coronary heart disease, and PPI therapy that lasts longer than one year might increase the risk of CHD [53].
Esophageal symptoms are common and often overlap between different esophageal disorders, making a diagnosis based solely on patient history, symptoms, and physical presentation challenging. Esophageal motility disorders often manifest with chest pain and dysphagia. Other symptoms are heartburn, regurgitation, weight loss and malnutrition. Chest pain is localized behind the sternum, and does not spread to the shoulders and arms, which distinguishes it from cardiac pain. Gastroesophageal reflux (GER) symptoms have been reported in up to 20% of the adult population, which makes GER one of the common gastrointestinal disorders with a chronic or recurrent nature. Patients often complain of heartburn and acid regurgitation. The presence of this symptoms at least once a week for the last 3 months are considered essential in diagnosis of a clinical disorder called gastroesophageal reflux disease (GERD) [54]. Gastroesophageal reflux is often associated with symptoms of the respiratory tract. Chronic cough of unknown origin, laryngeal complaints, throat discomfort, breathing disorders, bronchitis, pneumonia and even non allergic asthma, resistant to steroid therapy, are suspicious of being reflux related. Other symptoms are haematemesis, eructation, dysphagia, odynophagia, hiccups, changes in the oral, nasal and pharyngeal mucosa, dental erosions and cardiac problems. Laryngopharyngeal reflux (LPR) is present in up to 60% of GERD patients. Symptoms of this multifactorial syndrome are mainly extraesophageal, and are found in the head and neck region. The most common symptoms are cough, hoarseness, dysphonia, sore throat, globus pharyngeus, chronic postnasal drip, and Eustachian tube dysfunction, Some studies have shown that LPR has been associated with vocal cord polyps, vocal cord granulomas, laryngospasm, subglottic stenosis and laryngeal carcinoma [55]. Esophagitis can be caused by reflux mechanism, infections, caustic agents, ionizing radiation, thermal injuries, eating disorders, medications, and as a part of some sistemic diseases. The most common symptoms are dysphagia and odynophagia, heartburn and acid regurgitation, haematemesis. Severe and prolonged vomiting and straining can results in tears in the mucous membrane of the esophagus. This condition is called Mallory-Weiss Syndrome. The main symptoms are hematemesis and melena, and in severe cases heavier bleeding may occur. Ribs and webs are the most common structural abnormalities of the esophagus. Most of them are asymptomatic, but can occasionally present with intermittent dysphagia to solids. They are associated with Zenker’s diverticulum and Plummer-Vinson Syndrome which is classically a triad of dysphagia, iron-deficiency anemia, and esophageal webs. Esophageal rings are almost always associated with a hiatal hernia [56]. The esophagus is the most common site of acute foreign body obstruction. The clinical presentation varies from mild to extremely severe, and the most common symptoms are hypersalivation and odynophagia [57]. Esophageal perforation is a rare and potentially life-threatening condition most commonly caused by manipulations with medical instruments, forced strining and foreign bodies. The most common symptoms are odynophagia, chest pain, vomiting and shortness of breath, and in 70% of patients with perforation of the intrathoracic esophagus there are pleuromediastinum and palpable crepitus in the soft tissue of the neck and thorax. Caustic injuries of the esophagus are potentially one of the most challenging clinical situations in gastroenterology. Caustics and corrosives cause tissue injury by a chemical reaction. The severity of injury and the clinical presentation depends on several aspects: Concentration of the substance, amount ingested, duration of tissue contact, location of damage, and pH of the agent: hoarseness, stridor, dysphagia, odynophagia, hematemesis, epigastric pain. Short-term complications include perforation and death [58, 59]. Esophageal cancer is the sixth most common cause of cancer deaths worldwide. In the initial stage it usually shows no symptoms. The most common symptoms are dysphagia, chest pain, pressure or burning, heartburn, coughing or hoarseness, weight loss, bleeding, and hiccups. As can be seen, almost all esophageal diseases shows atypical and extraesophageal symptomatology. Due to proper and accurate diagnosis and treatment, the cooperation of a multidisciplinary team is required.
We would like to thank Ms. Mirna Brunčić for translating this text.
The authors have no conflict of interest.
The figure is from the author’s own source.
"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges".
\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.
",metaTitle:"About Open Access",metaDescription:"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges.\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.",metaKeywords:null,canonicalURL:"about-open-access",contentRaw:'[{"type":"htmlEditorComponent","content":"The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\\n\\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\\n\\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
\\n\\n“By “open access” to [peer-reviewed research literature], we mean its free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited” (reference: http://www.budapestopenaccessinitiative.org)
\\n\\nOAI-PMH
\\n\\nAs a firm believer in the wider dissemination of knowledge, IntechOpen supports the Open Access Initiative Protocol for Metadata Harvesting (OAI-PMH Version 2.0). Read more
\\n\\nLicense
\\n\\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
\\n\\nPeer Review Policies
\\n\\nAll scientific works are Peer Reviewed prior to publishing. Read more
\\n\\nOA Publishing Fees
\\n\\nThe Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
\\n\\nDigital Archiving Policy
\\n\\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\\n\\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
\\n\\nOpen Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
\\n\\nOpen Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
\\n\\nWe aim at improving the quality and availability of scholarly communication by promoting and practicing:
\\n\\n\\n"}]'},components:[{type:"htmlEditorComponent",content:'
The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\n\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\n\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
\n\n“By “open access” to [peer-reviewed research literature], we mean its free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited” (reference: http://www.budapestopenaccessinitiative.org)
\n\nOAI-PMH
\n\nAs a firm believer in the wider dissemination of knowledge, IntechOpen supports the Open Access Initiative Protocol for Metadata Harvesting (OAI-PMH Version 2.0). Read more
\n\nLicense
\n\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
\n\nPeer Review Policies
\n\nAll scientific works are Peer Reviewed prior to publishing. Read more
\n\nOA Publishing Fees
\n\nThe Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
\n\nDigital Archiving Policy
\n\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\n\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
\n\nOpen Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
\n\nOpen Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
\n\nWe aim at improving the quality and availability of scholarly communication by promoting and practicing:
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The generation of waste is one of the central concerns in urban agglomerations, particularly in the global South, where inadequacies, absences and weaknesses shape the local waste management system. Uneven geographic development has created obvious spaces of exclusion and neglect. In response, informal and organized waste pickers engage in selective waste collection and recycling, serving their community and the environment. These contributions are still mostly unrecognized and unaccounted for. This chapter begins with emphasizing the challenges of urban growth, consumption, poverty and waste. In the global South, every day millions of informal waste pickers reclaim recyclables from household waste to earn their living. In doing so they make an important contribution to reducing the carbon footprint of cities, recovering resources, improving environmental conditions and health creating jobs and income among the poor, particularly in low-income residential areas. This chapter discusses the organization of these initiatives into networks and examines the challenges and benefits of such practices that promote grassroots resilience and contribute to reducing both the adverse impacts of cities on climate and environmental change (UN sustainable development target # 11.6) as well as urban poverty (Goal # 8).",book:{id:"6396",slug:"urban-agglomeration",title:"Urban Agglomeration",fullTitle:"Urban Agglomeration"},signatures:"Jutta Gutberlet",authors:[{id:"188532",title:"Prof.",name:"Jutta",middleName:null,surname:"Gutberlet",slug:"jutta-gutberlet",fullName:"Jutta Gutberlet"}]},{id:"58196",doi:"10.5772/intechopen.72191",title:"The Multivariated Effect of City Cooperation in Land Use Planning and Decision-Making Processes: A European Analysis",slug:"the-multivariated-effect-of-city-cooperation-in-land-use-planning-and-decision-making-processes-a-eu",totalDownloads:1080,totalCrossrefCites:7,totalDimensionsCites:17,abstract:"Spatial and urban planning processes regarding border cooperation have reached unprecedented levels in recent decades, not only due to their potential for territorial integration, i.e., infrastructure construction and planning activities worldwide. Bearing in mind the European project, for a united and strong network of nations, this scenario is more evident in European territories. In this regard, through multivariated analyzes of city cooperation on European border areas, it is possible to identify the factors that influence the territorial success and also a sustainable regional development and even their effects over the urban agglomerations. From the identified factors, the study pointed out one that is common to all cases: connectivity-movement between cities.",book:{id:"6396",slug:"urban-agglomeration",title:"Urban Agglomeration",fullTitle:"Urban Agglomeration"},signatures:"Luís Carlos Loures, Rui Alexandre Castanho, José Manuel Naranjo\nGómez, Ana Vulevic, José Cabezas and Luis Fernández-Pozo",authors:[{id:"108118",title:"Dr.",name:"Luis",middleName:null,surname:"Loures",slug:"luis-loures",fullName:"Luis Loures"},{id:"215340",title:"Dr.",name:"Ana",middleName:null,surname:"Vulevic",slug:"ana-vulevic",fullName:"Ana Vulevic"},{id:"215341",title:"Prof.",name:"José",middleName:null,surname:"Cabezas Fernández",slug:"jose-cabezas-fernandez",fullName:"José Cabezas Fernández"},{id:"215342",title:"Prof.",name:"José Manuel",middleName:null,surname:"Naranjo Gómez",slug:"jose-manuel-naranjo-gomez",fullName:"José Manuel Naranjo Gómez"},{id:"222742",title:"Dr.",name:"Luis",middleName:null,surname:"Fernández-Pozo",slug:"luis-fernandez-pozo",fullName:"Luis Fernández-Pozo"},{id:"290571",title:"Dr.",name:"Rui Alexandre",middleName:null,surname:"Castanho",slug:"rui-alexandre-castanho",fullName:"Rui Alexandre Castanho"}]},{id:"59481",doi:"10.5772/intechopen.73524",title:"Characteristics of Urban Agglomerations in Different Continents: History, Patterns, Dynamics, Drivers and Trends",slug:"characteristics-of-urban-agglomerations-in-different-continents-history-patterns-dynamics-drivers-an",totalDownloads:2823,totalCrossrefCites:6,totalDimensionsCites:14,abstract:"Urban agglomerations show different development patterns and stages. Here, we describe, discuss and compare urban agglomerations in different continents. The introduction section gives a general overview of specific issues of urban agglomerations. Different characteristics in Europe, Asia and America are discussed as experienced by the article’s co-authors, living in or working for urban agglomerations in these continents. First, the history of urbanization and agglomeration evolvement is described, then patterns, functional structures and relations, drivers as well as social and demographic characteristics are discussed (e.g. migration, aging, household structure, housing patterns, workplaces, etc.). Transportation infrastructure (roads, public transport systems) is also addressed as trigger for spatial dynamics causing certain effects (floor space, office and apartment rents releasing urban sprawl or hyper-densification), as well as gentrification. Further topics are urban governance and its impact on agglomeration development. Recent state and future trends will be debated, if important. A conclusion section summarizes the comparison of state, dynamics, drivers and trends.",book:{id:"6396",slug:"urban-agglomeration",title:"Urban Agglomeration",fullTitle:"Urban Agglomeration"},signatures:"Wolfgang Loibl, Ghazal Etminan, Ernst Gebetsroither-Geringer,\nHans-Martin Neumann and Santiago Sanchez-Guzman",authors:[{id:"160720",title:"Dr.",name:"Ernst",middleName:null,surname:"Gebetsroither",slug:"ernst-gebetsroither",fullName:"Ernst Gebetsroither"},{id:"167419",title:"Dr.",name:"Wolfgang",middleName:null,surname:"Loibl",slug:"wolfgang-loibl",fullName:"Wolfgang Loibl"},{id:"214919",title:"MSc.",name:"Ghazal",middleName:null,surname:"Etminan",slug:"ghazal-etminan",fullName:"Ghazal Etminan"},{id:"214920",title:"MSc.",name:"Hans-Martin",middleName:null,surname:"Neumann",slug:"hans-martin-neumann",fullName:"Hans-Martin Neumann"},{id:"214923",title:"MSc.",name:"Santiago",middleName:null,surname:"Sanchez-Guzman",slug:"santiago-sanchez-guzman",fullName:"Santiago Sanchez-Guzman"}]},{id:"46448",doi:"10.5772/58225",title:"Mapping of Ground Deformations with Interferometric Stacking Techniques",slug:"mapping-of-ground-deformations-with-interferometric-stacking-techniques",totalDownloads:3519,totalCrossrefCites:8,totalDimensionsCites:13,abstract:null,book:{id:"3727",slug:"land-applications-of-radar-remote-sensing",title:"Land Applications of Radar Remote Sensing",fullTitle:"Land Applications of Radar Remote Sensing"},signatures:"Paolo Pasquali, Alessio Cantone, Paolo Riccardi, Marco Defilippi,\nFumitaka Ogushi, Stefano Gagliano and Masayuki Tamura",authors:[{id:"168247",title:"Dr.",name:"Paolo",middleName:null,surname:"Pasquali",slug:"paolo-pasquali",fullName:"Paolo Pasquali"},{id:"168811",title:"Mr.",name:"Paolo",middleName:null,surname:"Riccardi",slug:"paolo-riccardi",fullName:"Paolo Riccardi"},{id:"168812",title:"Mr.",name:"Alessio",middleName:null,surname:"Cantone",slug:"alessio-cantone",fullName:"Alessio Cantone"},{id:"168813",title:"Mr.",name:"Marco",middleName:null,surname:"Defilippi",slug:"marco-defilippi",fullName:"Marco Defilippi"},{id:"168814",title:"Mr.",name:"Fumitaka",middleName:null,surname:"Ogushi",slug:"fumitaka-ogushi",fullName:"Fumitaka Ogushi"},{id:"168815",title:"Mr.",name:"Stefano",middleName:null,surname:"Gagliano",slug:"stefano-gagliano",fullName:"Stefano Gagliano"},{id:"170671",title:"Prof.",name:"Masayuki",middleName:null,surname:"Tamura",slug:"masayuki-tamura",fullName:"Masayuki Tamura"}]},{id:"46357",doi:"10.5772/58220",title:"Large Scale Mapping of Forests and Land Cover with Synthetic Aperture Radar Data",slug:"large-scale-mapping-of-forests-and-land-cover-with-synthetic-aperture-radar-data",totalDownloads:4095,totalCrossrefCites:5,totalDimensionsCites:11,abstract:null,book:{id:"3727",slug:"land-applications-of-radar-remote-sensing",title:"Land Applications of Radar Remote Sensing",fullTitle:"Land Applications of Radar Remote Sensing"},signatures:"Josef Kellndorfer, Oliver Cartus, Jesse Bishop, Wayne Walker and\nFrancesco Holecz",authors:[{id:"168830",title:"Dr.",name:"Francesco",middleName:null,surname:"Holecz",slug:"francesco-holecz",fullName:"Francesco Holecz"},{id:"170758",title:"Dr.",name:"Josef",middleName:null,surname:"Kellndorfer",slug:"josef-kellndorfer",fullName:"Josef Kellndorfer"}]}],mostDownloadedChaptersLast30Days:[{id:"57824",title:"Waste in the City: Challenges and Opportunities for Urban Agglomerations",slug:"waste-in-the-city-challenges-and-opportunities-for-urban-agglomerations",totalDownloads:2858,totalCrossrefCites:11,totalDimensionsCites:26,abstract:"Worldwide cities are rapidly expanding, creating visible environmental and social challenges. The generation of waste is one of the central concerns in urban agglomerations, particularly in the global South, where inadequacies, absences and weaknesses shape the local waste management system. Uneven geographic development has created obvious spaces of exclusion and neglect. In response, informal and organized waste pickers engage in selective waste collection and recycling, serving their community and the environment. These contributions are still mostly unrecognized and unaccounted for. This chapter begins with emphasizing the challenges of urban growth, consumption, poverty and waste. In the global South, every day millions of informal waste pickers reclaim recyclables from household waste to earn their living. In doing so they make an important contribution to reducing the carbon footprint of cities, recovering resources, improving environmental conditions and health creating jobs and income among the poor, particularly in low-income residential areas. This chapter discusses the organization of these initiatives into networks and examines the challenges and benefits of such practices that promote grassroots resilience and contribute to reducing both the adverse impacts of cities on climate and environmental change (UN sustainable development target # 11.6) as well as urban poverty (Goal # 8).",book:{id:"6396",slug:"urban-agglomeration",title:"Urban Agglomeration",fullTitle:"Urban Agglomeration"},signatures:"Jutta Gutberlet",authors:[{id:"188532",title:"Prof.",name:"Jutta",middleName:null,surname:"Gutberlet",slug:"jutta-gutberlet",fullName:"Jutta Gutberlet"}]},{id:"59481",title:"Characteristics of Urban Agglomerations in Different Continents: History, Patterns, Dynamics, Drivers and Trends",slug:"characteristics-of-urban-agglomerations-in-different-continents-history-patterns-dynamics-drivers-an",totalDownloads:2823,totalCrossrefCites:6,totalDimensionsCites:14,abstract:"Urban agglomerations show different development patterns and stages. Here, we describe, discuss and compare urban agglomerations in different continents. The introduction section gives a general overview of specific issues of urban agglomerations. Different characteristics in Europe, Asia and America are discussed as experienced by the article’s co-authors, living in or working for urban agglomerations in these continents. First, the history of urbanization and agglomeration evolvement is described, then patterns, functional structures and relations, drivers as well as social and demographic characteristics are discussed (e.g. migration, aging, household structure, housing patterns, workplaces, etc.). Transportation infrastructure (roads, public transport systems) is also addressed as trigger for spatial dynamics causing certain effects (floor space, office and apartment rents releasing urban sprawl or hyper-densification), as well as gentrification. Further topics are urban governance and its impact on agglomeration development. Recent state and future trends will be debated, if important. A conclusion section summarizes the comparison of state, dynamics, drivers and trends.",book:{id:"6396",slug:"urban-agglomeration",title:"Urban Agglomeration",fullTitle:"Urban Agglomeration"},signatures:"Wolfgang Loibl, Ghazal Etminan, Ernst Gebetsroither-Geringer,\nHans-Martin Neumann and Santiago Sanchez-Guzman",authors:[{id:"160720",title:"Dr.",name:"Ernst",middleName:null,surname:"Gebetsroither",slug:"ernst-gebetsroither",fullName:"Ernst Gebetsroither"},{id:"167419",title:"Dr.",name:"Wolfgang",middleName:null,surname:"Loibl",slug:"wolfgang-loibl",fullName:"Wolfgang Loibl"},{id:"214919",title:"MSc.",name:"Ghazal",middleName:null,surname:"Etminan",slug:"ghazal-etminan",fullName:"Ghazal Etminan"},{id:"214920",title:"MSc.",name:"Hans-Martin",middleName:null,surname:"Neumann",slug:"hans-martin-neumann",fullName:"Hans-Martin Neumann"},{id:"214923",title:"MSc.",name:"Santiago",middleName:null,surname:"Sanchez-Guzman",slug:"santiago-sanchez-guzman",fullName:"Santiago Sanchez-Guzman"}]},{id:"58027",title:"Do Degradation of Urban Greenery and Increasing Land Prices Often Come along with Urbanization?",slug:"do-degradation-of-urban-greenery-and-increasing-land-prices-often-come-along-with-urbanization-",totalDownloads:1067,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"In the wake of urbanization, driven by a variety of individual and socio-economic merits, human’s basic residential needs and standard of living may be compromised in the urban areas, as the population agglomerates. However, the knowledge of the associations of urbanization with urban greenery and residential land prices is still in the pursuing process. This empirical research aims to contribute whether the degradation of essential living conditions is a trade-off for the pursued urban life. Hence, Taiwan is selected as the case to analyze the associated relations primarily between 1976 and 2016. The research methods involve descriptive statistics, the panel data analysis, and the cluster analysis. The panel data analysis demonstrates that degraded urban greenery and increasing residential land prices came along with the urbanization in Taiwan between 2001 and 2016. Policy implications include rethinking of the building coverage rate for renewed buildings for more plant-friendly ground, the adoption of building setback policy for more accessible mid-air mini-parks, and avoiding residential units as an investment commodity.",book:{id:"6396",slug:"urban-agglomeration",title:"Urban Agglomeration",fullTitle:"Urban Agglomeration"},signatures:"Yu-hsin Tsai, Jhong-yun Guan and Yu-Hsin Huang",authors:[{id:"215320",title:"Prof.",name:"Yu-Hsin",middleName:null,surname:"Tsai",slug:"yu-hsin-tsai",fullName:"Yu-Hsin Tsai"},{id:"224006",title:"Ms.",name:"Jhong-Yun",middleName:null,surname:"Guan",slug:"jhong-yun-guan",fullName:"Jhong-Yun Guan"},{id:"224007",title:"Ms.",name:"Yu-Hsin",middleName:null,surname:"Huang",slug:"yu-hsin-huang",fullName:"Yu-Hsin Huang"}]},{id:"58922",title:"Promotion of Smart Community Strategy in Vietnam’s Binh Duong Province",slug:"promotion-of-smart-community-strategy-in-vietnam-s-binh-duong-province",totalDownloads:1168,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Vietnam’s Binh Duong Province is located in southeastern Vietnam, immediately to the north of Ho Chi Minh City (HCMC). The province constitutes the southern economic zone of Vietnam, and many Japanese companies—mainly manufacturing enterprises, including small and medium enterprises—are investing there. Becamex IDC Corp (a Vietnamese state-owned developer) and Tokyu Corporation (a Japanese company) established Becamex Tokyu, a joint venture company, in March 2012. As a smart community strategy, Becamex Tokyu is promoting Tokyu Binh Duong Garden City, which is a development plan integrating new urban development. The Becamex Tokyu Bus, which is a wholly owned subsidiary of Becamex Tokyu, operates the new transportation system KAZE Shuttle. In addition, Binh Duong Province has developed a smart community strategy centered on energy establishment in urban development, information and communications technology infrastructure development and utilization, the elimination of physical waste in infrastructure construction, and smart traffic. In this chapter, by using his field work as a basis, the author examines the current status of, and issues faced by, development of the smart community strategy in Binh Duong Province in Vietnam.",book:{id:"6396",slug:"urban-agglomeration",title:"Urban Agglomeration",fullTitle:"Urban Agglomeration"},signatures:"Tetsuro Saisho",authors:[{id:"211195",title:"Dr.",name:"Tetsuro",middleName:null,surname:"Saisho",slug:"tetsuro-saisho",fullName:"Tetsuro Saisho"}]},{id:"46357",title:"Large Scale Mapping of Forests and Land Cover with Synthetic Aperture Radar Data",slug:"large-scale-mapping-of-forests-and-land-cover-with-synthetic-aperture-radar-data",totalDownloads:4095,totalCrossrefCites:5,totalDimensionsCites:11,abstract:null,book:{id:"3727",slug:"land-applications-of-radar-remote-sensing",title:"Land Applications of Radar Remote Sensing",fullTitle:"Land Applications of Radar Remote Sensing"},signatures:"Josef Kellndorfer, Oliver Cartus, Jesse Bishop, Wayne Walker and\nFrancesco Holecz",authors:[{id:"168830",title:"Dr.",name:"Francesco",middleName:null,surname:"Holecz",slug:"francesco-holecz",fullName:"Francesco Holecz"},{id:"170758",title:"Dr.",name:"Josef",middleName:null,surname:"Kellndorfer",slug:"josef-kellndorfer",fullName:"Josef Kellndorfer"}]}],onlineFirstChaptersFilter:{topicId:"636",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:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:317,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517",scope:"Paralleling similar advances in the medical field, astounding advances occurred in Veterinary Medicine and Science in recent decades. These advances have helped foster better support for animal health, more humane animal production, and a better understanding of the physiology of endangered species to improve the assisted reproductive technologies or the pathogenesis of certain diseases, where animals can be used as models for human diseases (like cancer, degenerative diseases or fertility), and even as a guarantee of public health. Bridging Human, Animal, and Environmental health, the holistic and integrative “One Health” concept intimately associates the developments within those fields, projecting its advancements into practice. This book series aims to tackle various animal-related medicine and sciences fields, providing thematic volumes consisting of high-quality significant research directed to researchers and postgraduates. It aims to give us a glimpse into the new accomplishments in the Veterinary Medicine and Science field. 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In brief, we hope that books in this series will provide accessible references for those interested or working in this field and encourage learning in a range of different topics.",coverUrl:"https://cdn.intechopen.com/series/covers/13.jpg",latestPublicationDate:"June 17th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:11,editor:{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",institutionURL:null,country:{name:"Portugal"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"10",title:"Animal Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/10.jpg",isOpenForSubmission:!0,editor:{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. 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From\r\n1964 to 1974, he worked as Assistant in Biochemistry at the School of MedicineUniversidad Nacional de La Plata, Argentina. From 1974 to 1976, he was a Fellowof the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor oBiochemistry at the Universidad Nacional de La Plata, Argentina. He is Member ofthe National Research Council (CONICET), Argentina, and Argentine Society foBiochemistry and Molecular Biology (SAIB). His laboratory has been interested for manyears in the lipid peroxidation of biological membranes from various tissues and different species. Professor Catalá has directed twelve doctoral theses, publishedover 100 papers in peer reviewed journals, several chapters in books andtwelve edited books. Angel Catalá received awards at the 40th InternationaConference Biochemistry of Lipids 1999: Dijon (France). W inner of the Bimbo PanAmerican Nutrition, Food Science and Technology Award 2006 and 2012, South AmericaHuman Nutrition, Professional Category. 2006 award in pharmacology, Bernardo\r\nHoussay, in recognition of his meritorious works of research. Angel Catalá belongto the Editorial Board of Journal of lipids, International Review of Biophysical ChemistryFrontiers in Membrane Physiology and Biophysics, World Journal oExperimental Medicine and Biochemistry Research International, W orld Journal oBiological Chemistry, Oxidative Medicine and Cellular Longevity, Diabetes and thePancreas, International Journal of Chronic Diseases & Therapy, International Journal oNutrition, Co-Editor of The Open Biology Journal.",institutionString:null,institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},editorTwo:null,editorThree:null},{id:"12",title:"Human Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",isOpenForSubmission:!0,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. He is a physiologist working in the field of skeletal muscle. He was awarded his sports science diploma in 1995 by the University of Tsukuba and began his scientific work at the Department of Physiology, Aichi Human Service Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. His interest later turned to the molecular mechanism and attenuating strategy of sarcopenia (age-related muscle atrophy). His opinion is to attenuate sarcopenia by improving autophagic defects using nutrient- and pharmaceutical-based treatments.",institutionString:null,institution:{name:"Tokyo Institute of Technology",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"331519",title:"Dr.",name:"Kotomi",middleName:null,surname:"Sakai",slug:"kotomi-sakai",fullName:"Kotomi Sakai",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000031QtFXQA0/Profile_Picture_1637053227318",biography:"Senior researcher Kotomi Sakai, Ph.D., MPH, works at the Research Organization of Science and Technology in Ritsumeikan University. She is a researcher in the geriatric rehabilitation and public health field. She received Ph.D. from Nihon University and MPH from St.Luke’s International University. Her main research interest is sarcopenia in older adults, especially its association with nutritional status. Additionally, to understand how to maintain and improve physical function in older adults, to conduct studies about the mechanism of sarcopenia and determine when possible interventions are needed.",institutionString:null,institution:{name:"Ritsumeikan University",institutionURL:null,country:{name:"Japan"}}},editorThree:null},{id:"13",title:"Plant Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/13.jpg",isOpenForSubmission:!0,editor:{id:"332229",title:"Prof.",name:"Jen-Tsung",middleName:null,surname:"Chen",slug:"jen-tsung-chen",fullName:"Jen-Tsung Chen",profilePictureURL:"https://mts.intechopen.com/storage/users/332229/images/system/332229.png",biography:"Dr. Jen-Tsung Chen is currently a professor at the National University of Kaohsiung, Taiwan. He teaches cell biology, genomics, proteomics, medicinal plant biotechnology, and plant tissue culture. 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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. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. 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. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"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:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:null},{id:"7227",title:"Dr.",name:"Hiroaki",middleName:null,surname:"Matsui",slug:"hiroaki-matsui",fullName:"Hiroaki Matsui",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Tokyo",country:{name:"Japan"}}},{id:"318905",title:"Prof.",name:"Elvis",middleName:"Kwason",surname:"Tiburu",slug:"elvis-tiburu",fullName:"Elvis Tiburu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"336193",title:"Dr.",name:"Abdullah",middleName:null,surname:"Alamoudi",slug:"abdullah-alamoudi",fullName:"Abdullah Alamoudi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"318657",title:"MSc.",name:"Isabell",middleName:null,surname:"Steuding",slug:"isabell-steuding",fullName:"Isabell Steuding",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"318656",title:"BSc.",name:"Peter",middleName:null,surname:"Kußmann",slug:"peter-kussmann",fullName:"Peter Kußmann",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"338222",title:"Mrs.",name:"María José",middleName:null,surname:"Lucía Mudas",slug:"maria-jose-lucia-mudas",fullName:"María José Lucía Mudas",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}}]}},subseries:{item:{id:"87",type:"subseries",title:"Economics",keywords:"Globalization, Economic integration, Growth and development, International trade, Environmental development, Developed countries, Developing countries, Technical innovation, Knowledge management, Political economy analysis, Banking and financial markets",scope:"
\r\n\tThe topic on Economics is designed to disseminate knowledge around broad global economic issues. Original submissions will be accepted in English for applied and theoretical articles, case studies and reviews about the specific challenges and opportunities faced by the economies and markets around the world. The authors are encouraged to apply rigorous economic analysis with significant policy implications for developed and developing countries. Examples of subjects of interest will include, but are not limited to globalization, economic integration, growth and development, international trade, environmental development, country specific comparative analysis, technical innovation and knowledge management, political economy analysis, and banking and financial markets.
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He has advised, among others, the United Nations Development Program, Inter-American Development Bank, Organization of American States, Pre-investment Organization of Latin America and the Caribbean, Technical Cooperation of the Suisse Government, and the World Bank. Dr. Ortiz is the author, co-author, or editor of books, book chapters, textbooks, research monographs and technical reports, and refereed journal articles. He is listed in Who’s Who in the World, Who’s Who in America, Who’s Who in Finance and Business, Who’s Who in Business Higher Education, Who’s Who in American Education, and Who’s Who Directory of Economists. Dr. Ortiz has been a Fulbright Scholar and an MSI Leadership Fellow with the W.K. Kellogg Foundation. 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