\r\n\tAtherosclerosis is a systemic disease. Some 60% of patients with peripheral artery disease will have ischaemic heart disease, and 30% have cerebrovascular disease. Within five years of diagnosis, 10-15% of patients with intermittent claudication will die from cardiovascular disease. Therefore, management begins with the identification and modification of risk factors that are common to peripheral artery disease, heart disease, and stroke. Treatment goals include reducing cardiovascular risk and improving functional capacity. Revascularization is indicated for persistent symptoms.
\r\n\tThe main objective of the book is to deal with peripheral arterial disease in the most diverse aspects. Addressing issues such as pathophysiology, signs and symptoms, clinical aspects, treatment, and prognosis.
\r\n\t
Obstructive Sleep Apnea (OSA) was described as early as 1837 in “The Posthumous Papers of the Pickwick Club”. Dickens, a British author, described “Joe”, the main character, as a fat boy who falls asleep easily and involuntarily (Figure 1). [1]
Artist (Hablot Knight Browne- Phiz) rendering of Joe, Charles Dickens’ character.
Later on, Osler (1914) used the term “Pickwickian syndrome” to describe obese and sleepy patients, in homage to Dickens’ character “Joe”. As early as 1956, Bickelmann et al [2] reported that the “Pickwickian syndrome” was associated with extreme obesity and alveolar hypoventilation.
Gastaut’s research group described three different types of apnea, namely, obstructive apnea central apnea, and mixed apnea. In 1973, Guilleminault introduced the apnea-hypopnea index (AHI), which refers to the total number of apnea and hypopnea episodes per hour of sleep, and proved, along with Dement, that obesity is not a prerequisite for OSA. In 1977, Guilleminault and Dement used the term “sleep apnea syndrome”, in association with hypertension and electrocardiographic pathologies. [3]
Recently, much research on OSA has been conducted with a view to help elucidate the characteristic features of OSA. Sleep is a process through which the body restores energy used during the day. Not much is known about its biological purpose, but its evaluation can be undertaken by muscle and brain electrical activity, and ocular movement. Good-quality sleep entails several functions; these include physical recovery, biochemical refreshment, memory consolidation and psychological well-being. [4]
In adults, sleep is regulated by a cycle of five periods. The first four periods belong to non-rapid eye movement sleep (light and deep stage) and the fifth period is named the rapid-eye-movement (REM) or paradoxical sleep (active stage). The progression from the first stage to the RAM constitutes one sleep cycle. Generally, there are four to six sleep cycles per night; during which activities of the brain, muscles, and the cardio-respiratory system fluctuate (Figure 2, 3). [4]
A sleep cycle (non-REM to REM stages). [
Consecutive wave of non REM to REM sleep cycles (I to IV). Throughout the night, REM becomes longer than slow wave sleep (stage 3and 4). MT: movement time, WT: wake time. [
During these sleep stages, several sleeping disorders can occur. International classification of Sleep Disorders (ICSD-3), revisited in 2014, includes the following broad categories: [5]
Insomnia
Sleep related-breathing disorders
hypersomnomlence Central disorders
Circadian rhythm sleep-wake disorders
Parasomnias
Sleep related-movement disorders
Sleep apnea is the most common sleep disorder related to breathing. There are 3 types of sleep apnea: Obstructive, central, and mixed (a combination of both forms). Obstructive sleep apnea (OSA) is caused by partial or complete obstruction at multiple levels of the upper airway, producing reduction (hypopnea), or cessation (apnea) of airflow. Due to the lack of adequate alveolar ventilation, oxygen saturation may drop and partial pressure of CO2 may occasionally increase. Snoring and sleep fragmentation are common with OSA that can be graded as mild, moderate and severe.[6] Adults and children are equally affected. However, the prevalence, etiology and pathophysiology of the disorder differ from one group to another. It is important to note that the physiopathology and etiology of OSA are poorly understood.
Furthermore, OSA is associated with neuropsychological impairment, sexual dysfunction, metabolic and cardiovascular co-morbidities; and causes an increase in mortality. Quality of life and economic potential are also affected: snoring affects the sleeping pattern of the partner, and frequent arousals at night result in relative sleep deprivation and can cause excessive daytime sleepiness, loss of concentration and motor vehicle accidents.[4]-[7] Therefore, OSA is regarded as a public health condition and increases the consumption of health care resources.
Continuous positive airway pressure (CPAP) is considered a golden standard treatment; oral appliances and surgical procedures for upper airway soft tissues and maxilla-mandibular advancement are other alternatives. Hence OSA treatment requires a multidisciplinary management. [8] Orthodontists, sleep specialists and surgeons should all be involved in managing and treating OSA. This chapter gives a comprehensive account of the literature on OSA and underlines the role of orthodontists in managing OSA with a view to improve the physical, mental and social status of patients diagnosed with OSA.
Due to various definitions of respiratory events and differences in study design, contradictory variable prevalence rates of OSA are reported. The American Academy of Sleep Medicine published the first guidelines to standardize the definition of OSA; however, the standardization of OSA definition only expanded the diagnostic criteria.[1] According to the Wisconsin sleep cohort study, the estimated prevalence of moderate to severe sleep breathing disorder in the United States for the period of 1988–2011 ranged from 3% to 17% in adults depending on sex and age; OSA seemed to affect especially middle-aged and elderly men and has increased substantially over the last two decades in the US. [9] In Morocco, however, OSA prevalence ranges from 5, 4% to 7, and 9% in the general population. [10] De Backer (2013) reported that epidemiological studies investigating the prevalence of OSA are all biased because there is a lack of a uniform definition. He also indicated that the prevalence of an AHI of >5 events per hour in the general population (without taking into account symptoms of sleepiness) has been estimated to be 24% in the male population. When symptoms of sleepiness are also taken into account, this prevalence goes down to 4% in males and 2% in females. [11]
In the literature on OSA, most researches agree that risk factors for OSA include obesity, upper airway and craniofacial abnormalities, gender, age, alcohol consumption and cigarette smoking. [12] Obesity, particularly central or upper body fat distribution, with increased neck circumference (collar size) is a main risk factor for OSA. But this association may be less important with the elderly. In non-obese patients, craniofacial abnormality like micrognathia and retrognathia may also be considered as a risk factor leading to OSA. [13]
Aging is also associated with higher OSA prevalence. Still, it is not clear if OSA in the elderly compared to middle-aged adults manifests itself the same way; middle age and over-weight adult men seem to have the highest prevalence of OSA. However, after menopause, prevalence seems to be the same for both women and men. [1]Some studies have examined craniofacial features among different ethnic groups; their objective was to investigate whether ethnicity differences had an effect on the prevalence of OSA. These studies reported an increased risk of OSA among African-Americans, Latinos and Asians. [14]-[17] Wong et al. (2005) claimed that the hyoid bone was located more caudally in Chinese subjects and may be a severity indicator in this population. [18] In addition, OSA prevalence seems to be much higher in patients with cardiac or metabolic disorders than in the general population. Other factors such as heredity, hormonal change, sedative hypnotics and supine sleep position have also been described as risk conditions for developing OSA. [11, 12]
Epidemiologic data have shown a strong association between untreated obstructive sleep apnea and incident cardio and cerebrovascular morbidity and mortality. [19, 20] These co-morbid conditions may be due, in part, to common risk factors (i.e. obesity and hypertension), and also to hypoxemia-hypercapnia, which can lead to vascular dysfunctions. [21] In an18-year mortality follow-up conducted on the population-based Wisconsin Sleep Cohort sample (n = 1522), Young et al. found a significant mortality risk with untreated sleep breathing disorder (SBD). They underscored the need for early diagnosis and treatment of SBD, indicated by frequent episodes of apnea and hypopnea, regardless of sleepiness symptoms.[20]A recent review of OSA in adults reported an increased risk of morbidity and mortality associated with OSA, which reached its peak at 55 years of age. [12], This association seems to disappear after 70 yrs. [22]Sampaio et al., 2012 suggested that women revealed more psychological morbidity associated with OSAS. Therefore, it seems extremely important to look at women as potential patients for sleep apnea. [23] However, Gozal and Kheirandish-Gozal highlighted the potential interaction between gene polymorphisms, organ vulnerability, and the phenotypic expression of OSA and suggested that it should be identified and incorporated into future prediction schemes of morbidity risks associated with OSA. [24]
In recent years, the understanding of the pathophysiology of sleep-breathing disorder has improved. Central nervous system regulation of breathing is now recognized as a significant contributor to the pathogenesis of OSA. To understand the pathophysiologic mechanisms that contribute to OSA, an overview of anatomical and physiological aspects of upper airway is in order.
The upper airway is a complex, multifunctional, and dynamic neuro-mechanical system. It is defined as the passageway for gas and food, beginning at the mouth and nose and ending at the epiglottis and vocal cords. It is composed of bony structures (maxilla, mandible and hyoid bone) and soft tissues (tonsils, soft palate, tongue, uvula, pharyngeal muscle, para-pharyngeal fat pads and lateral wall of the pharynx). The mandible and hyoid bone are the principal craniofacial bone structures that determine the dimensions of the upper airways. Soft tissues form the walls of the upper airways and they are supported by bone structures.[1, 25] The upper airways are typically divided into three segments: The nasopharynx (end of the nasal septum to the margin of the soft palate), the oropharynx (free margin of the soft palate to the tip of the epiglottis), divided into the retropalatal and retroglossal regions, and the hypopharynx (tip of the epiglottis to the vocal cords) (Figure 4).
Sagittal magnetic resonance imaging of airway and division of oropharynx. (Clete A. Kushida)
The pharynx has several functions that enter into competition with each other; it requires patency and closure.[1, 4] It serves the neurological (speech, taste, smell), but also gastro-intestinal and respiratory system (chewing, swallowing, breathing).Speech and swallowing require that the upper airway be collapsible. However, during breathing, the pharynx must remain patent.
Oropharynx and hypopharynx compose the collapsible portion of the pharynx. Due to the absence of bone and cartilage in these segments, their lumen patency, during awakening and sleep, depends heavily on muscle activity and intrinsic airway collapsibility, which is dictated by a combination of passive mechanical properties and active neural mechanisms.
During inspiration, negative intra-thoracic pressure is transmitted to the upper airways, resulting in a reduction in the transverse area of the pharynx. [25] The permeability of the upper airways is maintained through the balance between opposing forces from factors that collapse the airway and those that promote its patency. This is called “the balance of pressure concept” and involves the following determinants (Figure 5): [1,4, 26]
The baseline pharyngeal area, determined by both craniofacial and soft tissue structures;
The compliance or collapsibility of the airway;
The negative intraluminal pressure within the airway (intraluminal pressure), transmitted from inspiratory muscles (the diaphragm, the external intercostal muscles....), that tends to narrow the airway;
The pressure acting on the outside surface of the pharyngeal wall (tissue pressure), which also tends to collapse the airway such as compression by the lateral pharyngeal and submandibular fat pad and a large tongue confined to a small oral cavity;
The positive extra-luminal pressure from the abduction force of the pharyngeal dilator muscles, which is directed outwards, and functions to increase cross-sectional area.
Pharyngeal dilating muscles can be divided into four groups: [1, 4]
Muscles influencing hyoid bone position such as geniohyoid and sternohyoid
Muscles of tongue: Genioglossus is the largest and the most important muscle
Muscles of the palate such as tensor palatini and levator palatini
Muscles protruding the mandible, principally the pterygoid muscles
In normal individuals in awake state, the upper airway dimensions remain practically constant throughout inspiration by neuromotor mechanisms, like reflex muscle activation in response to stimuli such as sub-atmospheric pressure and hypercapnia. However, during sleep, neuromotor tone decreases and upper airway resistance increases considerably especially in sleep onset and REM stages. These physiologic variations are counteracted by a reduction of diaphragm and intercostal muscles activity and thus a decrease in inspiratory pressure. This tendency for the human upper airway to collapse predisposes it to abnormal deformation during sleep, mainly in susceptible individuals. [1,4, 27]
Determinants of upper airway caliber. PL = intraluminal pressure; Ptis = pressure in the tissues surrounding the pharyngeal wall; Pmusc = pressure exerted by the pharyngeal dilating muscles; V = change in volume; P = change in pressure. [
OSA results from a combination of structural upper airway narrowing and abnormal upper airway neuromotor tone. It is believed that the upper airways collapse more easily in OSA patients and occurs at slightly negative intra-thoracic pressures or even positive pressures. [27] Narrowing can occur in more than one site. The retropalatal or velopharyngeal region is the most common site; but the collapse usually extends to other locations. Since REM sleep is associated with greater muscle hypotonia compared to non-REM sleep, sleep-breathing disorder is more likely to occur during REM sleep. [13] In addition, the sleep-awake state in the pathogenesis of OSA is important to highlight. OSA patients, even with the most severe apnea, have generally no respiratory dysfunction during wakefulness through compensatory systems. [28]
According to recent studies on OSA pathophysiology, anatomical factors are not the whole story. The coordination between collapsing and dilating forces is an important concept and there is increasing evidence that the quantity and pattern of ventilation plays a substantial role in airway collapse [29] as well as the presence of upper airway neuropathology. [28] In addition, not all individuals with OSA have the same anatomical features. Thus, OSA pathophysiological factors are usually divided into three categories, whose complex interplay may explain the variable response to treatment:
Anatomic factors that effectively reduce airway caliber;
Non-anatomic factors that promote increased upper airway collapsibility and include: mechanical factors that are passive and related to tissues properties; and
neurological factors that change with the state of awakening or sleep
There have been a number of studies comparing anatomic features of OSA patients and normal individuals. Upper airway imaging techniques such as cephalometry, acoustic reflection, nasopharyngoscopy, computed tomography and magnetic resonance imaging, have greatly improved the understanding of OSA biomechanical aspect, and guided treatment modalities.
Over the past several decades, many studies have demonstrated that patients with OSA have significant craniofacial and upper airway abnormalities when compared with age matched and sex matched controls. [17, 30]
Typical abnormalities include retroposition of the mandible and maxilla, shorter mandibular body length, longer anterior facial height, steeper and shorter anterior cranial base.... [1, 4, 13, 17]
However recent studies have shown no strong evidence for a direct causal relationship between sagittal and vertical craniofacial features and sleep-breathing disorder. In contrast, transverse width in the maxilla has a real impact with strong support for a narrow maxilla in OSA patients. [31]-[32] In addition, there is theoretical evidence that the size and the shape of the upper airway are also important and influence upper airway collapsibility.[4, 13] Imaging studies have shown reduced nasopharyngeal and oropharyngeal sagittal dimensions in OSA cases, associated with longer soft palate and longer airway. Indeed, the upper airway long axis of OSA patients is likely to be oriented transversely compared to the wide, elliptically shaped airway of normal controls.[33]-[35]
Lung volume is also reported to influence upper airway caliber and compliance.[13, 29] Decreased lung volume results in a caudal traction effect, which decreases the pharynx area and increases its resistance and its collapsibility due to a loss of tracheal tug.
Nasal airway pressure required to maintain airway patency is defined as the critical closing pressure (Pcrit). [4] It has been demonstrated that Pcrit is related to anatomical features and lung volumes, and shown to correlate with soft palate length in obese patients and airway length and hyoid-mandibular distance in non-obese patients [13]
On the other hand, the magnitude of extra luminal tissue pressure depends on the interaction of the upper airway soft tissues and the bony compartment size (Figure 6).[36] According to this model, soft tissues excess like in obesity, or restriction in bony compartment size such as retrognathia or both can lead to tissue pressure increase, thereby reducing airway caliber and predisposing to OSA. Soft tissues excess can be seen in case of tongue, soft palate and pharyngeal wall volume augmentation; but also in adenoids and tonsils lymphoid tissue hypertrophy.
Despite the relationship between structural features and function, some patients with OSA do not have clear anatomic abnormalities. Evidence for a direct causal relationship between craniofacial structure and OSAs has yet to be elucidated because several methodological deficiencies in the literature and lack of research standardization methods and treatment success definitions have been highlighted.
This category includes all factors underlying collapsibility. They are divided into pure mechanic and neurologic factors. In OSA patients, airway dilation appears less coordinated than normal subjects and intrinsic mechanical properties of airway tissues are altered (Figure 7). [30, 37]
The respiratory control pattern generator responsible for automatic control ventilation is located into the brainstem. Respiratory rhythm is regulated by chemoreceptors and neural input from the upper airway and lungs to the brainstem neuronal network.[4] Instability of ventilatory control contributes to OSA pathophysiology by leading to periodic breathing and compromising airway patency during the ventilatory cycle. [28] It has also been suggested that upper airway inflammation and trauma caused by snoring and the hypoxia caused by intermittent upper airway collapse may impair the sensory pathways (upper airway mucosa) and the activation of neuromuscular reflexes (pharyngeal dilator muscles) rendering the upper airway prone to collapse. [38]
Schematic model proposed by Isono et al., 1997 [
Other factors that may contribute to OSA pathophysiology include head posture, vascular supply to the mucosa and tissues surrounding the airway and arousal threshold.
Strohl et al. (2012) [39] reported that changes in blood pressure and/or pharyngeal muscles vascularity could affect airway stability and patency. Mucosal blood flow may either help resist distortion or contribute to narrowing if engorged.
On the other hand, flexion and extension of the neck affect the mechanics of the upper airway because the axis of rotation for extension and flexion is behind the airway. Thus, altered sleep position, mainly supine, may increase upper airway collapsibility and predispose to OSA particularly in adults because of tongue base prolapse. [40] In contrast, OSA children breathe better in the supine than in the prone position; this may be true because obstruction in children occurs usually at the level of the adenoids or soft palate rather than at the level of the tongue [1]
Although arousal is known to reinstate ventilation and thus to be protective in OSA, it is not essential to terminate an obstructive event. Low arousal threshold can exacerbate instability and worsen OSA.[1, 41] However, some authors who believe, that poor sleep is a secondary cause of OSA have rejected this claim. [29]
OSA has been shown to aggregate significantly within families. Genetic factors are likely to determine upper airway anatomy, neuromuscular activity and ventilatory control stability; these factors produce the phenotype of the OSA syndrome.[1, 4, 25, 42].
In sum, it is probably reliable to conclude that, in OSA individuals, there is a multiplicity of coexisting factors interacting to varying degrees at night; and everyone has biological susceptibility and responds differently to environmental predisposing factors. Because OSA is a public health problem, its treatment should target the specific pathophysiologic processes that contribute to the collapse of the upper airway, in an attempt to alleviate symptoms and modify the long-term health consequences.
Aimed at maximal standardization and better care of patients, a task force of the American Academy of Sleep Medicine (AASM) has recommended terminology and standards of practice for recording sleep and breathing, and assigned evidence-based definitions for abnormal events, parameters and disorders. [43] These definitions are still valid today.
A clear decrease (> 50%) from baseline in the amplitude of a valid measure of breathing during sleep;
Or an amplitude reduction (< 50%) associated with either an oxyhemoglobin desaturation (> 3%) or an arousal. [4]
The exact magnitude of desaturation for a hypopnea varies in the literature. In routine clinical practice, it may not be necessary to differentiate apneas from hypopneas when both have similar pathophysiological consequences.[13] It is recommended to associate these two events in the form of an index of apnea / hypopneas (AHI).
This index, also termed respiratory disturbance index (RDI), refers to the total number of apnea and hypopnea episodes per hour of sleep. It is calculated by dividing the total number of apneas/hypopneas during a recording period by the total sleep time. AHI is usually employed to quantify OSA severity, but also to compare individual patient data with normative as well as pre-treatment and post-treatment values.
As noted previously, OSA is characterized by repeated partial or complete collapses of the upper airway during sleep, which precludes or reduces airway flow. It is associated with excessive daytime somnolence, sleep fragmentation and adverse sequelae attributable to frequent obstructive apneas or hypopneas during sleep. According to the AASM, OSA refers to an AHI ≥ 5 associated to one or both of these two criteria:
Excessive daytime sleepiness (EDS) not explained by other factors
Manifestation of at least two of following symptoms that should co-exist:
Daily severe snoring
Choking or suffocation during sleep
Fragmented and non-restorative sleep
Diurnal tiredness
Concentration difficulties
Nocturia
However, the presence of 15 or more obstructive respiratory events per hour of sleep in the absence of sleep related symptoms is enough proof for the diagnosis of OSA due to the greater association of this severity of obstruction with important consequences such as increased cardiovascular disease risk.[44] Two indicators must be taken into account for severity estimation of OSA: AHI and the importance of diurnal hyper-somnolence after exclusion of another cause of sleepiness. Patients in normal sleep have an AHI of 5 or less. Patients with mild sleep apnea have an AHI of 5 to 15, with moderate sleep apnea typically 15 to 30 events and severe apnea 30 or more events per hour.
Despite its high estimated prevalence, awareness of OSA remains insufficient in the community.[4] Health professionals, including orthodontists, should not disregard the risk factors of OSA and should detect and diagnose this disorder. OSA screening should be based on sleep-oriented history and physical examination in conjunction with objective tests. When diagnosed, OSA severity level must be determined for an effective treatment decision.[44]
According to the AASM, sleep history is sought to evaluate OSA symptoms and to determine patients who present high-risk levels. A sleep examination is directed at modifying the OSA probability based on the history, looking for associated or complicating disease, and excluding other potential causes for symptoms.
Clinical assessment must encompass all sleep and physical features of the patient that may provide helpful guidance for screening this condition such as:
EDS is caused by sleep fragmentation due to frequent arousals at night. It is still a very subjective symptom that overlaps significantly with other factors such as tiredness and lethargy. [4] Epidemiological studies estimate EDS prevalence at 8% to 30% in the general population. [45]Sleepiness may occur during “passive” conditions, such as watching television or, in severe forms, during “active” conditions, such as conversation or driving. Several instruments have been developed to measure EDS. Currently, the most useful instrument is the Epworth Sleepiness Scale.[46] This questionnaire provides sleep propensity measure and has good test–retest reliability. It should be described with regards to onset, situation, and chronicity of sleep problems (Figure 8). [45]Objective laboratory sleep tests, like multiple sleep latency test (MSLT) or maintenance of wakefulness test (MWT) are also used for EDS assessment, but their limits are principally related to their costs and duration.
The presence of snoring alone is a poor predictor of OSA. Thus, it must be correlated with other accompanying clinical features. Similarly, snoring absence does not exclude OSA. If severe, snoring can affect social relationship and become one of the main complaints of patients. Talking to the partner and family members can be very helpful; they can often report signs, such as apnea or falling asleep unintentionally (that the patient may be unaware of or deny). Therefore, patients can report awakening during choking episodes. But this is less common among females. OSA can also be associated with array of nocturnal and daytime symptoms that are not necessarily specific to this affection, but can complete its clinical pattern and give an idea about its impact on patients’ functionalities. One can cite poor sleep quality, morning headaches, impaired memory, failed concentration, nocturia, and depression....[4]
Obesity is the main predisposing factor for OSA. It is usually quantified by BMI (Body Mass Index). Increased BMI is closely correlated to OSA likelihood and severity. [4, 13] Additionally, central obesity (i.e. fat around the neck and waist), evaluated by neck circumference and hip-to-waist ratio, is simple clinical measurements that seem most predictive for SDB. There is no evidenced threshold value for these measurements, but a BMI ≥ 30 kg/m2 and a neck circumference >17 inches in men and >16 inches in women are habitually used as critical values.[4] Moreover, a study found that waist-hip ratio is the most reliable correlate of OSA in both sexes; while neck circumference is an independent risk factor for males. [48]To establish OSA diagnosis, obesity indicators alone are not sufficient and further diagnostic testing is needed. [26]
Clinical examination should include anatomical features of craniofacial and oropharyngeal structures as they can compromise airway patency. Particular attention should be paid to upper airway narrowing signs such as tonsillar hypertrophy especially in children, nasal obstruction, macroglossia with dental impressions at the edge of the tongue, elongated uvula or soft palate inflammation. [44, 45] Oropharyngeal crowding can be assessed using the modified Mallampati classification designed originally by anesthetists to grade intubation difficulty (Figure 9). [49]
Modified Mallampati classification of oropharyngeal visualization. Class I: Soft palate, tonsils, pillars, and uvula, are clearly visible. Class II: Soft palate, pillars, and uvula are visible. Class III: only part of soft palate and base of uvula are visible. Class IV: Soft palate is not visible at all. 49
Other conditions that should be searched for when examining potential OSA patients are skeletal abnormalities because they are high risk factors among either obese or non-obese individuals. Actually, retrognathia, micrognathia, maxilla deficiency with high arched/narrow hard palate, longer anterior facial height, cranial base abnormalities or inferior hyoid bone position should be evaluated as they may suggest the presence of OSA. Cephalometric radiographs enable health professionals to obtain quantitative measures of these features. [50]
A clinical examination should not ignore respiratory, cardiovascular, and neurologic systems. In this area, medication history must be taken into account especially with regard to drugs that are associated with OSA (Barbiturates, Benzodiazepines...), those that sedate and/or decrease respiratory drive (Antihistamines, Antispasmodics, Anxiolytics, Muscle relaxants...) and those that impair sleep onset or maintenance (Anticholesterol agents, Appetite suppressants, Benzodiazepines, Caffeine, Nicotine, Diuretics...). Furthermore, since hypertension is described as independently associated with OSA, blood pressure has been integrated into several clinical prediction rules for sleep apnea. [22, 44]
To establish OSA severity, objective testing is required. There are two accepted methods: laboratory polysomnography (PSG) and home testing with portable monitors (PM)
Polysomnography is the golden standard method for diagnosing OSA. It records sleep-breathing pattern and oxygen saturation overnight via a minimum of 12 channels of physiological signal such as electroencephalogram, electrocardiogram, electromyogram, oronasal airflow, electroocculogram, respiratory effort, body position and oxygen saturation. This examination provides AHI by monitoring apnea and hypopnea occurrence. Clinical interpretation of OSA severity is based, in addition to AHI, on factors like oxygen desaturation and sleep fragmentation degrees. In general, a single night PSG is sufficient to make an appropriate OSA diagnosis. However, some variability can be identified in recordings between the first and the second night of a PSG, a phenomenon known as the “first night effect”. This may be due to factors such as sleep position and alcohol [44, 51]
Unlike PSG that is expensive and labor intensive, PM is performed at home and thus offers greater convenience for patients. Nonetheless, this procedure has some limits related to the lack of supervision, which can affect its reliability, but also to the impossibility to detect other sleep disorders such central apnea or nocturnal epilepsy. The choice between PSG and PM should take into consideration resource limitations and pre-test clinical evaluation. Thus, PSG could be performed if PM is technically inadequate or fails to establish OSA patients with a high pre-test probability.[44]
Furthermore, numerous imaging modalities are available for 2D or 3D craniofacial and airway study. They have potential usefulness in understanding the pathogenesis of sleep- breathing disorder, and planning of treatment (adenoidectomy, orthognathic surgery), but their routine use in the evaluation and diagnosis of OSA is limited. All diagnosis components previously studied (clinical examination and diagnostic testing) should be discussed with patients to establish a program including risk factors, consequences, but also treatment options/outcomes of OSA in the context of disease severity and patients’ expectations.[44]
Therapeutic approach of OSA requires interdisciplinary communication among healthcare professionals and long-term management with a regular follow-up. Patient adherence to therapy, potential side effects and further stability of results must be continually monitored. On the other hand, outcomes assessment should be performed after all therapy has been undertaken. The criteria used to determine successful treatment of OSA varies widely. A task force of AASM have reported some indicators for assessment of treatment results; these include resolution of sleepiness, OSA specific quality of life measures, patient and spousal satisfaction, adherence to therapy, avoidance of factors worsening disease, obtaining an adequate amount of sleep, practicing proper sleep hygiene and weight loss for overweight/obese patients. Objectively, clinicians strive to achieve at least 50% reduction in the baseline AHI in addition to reduction in AHI to <5 events per hour or <10 events per hour. However, less stringent definitions can be adopted. Treatment modalities of OSA can be divided into surgical and non-surgical treatment to which adjunctive therapies can be associated. Less invasive treatment should be selected whenever possible. Also, patients must be advised about surgical success rates and complications, the availability of alternative options and their levels of effectiveness. [52, 53]
This category includes continuous positive airway pressure (CPAP), behavior modifications, and oral appliances.
First described by Sullivan in 1981, CPAP was to become the golden standard of moderate to severe OSA treatment. [54].It consists of delivering, during sleep, compressed air into the airway to keep it open, by positive pressure across the airway walls and pneumatic splinting effect. CPAP can be applied through oral, nasal or oro-nasal interface; and the optimal level of positive airway pressure is determined by full-night, attended in-laboratory PSG. Successful therapy with CPAP depends greatly on individual patient acceptance and compliance that can fall for numerous reasons including functioning noise, discomfort, feelings of claustrophobia, and skin irritation. Thus, CPAP prescription requires explanation of benefits and medical reasons for its use. Patients should also be informed about the function and maintenance of equipment. According to the American college of Physician (ACP), moderate quality evidence has showed that CPAP improves sleep measurement in patients with at least moderate OSA (AHI > 15events/h), and there are no data to determine which patients benefit most from specific treatment strategies. [55] However, OSA remains at present the preferred treatment for OSA, as it could effectively reduce AHI and arousal index scores, and increase the minimum oxygen saturation. Finally, if CPAP use fails, based on objective monitoring and symptom evaluation, more efforts should be implemented to improve PAP use or consider alternative therapies.
CPAP device requiring the use of mask interface, sealed tubing and flow generator providing airflow. [
Behavior strategy includes all practices that enhance life routines and hygiene. It involves weight loss (ideally to a BMI of 25 kg/m2 or less), positional therapy, and avoidance of smoking, alcohol and sedatives 3h before sleep. Weight loss has been shown to improve AHI in obese patients with OSA. It is recommended for all overweight OSA patients and should be combined with a primary treatment for OSA. Sleeping in the supine position can affect airway size and patency with a decrease in the area of the lateral dimension of upper airway. Positional therapy keeps the patient in a non-supine position by positioning device like alarm, pillow, back-pack or tennis ball is an effective secondary therapy or can be a supplement to primary therapies for OSA in patients who have a low AHI in the non-supine position. To ascertain treatment outcomes, indicators, such as self-reported compliance, objective position monitoring, are used. However, studies argue that CPAP is still superior to positional therapy in reducing the severity of sleep apnea and increasing the oxygen saturation level during sleep in patients with positional OSA. [50]-[57]
Pierre Robin was the first orthodontist to have used oral appliances (OAs) in the 1900s for glossoptosis. Since the 80s, these oral devices were used as a non-invasive treatment for OSA. This therapy has proven to be effective in reducing the apnea and hypopnea index, improving oxygen saturation during sleep, and reducing snoring. OAs are recommended as an alternative therapy to CPAP for mild to moderate OSA patients with CPAP adverse effects or for those who do not tolerate or adhere to CPAP or those who refuse surgery. They are also appropriate for patients with primary snoring, who do not respond to treatment with behavioral measures such as weight loss or sleep position change. [44, 50]-[58]
Both Mandibular advancement devices (MADs) and tongue-retaining devices were described (TRD). But MADs are the most commonly used and evaluated in the literature. Orthodontists must indicate the most appropriate design of MADs for each patient, depending on dental history and complete examination of the stomatognathic system (soft tissues, dental occlusion, masticatory muscles and the temporomandibular joint). MADs cover the upper and lower teeth and hold the mandible in an advanced position with respect to the resting position. The appliance is constructed, adjusted, and gradually titrated (advanced forward) over several weeks until the snoring and daytime sleepiness are reduced to an acceptable level, or the patient cannot tolerate further advancement. They are worn during sleep and they act by enlarging obstructed upper airway by moving the mandible and tongue anteriorly and then the activation of airway dilator muscles. Craniofacial changes induced by OA were evaluated using cephalometric analysis. Significant modifications were reported: Retroclination of the maxillary incisors, proclination of the mandibular incisors, increased lower facial height, and changes in molar relationship. Loss of edema, caused by snoring and repetitive apneas, associating OAs seems to result in palatal length decrease and pharyngeal area increase. OAs have some side effects: Dry mouth, excessive salivation, jaw discomfort, myofacial pain and tooth grinding. However, they are frequently reported as mild, acceptable, and transient. Another inconvenience of OAs is the time needed for titration, which makes it a second choice for severe or high symptomatic OSA treatment. [58]
The Academy of Dental Sleep Medicine suggested the use of cephalograms as a diagnostic aid at the initial dental examination of every patient receiving OA treatment. In addition, some cephalometric predictors like longer maxilla, shorter soft palate and decreased distance between mandibular plane and hyoid bone have been related to successful MAD treatment of OSA. [4]
A 27-year-old man with mild OSA: initial profile view (A), and initial occlusal views (B). We can note a severe retrognathia compensated with a class I dental occlusion.
A MAD device was indicated for night.
Lateral Cephalograms before (left) and after (right) oral appliance positioning showing change in hyoid bone position and slight enlargement of retroglossal area of pharynx
Surgical management was the first therapeutic modality employed to treat SDB by placement of a tracheotomy tube to bypass upper airway obstruction in Pickwickian patients. Currently, there are numerous surgical approaches to upper airway treatment in OSA, which consist of upper airway tissue reduction or reconstruction at different levels. OSA surgical management often involves several procedures that can be at times multi-phased or a combination of multi-level simultaneous surgeries. The selection of the most adequate surgery entails a meticulous preoperative multidisciplinary assessment and rests on the surgeon’s experience. [59]
OSA surgery should be determined after clinical diagnosis and severity assessment by objective testing. It is recommended for patients who are medically and psychologically able to tolerate the operation ; primary surgery is advocated in mild OSA and severe obstructing anatomy feasible to treat surgically such as tonsillar hypertrophy and nasal obstruction; surgery is recommended secondarily in cases of ineffective treatment or intolerance to the other non-invasive therapies in mild, moderate and severe OSA. Surgical treatment involves evaluation of three anatomic sections of the airway for detection of collapse-related abnormalities namely:
the nose (alar cartilage deformities, septal deviations, enlarged turbinates, nasal floor constriction),
the retropalatal area (lymphoid hyperplasia, retrusive maxilla, long palate) and
the retroglossal area and the tongue (mandibular retrognathia).
Thus, surgical procedures can be classified as intra-pharyngeal or skeletal. Intra-pharyngeal surgery includes all procedures directed towards soft tissues of upper airway, the most common being uvulopalatopharyngoplasty (UPPP). Hard tissues surgery includes maxillomandibular advancement (MMA) (Figures 14-16) and genioglossus advancement (GGA) (Figure 17)
Profile views of a 34-year-old man with severe OSA. A: before treatment, B: after OSA management including orthognathic surgery (mandibular advancement osteotomy)
lateral cephalograms showing posterior airway space enlargement Before treatment (left) and after surgical mandibular advancement (right)
PSG registration: before treatment (left) and after mandibular advancement and adenoidectomy (right).
Genioglossus advancement technique. (A): rectangular osteotomy is created in the anterior mandible. (B) : The genial tubercle and the attached genioglossus muscle are advanced anteriorly. The bony fragment is rotated 90° to overlap the inferior border of the mandible and secured to the mandible with a titanium screw. [
Powell et al. have created a two-phase directed protocol (Powell-Riley surgical protocol) for surgical treatment of upper airway obstruction at several levels in order to avoid unnecessary surgery. Phase I surgery is designed essentially to treat the upper airway soft tissue (nose, palate, and tongue base) without dental occlusion or facial skeleton modifications. Clinical response is assessed, after adequate healing, four to six months following surgery by PSG. Persistent OSA requires phase II surgery indications. Phase II surgery refers to maxilla-mandibular advancement osteotomy, which physically creates more space for the tongue, thus enlarging the posterior airway space. [59]
UPPP has been developed to alleviate isolated obstructing tissues of the soft palate, lateral pharyngeal walls, and tonsils. However, according to ACP, it does not reliably normalize AHI when treating moderate to severe OSA, as a sole procedure. Furthermore, with regards to MMA, there is a need for more understanding of the relative risks and benefits of MMA compared to other treatment modalities. CPAP or OAs should generally be suggested ahead of MMA if the patient is consenting. These recommendations do not corroborate with other findings having reported a success rate of 89% obtained by physically expanding the facial skeletal framework and increasing tissue tension, which decreases velopharyngeal and suprahyoid musculature collapsibility. [53, 61]
Complications of maxilla-mandibular advancement surgery have been reported, including side effects such as neurosensory deficit, infection, bleeding, or temporomandibular joint problems; but patients’ satisfaction is reported to be as high as 95%. Finally, long-term stability depends on the body mass index, the amount of skeletal advancement, and the skill and experience of the surgeon.[60, 61]
The palatal implant is a new treatment option for snoring that emerged in 2003. It is composed of polyethylene terephthalate, a biocompatible material, and inserted into the soft palate to reduce vibration and collapsibility by stiffening the soft palate, thus reducing palatal flutter and snoring. Additional stiffening of the palate is achieved by fibrosis and formation of capsule in response to the inflammatory reaction. Studies have showed that they may be effective in some patients with mild obstructive sleep apnea, who cannot tolerate or do not adhere to positive airway pressure therapy, or in whom oral appliances have been considered and found to be ineffective or undesirable. However, at the present time, it is difficult to predict if it will be a reliably effective intervention or not. [55, 59, 62]
A wide range of medication targeting OSA treatment has been explored in the literature. Except for hypothyroidism or acromegaly in which medication can improve AHI, there are no really effective pharmacotherapies for OSA. Topical nasal corticosteroids can be used in patients with OSA and concomitant rhinitis especially in children, and thus may be a useful adjunct to primary therapies for OSA. In addition, Modafinil, a psychostimulant, is recommended for the treatment of residual excessive daytime sleepiness despite effective PAP treatment and absence of other evident causes for their sleepiness. [44, 63]
A Cochrane review issued in 2013 showed insufficient evidence to recommend any systemic pharmacological treatment for OSA; drug therapy needs to be targeted depending on the presence or absence of obesity and the predominance of OSA in a particular sleep stage. The review also reported that among all drugs evaluated, Donepezil is the most promising for further research. [64]
Bariatric surgery consists of a variety of operative techniques performed to promote weight reduction such reducing gastric banding, gastric and jujenoileal bypass or gastroplasty. It is often recommended for treatment of morbid obesity, particularly when associated with other medical complications (BMI ≥ 35 kg/m2) or those with a BMI ≥ 35 kg/m2 when dietary efforts fail at weight control. Therefore women seem likely to be candidates for this method of weight loss. [44, 65]
As cited above, OSA is associated with numerous craniofacial abnormalities. Orthodontics improvement of dento-facial morphology may have a positive impact on OSA components. Orthodontic professionals should provide treatment for OSA patients as well as diagnose potential OSA patients. Medical history and clinical examination allows orthodontists to identify the risk factors of OSA or signs related to OSA (obesity, allergy, nasal dysfunction, maxillary constriction, retrognathia, long uvula, mouth breathing...) or record some symptoms reported by patients. Moreover, several imaging modalities (lateral and frontal cephalogram, cone beam computed tomography, MRI.) can assist Orthodontic professionals in assessment of this condition.
Orthodontic management of OSA syndrome could be provided to children as a preventive and interceptive modal or to adults by an interdisciplinary management. A significant number of children suffering from respiratory problems and obstructive sleep apnea have nasal obstruction associated with a narrow maxilla that may increase nasal resistance and alter the tongue posture, leading to a narrowing of the retroglossal airway and OSA. Maxillary expansion with orthopedic appliances is very effective in these cases allowing for an increase of nasal cavity dimension. It can be combined with adenotonsillectomy for best results in children with OSA associated with adenotonsillar hypertrophy. [4, 66, 67] Among adults, this expansion can be attained by RME or surgically assisted RME and has been reported to reduce snoring and hyper-somnolence.
Maxillomandibular advancement can also be provided either by surgery or orthopedic systems as therapeutic or preventive measure in OSA cases. A good finishing of dental occlusion is desirable. On the other hand, It has been suggested [68] that the improvement observed in the respiratory symptoms with surgical MMA, namely apnea/hypopnea episodes, should be correlated with SNA increase after surgery which may help maxillofacial surgeons establish selective criteria for the surgical approach to sleep apnea syndrome patients. Mandibular advancement in case of retrognathia can be accomplished by oral appliances in adulthood, functional appliance therapy in younger patients, mandibular distraction osteogenesis or osteotomies, and is among the most frequently used approaches in OSA management.
Orthodontists can also have a role in the treatment of OSA consequences especially those with nocturnal bruxism, which differs from stress-related bruxism. Sleep bruxism has been shown to be prevalent in children, and correlated with sleep disturbances (microarousals). It is characterized by rhythmic masticatory muscle activity and may be related to the patients’ attempt to improve airway patency during episodes of oxygen desaturation via co-activation of jaw opening and closing muscles. Its management requires use of night splints and restorative dentistry.
In brief, although the bi-directional cause and effect relationship between OSA and craniofacial abnormalities remains to be proven, early identification and treatment of dento-facial disorders may enhance OSA management with respect to preventive and curative approaches. Interdisciplinary professional communication is crucial for the success of global OSA management.
OSA is a common breathing disorder, which affects all age groups. It is a serious public health problem. Because of its potential pathophysiological consequences, it associates alteration of quality of life, decreased economic potential and increased morbidity and mortality in affected patients. Assessment of OSA requires a thorough clinical examination as well as overnight testing to determine PSA presence and severity before initiating treatment. Polysomnography remains the most common and reliable test for OSA diagnosis. Additionally, several imaging modalities can be used for upper airway structure and function during wakefulness and sleep. Treatment modalities of OSA are aimed at increasing life expectancy, decreasing disease problems and improving the quality of life. CPAP is still the mainstay for treatment of moderate to severe OSA. However, medical or surgical alternatives can be used in case of failure or non-compliance of the patients.
OSA is also a condition that orthodontists may encounter in their daily practice; thus, they are in a better position to diagnose and treat it using a multidisciplinary approach and management.
In recent years, the field of quantum computing [1] has developed into an active and diverse field of research, and significant progress has been made in a number of important areas. For a relatively small number of applications, quantum algorithms have been developed that provide a significant speedup relative to classical methods. Shor’s algorithm for factoring composite integers and Grover’s algorithm for quantum search were key developments in establishing quantum computing. More recently, significant progress has been made in the area of quantum chemistry and quantum physics. Beyond those two fields, only recently have quantum computing applications appeared in other areas of science and engineering, e.g., work in computational electromagnetics [2, 3], mixing in turbulent flow [4], and computational fluid dynamics [5]. More general applications have been developed which take advantage of the unique capabilities of quantum computing platforms, e.g., methods for the solution of linear systems of equations [6] and Poisson equation [7].
\nIn recent years significant progress has been made in designing and constructing quantum computers. Currently available quantum computers are relatively small-scale and have become known as noisy intermediate-scale quantum (NISQ) computers. These machines have a limited number of qubits (expected to increase to 50–100 in coming years), a limited connectivity between these qubits, a small set of available quantum gates, and typically very little or no quantum error correction.
\nThis chapter describes results of a recent investigation aiming to assess the potential of quantum computing and suitably designed algorithms for future computational fluid dynamics application, particularly for NISQ-type quantum hardware. In this work, the quantum circuit model is used for a “universal” or “digital” quantum computer, i.e., work on adiabatic quantum computing is not considered here. In the absence of the required quantum hardware, large-scale parallel simulations on parallel classical computers are required in developing such algorithms. In this work the recently developed quantum simulator [5] included in the MΦC multi-physics CFD framework is used [8, 9].
\nIn the near future, the most likely scenario for the introduction of quantum computing hardware is through the quantum coprocessor model, i.e., where a quantum processing unit (QPU) is loosely coupled to a classical computer with one or more CPUs [10]. In current designs, the quantum processor requires storage at low temperatures in a cryostat leading to a distinct physical separation between the classical and quantum hardware. Coupling takes place by exchanging classical information. In application of this hybrid quantum/classical approach, the quantum processor acts like a coprocessor with the quantum processor dealing with selected computationally demanding tasks. The quantum processor receives information from the CPU, and this is used to initialize the quantum state in the quantum processor. During the quantum simulation, the quantum state is transformed by application of quantum gates in quantum circuits. Then measurement operations are used to extract classical information from this quantum state, and this is subsequently passed to the CPU. Since in quantum mechanics a measurement leads to the (partial) collapse of the quantum state, in the hybrid classical/quantum approach, typically multiple realizations of the quantum state are needed to obtain classical information with acceptable levels of noise and uncertainty. It is important to recognize that, since initializing a particular quantum state in quantum computer can be a significant challenge, this hybrid approach can only be expected to lead to significant computational speedups in case the quantum simulation is significantly faster for the selected problem than conventional solution methods.
\nAs an example of this hybrid classical/quantum approach, the author introduced a quantum computing application in which the vortex-in-cell method was used to solve the incompressible-flow Navier-Stokes equations in a regular domain [5]. In this algorithm, the Poisson solvers dominating CPU time requirements are based on the quantum computing equivalent of the fast Fourier transform, i.e., the quantum Fourier transform. In this chapter, this algorithm and its application to example flow problems are investigated further. Specifically, the effect of applying an approximate QFT instead of the full QFT is analyzed for different levels of approximation or truncating of rotation gates in the quantum circuit implementation.
\nThe second part of this chapter describes a more recent investigation into the development of quantum algorithms relevant for computational aerodynamics based on modeling at the kinetic level. The key innovation in these developments is the design targeting execution of the algorithm fully on the quantum processor. In particular, at the start of the simulation, multiple quantum states in the quantum processor would be initialized. Then, the quantum algorithms would perform a series of unitary transformations. Only at the end of the simulation would measurements be performed to extract the required classical. A key question this study aims to answer is for which applications this approach is feasible.
\nThis chapter is organized as follows. Section 2 describes key principles of quantum computing relevant to the quantum algorithms for fluid simulations described here. Section 3 describes the hybrid quantum/classical implementation of the vortex-in-cell method along with a number of example applications. The quantum discrete-velocity algorithm for kinetic flow modeling is described in Section 4. Conclusions and future research directions are presented in Section 5.
\nThe fundamental unit of quantum computation is the qubit [1]. Whereas a classical bit is confined to existing in either the 0 or 1 state, a qubit can be in a state of superposition, i.e., it exists in both states simultaneously. Upon measuring the qubit, the quantum state collapses to either of these two states, and the qubit is no longer in a state of superposition. The state of a qubit is defined through a pair of complex numbers [1]. A collection of \n
In the present work, the quantum circuit model of quantum computing is used. In this case, the unitary operations on a quantum state allowed by quantum mechanics are represented by a series of quantum (logic) gates acting on the quantum state. A quantum logic gate is an elementary quantum computing device that performs a fixed unitary operation on selected qubits in a fixed period of time. Written in a matrix form, unitary means that the determinant of the transformation equals one.
\nThe quantum state |Ψ> for a register with \n
We will now describe how this quantum state can be used to represent the storage space required for the computational problems of interest here, representing discretized partially differential equations. As a first step, consider a function
However, it is important to stress that the quantum state vector only represents the likelihood that upon measurement the quantum state collapses into a particular state [1]. In other words, with \n
The ability to implement the quantum Fourier transform (QFT) efficiently on a quantum computer is of paramount importance for many quantum algorithms. Figure 1 shows the “standard” quantum circuit implementation of the QFT for an example register with 6 qubits. In Figure 1, “H” represents the one-qubit Hadamard gate, and the “Rk” gates are controlled rotation gates over an angle defined by index “k,” i.e., \n
Quantum circuit for QFT on six-qubit register.
A particular challenge is presented by the controlled rotation gates particularly those involving small angles. The QFT can be implemented approximately by removing all rotation gates with angles smaller than a certain threshold value, resulting in the approximate QFT (AQFT). In particular for fault-tolerant implementations, this is desirable as it greatly reduces the gate count. In the following, we define the approximation or “band-limiting” in the AQFT as follows. The rotation gates are eliminated above a limit value “k,” i.e., for an angle smaller than 2\n
The vortex-in-cell method is a well-studied hybrid particle-mesh method for incompressible flows and is particularly well suited for flows in regular domains such that efficient Poisson solvers can be used. In the present work, the Fourier analysis approach to solving the problem in a fully periodic domain is used, using the QFT for the required discrete Fourier transforms.
\nThe vortex-in-cell (VIC) method solves the incompressible-flow Navier-Stokes equations, transformed into the Helmholtz equations for vorticity evolution [5]:
\nIn simulations using the VIC, the flow evolves through a (large) number of time steps. During each of these time steps, the velocity field is recomputed using solutions of three Poisson problems for stream function \n
This part of the VIC is of particular interest here, as it represents the part that would be performed by the quantum processor in the quantum coprocessor model.
\nFigure 2 shows an example of a VIC simulation of two leapfrogging vortex rings, i.e., flow structures of fundamental importance in fluid mechanics. The lower vortex ring is stronger than the ring above it, and it will therefore convect upward faster, leading to the interaction of the vortex rings as shown. The iso-surface represents vorticity strength, i.e., a direct indicator of the “strength” of the considered vortex. Results are compared for two different meshes, 1283 and 2563, to highlight the dependency of the solution on the chosen mesh size. Also, in the shown simulation, no quantum errors were simulated, and the full QFT was used. If we now replace the QFT with the AQFT, the results shown in Figures 3 and 4 are obtained. In Figure 3, the “k” limit in the QFT is set to five for both meshes, showing that for the finer mesh this leads to unacceptable errors, while the coarser-mesh simulation still produces worthwhile results. If the “k” limit for the finer mesh is increased from 5 to 6, i.e., more controlled rotation gates are included in the AQFT circuit, the simulation on the finer mesh can also be made to produce similarly useful results. These example results show what level of approximation in the QFT is tolerable for application of the VIC method. For other QFT-based CFD solvers, a similar sensitivity study would need to be conducted.
\nVortex-in-cell simulation of leapfrogging vortex rings. Effect of mesh refinement is shown. “Noiseless” simulation using full QFT.
Vortex-in-cell simulation of leapfrogging vortex rings. For two different mesh resolutions, the effect of applying AQFT is shown (“k” limit is 5).
Vortex-in-cell simulation of leapfrogging vortex rings. For 1283 mesh, AQFT (“k” limit 5) is used. For 2563 mesh, “k” limit in AQFT is 6.
In computational fluid dynamics, the most widely used methods involve solving the Navier-Stokes equations for a continuum fluid, i.e., where fluid density, velocity components, and energy in each location in the computational domain are to be found from conservation equations. The vortex-in-cell method used in the previous section employs the Navier-Stokes equations in a transformed form involving vorticity rather than velocity, but importantly it still uses the continuum flow assumption.
\nAn alternative approach to the Navier-Stokes-based modeling is a description of the flow at a more detailed level, i.e., at the kinetic level [11]. Instead of governing equations for mass, momentum, and energy conservation, the flow is now described by the Boltzmann equation governing a particle distribution function in state space (or 3D velocity space for a 3D monatomic gas flow) for each location in the considered domain [10].
\nFor a monatomic gas, the distribution function \n
The distribution function defines for each point \n
The key advantage of this approach is that non-continuum flows, i.e., flows for which the density is so low that we cannot assume it to act as a continuum, can also be modeled. However, the main problem is the large computational cost when using a direct discretization approach due to the high dimensionality, i.e., for a 3D flow problem, we have a six-dimensional solution space (or seven when including time).
\nA further main challenge is the cost of evaluating the collision term. For the free-molecular flows considered here, the collision term can be discarded, and we will use the
In the discrete-velocity method used here, the velocity space is discretized using a uniformly spaced Cartesian mesh. A maximum molecular velocity magnitude is defined, \n
The discrete-velocity approach used here has a number of characteristics facilitating a quantum implementation:
A uniformly spaced Cartesian mesh is used for the spatial discretization as well as for the discretization of the velocity space.
In case solid objects are present in the computational domain, these are rectangular, and its edges align with the mesh lines in the mesh. Specifically, solid bodies can be defined by “tagging” selected groups of cells in the mesh.
A constant velocity-space discretization is used in each point in space, i.e., the velocity-space boundaries defined earlier as well as the number of discrete velocities are identical in each cell.
The convection part of the Boltzmann equation (i.e., the second term on the left-hand side in the shown equation) along with gas-solid interactions determines the time evolution of the distribution function in the absence of interparticle collisions.
The time-integration method used here is based on the reservoir technique [13], such that during the time integration the convection step always exactly involves the distribution function defined in a cell of computational mesh to move to a cell that is a nearest neighbor. This is commonly referred to as “streaming” of data.
In the examples shown, problems are restricted to two-dimensional flows. For this case, the collisionless Boltzmann equation originally defined for 3D can be reduced to two kinetic equations for two reduced distribution functions:
\nwhere the velocity and coordinate vectors are now defined in 2D.
\nInspired by the previous work on the Dirac equation [14], an efficient quantum circuit implementation of the streaming operations in x- and y-direction on a Cartesian 2D mesh can be created as shown in Figure 5. The example shows how a 12-qubit register is used for a discretized function with 6 qubits defining the indices of 64 grid points in x- and y-coordinate directions. The circuits with the filled circles define streaming to “right” neighbors, i.e., when each control qubits has the |1> state, the target qubit gets negated (“X” symbol used here). Similarly, the left streaming operation employs multiple-control NOT gates with target qubits being negated when each control qubit is in state |0>.
\nQuantum circuit implementation of “left streaming” and “right streaming” in x- and y-direction on a 64 × 64 Cartesian mesh.
For the streaming operations in quantum discrete-velocity method, further extensions are needed. First, the quantum register needs to be extended relative to that shown in Figure 5 to account for the storage of two discretized reduced distributions defined in the discretized velocity space. The additional distribution function is accounted for using an additional qubit termed “g” in the following quantum circuit diagrams. The number of additional qubits needed for the discrete-velocity mesh clearly depends on the number of discrete velocities used. For example, for a 16 × 16 discrete-velocity mesh, we add 8 qubits (four for each direction in state space). The qubits are denoted by the “u0,”…, “v0,”… qubits in the quantum circuits. Finally, to account for solid objects, we use an additional qubit (“BC” in the diagrams) set to |1> to denote a cell within fluid and |0> for a cell within a solid. For a 64 × 64 Cartesian mesh and a 16 × 16 discrete-velocity mesh, Figure 6 shows the quantum circuit used to simulate the free-molecular flow around a rectangular body, for which the evolution of the flow field starting from an initial uniform flow is shown in Figure 7. The key feature in the quantum circuits shown in Figure 6 is the extended number of control qubits, i.e., beyond the checks on the qubits corresponding to spatial coordinates, control qubits also involve the “BC” qubit (fluid/solid flag) as well as the qubits related to the discrete-velocity indices. This least feature originates from the need to stream only data associated with selected discrete velocities in the used time-integration method.
\nQuantum circuit implementation of streaming operations for discrete-velocity method (with 16 × 16 velocity mesh). Two-dimensional domain with 64 × 64 Cartesian mesh.
Discrete-velocity simulation of Mach 2 flow around rectangular body. 64 × 64 Cartesian mesh, velocity-space mesh with 64 × 64 discrete velocities.
A key aspect of the flows simulated by the quantum algorithm described here are gas-solid interactions. In this work, specular-reflection boundary conditions are assumed. This means that upon hitting a solid surface, a gas particle will bounce off this surface with the wall-normal velocity component effectively getting reversed and the tangential-flow component being preserved. In Figure 7, the time evolution of a Mach 2 free-molecular flow is shown, starting from an initial flow at uniform velocity everywhere.
\nAs can be seen in Figure 7, the specular-reflection boundary conditions gradually make the velocity vectors align with the solid wall such that there is no longer a flow into the solid body. This is the physically correct behavior. In the quantum register, the indexing for the velocity-mesh data is designed such that a change of the sign of the discrete velocity implies a bit negation of qubits representing the index of the considered discrete velocity. As an example, Figure 8 shows the quantum circuit implementation of the specular reflection for a rectangular body. In this case, only 16 × 16 discrete velocities are used for clarity. It can be seen that control qubits are used to “select” cells in space for which to apply the boundary condition. A further control qubit involves the “BC” qubit representing the solid/fluid flag. The negation operation (“X”) is applied to the qubits representing the velocity-mesh index to create the “change of sign” of the considered discrete-velocity data. This circuit is shown as an illustration of the quantum algorithm design approach used here.
\nQuantum circuit implementation of specular-reflection boundary conditions for rectangular body. 64 × 64 Cartesian mesh, 16 × 16 discrete-velocity mesh.
Although the circuits shown in Figure 6 perform the correct convection operations, an important practical constraint needs to be considered. For the quantum computer implementations achieved so far and those foreseen for the near future, the kind of multi-qubit-controlled NOT operations used here cannot be implemented. A small set of native gates will be available which most likely includes NOT, CNOT, and the Toffoli gate.
\nThe solution around this limitation is the introduction of ancilla qubits, which can be regarded as the quantum equivalence of additional workspace in the memory of a classical computer. Then circuits involving multi-qubit operations involving a large number of control gates can be transformed into circuits with more qubits and a larger number of gate operations, however now with a smaller number of control qubits. As is typical in this context, we assume that the ancilla qubits are initially in |0>, and since these are to be reused multiple times, the transformed circuits need to reset the ancilla qubits of this state at the end of the operations. For the quantum circuits implementing streaming in positive
Quantum circuit implementation of streaming operation. Circuit transformations are shown for addition of 1, 2, and 3 ancilla qubits.
This chapter presented two different quantum algorithms with possible applications in computational fluid dynamics. Beyond their very different areas of application, the key differences are the computational model with regard the quantum coprocessor model of quantum computing. The hybrid quantum/classical algorithm for the vortex-in-cell method involves repeated exchanges of information between classical and quantum hardware, i.e., at each time step in the time integration. In contrast, the quantum algorithm implementing a discrete-velocity method for kinetic flow modeling can be performed on the quantum processor for the duration of the simulation, with classical information exchange only required at the start and end of the simulation.
\nThis work addressed a number of key challenges that remain to be investigated further. Firstly, the need for further efficient quantum algorithms as well as a further understanding of how to apply the quantum coprocessor model for this type of flow simulations was investigated. Secondly, the measurement-based extraction of classical information fundamentally changes the way quantum algorithms for CFD application will most likely be used. Finally, obtaining detailed information on the full flow field will be a challenge, so applications for which only certain characteristics of the solution are desired would present a good choice for future applications.
\nA part of the simulation results presented were obtained using the EPSRC-funded ARCHIE-WeSt High Performance Computer (www.archie-west.ac.uk), EPSRC grant no. EP/K000586/1.
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The scope of this chapter includes the taxonomy of time-series data clustering and the clustering of gene expression data as a case study.",book:{id:"9961",slug:"data-mining-methods-applications-and-systems",title:"Data Mining",fullTitle:"Data Mining - Methods, Applications and Systems"},signatures:"Esma Ergüner Özkoç",authors:[{id:"262719",title:"Dr.",name:"Esma",middleName:null,surname:"Ergüner Özkoç",slug:"esma-erguner-ozkoc",fullName:"Esma Ergüner Özkoç"}]}],onlineFirstChaptersFilter:{topicId:"87",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82302",title:"Collaborative XR Systems and Computer Games Development",slug:"collaborative-xr-systems-and-computer-games-development",totalDownloads:5,totalDimensionsCites:0,doi:"10.5772/intechopen.105555",abstract:"Computer games and, of course, the development associated with them have been in the spotlight for many years; recently, also with technologies, such as virtual reality or extended reality. The main part of this chapter presents the classification of collaborative XR systems, the concept of the major application architectures and the consistency models of shared virtual game environments. The next subchapter briefly deals with the sharing of property ownership. The mentioned concepts and examples used in the chapter are implemented in many works and projects using a collaborative environment (also in gamified form) developed in the laboratory LIRKIS, the home laboratory of the authors. The knowledge presented in this chapter may provide tips and inspiration for some other game projects, and practical and useful notes on the advantages or disadvantages of some systems will be interesting and useful.",book:{id:"11192",title:"Computer Game Development",coverURL:"https://cdn.intechopen.com/books/images_new/11192.jpg"},signatures:"Branislav Sobota, Marián Hudák and Emília Pietriková"},{id:"82031",title:"Serious Games Development and Impact for Business Education",slug:"serious-games-development-and-impact-for-business-education",totalDownloads:18,totalDimensionsCites:0,doi:"10.5772/intechopen.103085",abstract:"Learning methodologies and experiences have changed over the recent years thanks to the incorporation of digital technology, among many of these technologies are Serious Games, that has a better opportunity to be used during recent pandemic times, the process of designing and incorporating games technologies is not easy and there are very few available development tools, this paper focus on basic guidelines and a practical experience. 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There is a need to train teachers and create pedagogical departments that will enhance and develop this experiential learning tools.",book:{id:"11192",title:"Computer Game Development",coverURL:"https://cdn.intechopen.com/books/images_new/11192.jpg"},signatures:"Dario Liberona, Aravind Kumaresan, Lionel Valenzuela and Giovanny Tarazona"},{id:"81629",title:"Leveraging on Data Sciences: Review of Architectural Practice and Education in Nigeria",slug:"leveraging-on-data-sciences-review-of-architectural-practice-and-education-in-nigeria",totalDownloads:23,totalDimensionsCites:0,doi:"10.5772/intechopen.103097",abstract:"Big data sciences demand the significant role of the architect. Particularly, facilitate the birth of an antifragile construction industry and more robust data sciences community of professionals. Skilled community necessary to build sustainable liveable cities with emerging creator’s economy. Liveability, well-being, and sense of belonging in the city are connected. Conversely, dismissive attitude by decision-makers towards architectural practice and education, even among architects, in recognizing architecture as data-driven and source of data deserve rethink. Here the chapter demonstrates architects as data scientists and the symbiotic relationship that exist between architecture and 3D computer graphics while highlighting emerging data sciences opportunities and threats. The chapter adopted principally reviews of scholarly literatures, draws from authors’ 20-years personal experiences, and industry leaders’ views. The language is accessible yet academically concise. The chapter concluded with recommendations, including highlights of big data technologies potential transformation of 3D computer graphics. 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It was also possible to show that serious games can be very effective in teaching CPR.",book:{id:"11192",title:"Computer Game Development",coverURL:"https://cdn.intechopen.com/books/images_new/11192.jpg"},signatures:"Ingrid Nery Mendes, Maicon de Araújo Nogueira, Filipe Valente Mendes, Otavio Noura Teixeira and Viviane Almeida dos Santos"},{id:"80515",title:"View Synthesis Tool for VR Immersive Video",slug:"view-synthesis-tool-for-vr-immersive-video",totalDownloads:141,totalDimensionsCites:0,doi:"10.5772/intechopen.102382",abstract:"This chapter addresses the view synthesis of natural scenes in virtual reality (VR) using depth image-based rendering (DIBR). This method reaches photorealistic results as it directly warps photos to obtain the output, avoiding the need to photograph every possible viewpoint or to make a 3D reconstruction of a scene followed by a ray-tracing rendering. An overview of the DIBR approach and frequently encountered challenges (disocclusion and ghosting artifacts, multi-view blending, handling of non-Lambertian objects) are described. Such technology finds applications in VR immersive displays and holography. Finally, a comprehensive manual of the Reference View Synthesis software (RVS), an open-source tool tested on open datasets and recognized by the MPEG-I standardization activities (where “I” refers to “immersive”) is described for hands-on practicing.",book:{id:"11192",title:"Computer Game Development",coverURL:"https://cdn.intechopen.com/books/images_new/11192.jpg"},signatures:"Sarah Fachada, Daniele Bonatto, Mehrdad Teratani and Gauthier Lafruit"}],onlineFirstChaptersTotal:8},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:139,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:122,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,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:21,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. 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Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. 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He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. 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He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. 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Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. 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She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. 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Biosensors, Biomaterials and Tissue Engineering",value:9,count:1},{group:"subseries",caption:"Bioinspired Technology and Biomechanics",value:8,count:2},{group:"subseries",caption:"Bioinformatics and Medical Informatics",value:7,count:9}],publicationYearFilters:[{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2019",value:2019,count:5},{group:"publicationYear",caption:"2018",value:2018,count:3}],authors:{paginationCount:250,paginationItems:[{id:"274452",title:"Dr.",name:"Yousif",middleName:"Mohamed",surname:"Abdallah",slug:"yousif-abdallah",fullName:"Yousif Abdallah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274452/images/8324_n.jpg",biography:"I certainly enjoyed my experience in Radiotherapy and Nuclear Medicine, particularly it has been in different institutions and hospitals with different Medical Cultures and allocated resources. 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:{name:"University of Silesia",country:{name:"Poland"}}},{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:"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:{name:"Medical University Plovdiv",country:{name:"Bulgaria"}}},{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:"243698",title:"Dr.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:null,institution:null},{id:"7227",title:"Dr.",name:"Hiroaki",middleName:null,surname:"Matsui",slug:"hiroaki-matsui",fullName:"Hiroaki Matsui",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Tokyo",country:{name:"Japan"}}},{id:"312999",title:"Dr.",name:"Bernard O.",middleName:null,surname:"Asimeng",slug:"bernard-o.-asimeng",fullName:"Bernard O. Asimeng",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{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"}}}]}},subseries:{item:{id:"10",type:"subseries",title:"Animal Physiology",keywords:"Physiology, Comparative, Evolution, Biomolecules, Organ, Homeostasis, Anatomy, Pathology, Medical, Cell Division, Cell Signaling, Cell Growth, Cell Metabolism, Endocrine, Neuroscience, Cardiovascular, Development, Aging, Development",scope:"Physiology, the scientific study of functions and mechanisms of living systems, is an essential area of research in its own right, but also in relation to medicine and health sciences. The scope of this topic will range from molecular, biochemical, cellular, and physiological processes in all animal species. Work pertaining to the whole organism, organ systems, individual organs and tissues, cells, and biomolecules will be included. Medical, animal, cell, and comparative physiology and allied fields such as anatomy, histology, and pathology with physiology links will be covered in this topic. 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