\r\n\tMany tried to define it, and its definition is always related to those who are in power, that being explained by the fact that this power and the abuse of it precisely, gives the access to being corrupted and practicing the acts that fall under corruption.
\r\n\r\n\tWe can find various types of corruption such as bribery, lobbying, extortion, cronyism, nepotism, parochialism, patronage, influence peddling, graft, and embezzlement. Also giving or accepting bribes or inappropriate gifts, double-dealing, under-the-table transactions, manipulating elections, diverting funds, laundering money, and defrauding investors.
\r\n\tNo government is immune to corruption. According to the World Bank, “the causes of corruption are always contextual, rooted in a country's policies, bureaucratic traditions, political development, and social history”.
\r\n\tThis indeed has consequences for increasing inequality, impacts government expenditure and services, shadow economy, and crime.
\r\n\tThis book will be a collection of chapters on Corruption. It welcomes contributions related to the nature of corruption its types and how corruption is undertaken in a certain context and the ways to deal with corruption will be part of this book. We value including materials on Corruption in organizations and ways to solve it. The origins of corruption and the way to deal with corruption, how to provide solutions, and any new insights on corruption will be part of this book.
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For the first time, SS-like clinical condition was described by Mikulicz in 1892 [1]. However, the disease was fully described (clinically and histopathology) later by the Swedish ophthalmologist Henrik Sjögren in 1930. He detected coincidence of rheumatism and hyposecretion of lacrimal and salivary glands and introduced the new term
SS affects the exocrine glands; lymphocytic infiltration leads to sicca syndrome of the eyes, oral cavity, pharynx, larynx, and/or vagina [1, 3, 4, 5, 6]. Systemic manifestations of SS are divided into visceral (lung, heart, kidney, endocrine, nervous system, gastrointestinal) and non-visceral (skin, myalgia, arthralgia). The risk of lymphoma is higher in patients with SS than in general population [1, 4, 6, 7, 8]. SS can be primary-pSS (without any other accompanying symptoms) or secondary-sSS (with other autoimmune diseases: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), polyarteritis nodosa, systemic sclerosis, granulomatosis with polyangiitis (GPA), primary biliary cholangitis (PBC), mixed connective tissue disease, occult thyroid eye disease) [1, 3, 4, 5, 6, 9, 10, 11].
\nDry eye disease (DED) problems are involved in diagnostic criteria of SS as an important part of diagnosis. Patients with DED seek medical help for many years prior to SS diagnosis—about 25% of DED patients have an underlying rheumatic condition, commonly pSS. Only one-third of patients with SS carried final diagnosis prior to ocular symptoms [1, 11, 12]. Some studies demonstrated coincidence of DED and SS in 46.7% cases [1, 11].
\nPrimary Sjögren’s syndrome is a multifactorial disorder including genetic predisposition, hormonal, and environmental factors [6, 13]. The pathogenesis of SS is incompletely understood. For years, it has been considered as T-cell dependent autoimmune response; now, the role of B cells is also described and is known as important. Tissue destruction is associated with the infiltration by both activated T and autoreactive B cells [1, 4, 6].
\nPlasmacytoid dendritic cells produce interferon (IFN)-I responsible for apoptosis/necrosis of glandular epithelial cells—it upregulates the major histocompatibility complex (MHC) molecules (class I and II) and costimulatory molecules (CD80,CD86), promotes production of cytokines (interleukin IL-6, IL-10, IL-12, IL-15, IF-γ, tissue growth factor TGF-β, tumor necrosis factor TNF-α), and chemokines (CXCL-11, CXCL-12, CXCL-13, CXCL-21) responsible for leukocytes migration resulting activation of the inflammatory reaction [1, 4, 6, 14, 15].
\nGlandular epithelial cells’ necrosis/apoptosis reveals Sjögren-specific antibodies A (SSA, anti-RO) and B (SSB, anti-La)—though the role of these autoantigens is not completely clear, but the presence of them is one of the diagnostic criteria of pSS [1, 4]. Moreover, the presence of macrophage-derived chemokine (MDC) and thymus-activation-regulated chemokine (TARC), abnormal distribution of aquaporin (AQP)-5 cell membrane transporter, and defect in AQP-5 trafficking increased B-cell-activating factor (BAFF) and the matrix metalloproteinases (MMP) level were described in relationship with tissue damage in pSS [1, 4, 15, 16, 17].
\nAutoantibodies against type-3 muscarinic acetylcholine receptors are the suggested reason of peripheral neuropathies (PN) associated with SS though it has not been proved yet [6, 18].
\nTo standardize the diagnosis in patients taking part in clinical studies, to analyze results, and to facilitate the comparison of patients between centers, the classification criteria should be established.
\nIn 1993, the Preliminary European Classification criteria for SS were published, and for almost 10 years have been the base for clinical, observational, and interventional studies [6, 19]. In 2002, the American-European Consensus Group (AECG) published a revised version of the SS classification criteria [6, 20, 21, 22]. All documents include ocular disturbances. AECG criteria for DED consist of symptoms and signs. Positive response to one question: (1) Have you had daily, persistent, troublesome dry eyes for >3 months? (2) Do you have a recurrent sensation of sand or gravel in the eyes? (3) Do you use tear substitutes >3 times a day? or positive one of tests: Schirmer without anesthesia ≤ 5 mm/5 min or vital dye staining of the ocular surface (≥4 van Bijsterveld or Ocular Staining Score OSS ≥ 5, [19, 20, 21, 22, 23]).
\nBecause of their restrictive nature, the American College of Rheumatology approved the Sjögren’s International Collaborative Clinical Alliance (SICCA) approach in 2012. To diagnose SS with ACR/SICCA criteria at least 2 of 3 are necessary: (1) a positive serum anti-Ro/-SSA or/and anti-La/SSB or [positive rheumatoid factor RF and antinuclear antibody (ANA) ≥ 1:320], (2) focal lymphocytic sialadenitis defined as focus score ≥ 1 focus/4 mm2 in labial salivary gland biopsy samples, (3) OSS ≥ 3 [6, 21, 23].
\nMain differences between ACR/SICCA and AECG criteria are: (1) no subjective ocular and buccal symptoms and morphological or functional tests for salivary glands, (2) new OSS proposed by SICCA as the only test for ocular problems, (3) the association of RF positivity and ANA titer 1:320 as equivalent to anti-SSA/-SSB positivity [6, 21].
\nIn 2016, ACR and EULAR published new pSS criteria containing again the Schirmer test and OSS in the dry eye assessment, as well as the test of unstimulated saliva production as a measuring tool for dryness in the mouth. The assessment of minor salivary gland biopsies and confirmation of the presence of the SS-A/Ro antibody were of particular importance. The remaining autoantibodies were not considered to be peculiar enough to diagnose pSS [21].
\nThe main ocular manifestation of SS is DED. It is mainly a result of impaired lacrimal gland function due to inflammatory tissue damage. Hyposecretion of tears leads to aqueous-deficient DED. Moreover, exocrine glands of conjunctiva are also affected in SS and in connection with goblet cells reduction reveal evaporative DED [1, 6, 9, 22]. Ocular surface inflammation with conjunctival hyperemia and corneal epithelial damage leads to functional vision impairment [1, 2, 6, 22, 24]. Squamous metaplasia of the ocular surface epithelium, follicular conjunctivitis, corneal epitheliopathy, filamentary keratitis, sterile infiltrates, scleritis, poor epithelial integrity, recurrent erosions, dysesthesia, corneal ulceration, vascularization, opacification, and sometimes perforation were also described in SS patients [1, 2, 6, 22, 25].
\nDry eye disease among other diseases is the symptom causing the greatest morbidity and impairment of quality of life. Therefore, the patient is actively seeking a medical help. DED is typically diagnosed by evaluation of both eye symptoms and results of eye examination that symptoms not always match signs. Some patients have no symptoms though they have changes of ocular surface and others have significant eye discomfort, but there are very little signs in eye examination [1, 2, 22, 26, 27, 28].
\nThree characteristics features define DED: symptoms of discomfort, visual disturbance, and tear film instability with potential damage of ocular surface [9, 22, 28]. The discomfort is described as itching, stinging, burning, “foreign body sensation,” or, occasionally pain. Visual disturbance means fluctuation of vision, especially during reading or working at a computer. In those cases, blinking recovers the vision [22, 28].
\nThere are several questionnaires for the assessment of DED symptoms: Ocular Surface Disease Index (OSDI), the McMonnies questionnaire, the Impact of Dry Eye on Everyday Life survey (IDEEL), the Symptom Assessment in Dry Eye survey (SANDE), and the Standard Patient Evaluation of Eye Dryness questionnaire (SPEED). They are used as screening tests for DED, to diagnose DED, to monitor changes over time, and to control effect of the therapy in both clinical practice and research [6, 22, 23, 28]. Schaumberg et al. proposed a short questionnaire for clinical DED screening. It consists of only three questions: (1) Have you ever been diagnosed by a clinician as having dry eye syndrome? (2) How often do your eyes feel dry/not wet enough? and (3) How often do your eyes feel irritated? [28, 29, 30]. It has turned out that 2 specific symptoms quarried (dryness and irritation) are equivalent to asking up to 16 symptom questions [28, 31].
\nEvaluation of DED considers on: tear function, tear composition, and ocular surface changes.
\nThe biomicroscopic examination evaluates luster and integrity of the tear film, the marginal tear strip, debris, and inflammatory cells in the tear film. The marginal tear strip is normally 1 mm in height and in DED is reduced. In clinical practice, a tear meniscus below 0.2 mm is regarded as pathological [2, 6, 9, 22, 25, 28, 32]. It is observed with the wide beam of the light and measured with narrow beam or optical instruments (description of those instruments and the interpretation of their measurements are available on the Tear Film and Ocular Surface Society website; www.tearfilm.org) [9, 28]. Corneal filaments are responsible for uncomfortable or painful sensation of patients [28] Figure 1—(1).
\nCommon diagnostic tests for dry eye disease: (1) tear film meniscus; (2) Schirmer test; (3) fluorescein break-up time; (4) fluorescein staining; and (5) lissamine green staining.
Tear film instability is produced by either aqueous-deficient or evaporative or a combination of both mechanisms of DED. It can be also effect of ocular surface irregularities. To determine tear film stability tear film break-up time (TBUT) is used. The fluorescein dye is placed into the tear film and slit lamp with cobalt blue filtered light examination is performed: breakup is determined by a dark spot forming in the tear film. Normal BUT is greater than 10 s [2, 6, 9, 22, 28]. Devices using computer-analyzed reflections from the cornea has also been used for noninvasive tear stability analysis (noninvasive tear film break-up time NITBUT) [9, 28, 32, 33, 34] Figure 1—(3).
\nThe Schirmer test is described as “test to measure change in tear volume (production)” [9, 22]. A small strip of filter paper (5 × 35 mm) is placed on the margin of lower eyelid at the junction of the lateral and middle third of the lid. After 5 min, wetting of the strip is measured. If the test is performed without anesthesia-reflex tearing (e.g., tearing in response to a stimulus), the cutoff value is 5 mm; if the test is done after topical anesthesia-nonreflex (basal tears), the cutoff value is 3 mm [2, 6, 9, 22, 25, 28]. Although inter- and intraindividual differences were described, the range and absolute values are reduced in aqueous-deficient dry eye [7, 32]. Some clinicians use the phenol red thread test to measure tear volume; a small thread impregnated with phenol red dye is placed on the lower lid margin for 15 s. The normal value of the threat wetting is over 10 mm [9, 28, 32], Figure 1—(2).
\nThe tear film composition analysis includes measurements of tear osmolarity (TO) and levels of inflammatory mediators. Elevated osmolarity of the tear film is a characteristic for DED though there is no suggested cutoff value for SS-related DED and further investigations should be conducted to establish it [9, 28, 32, 35, 36]. There is positive correlation between TO and OSDI score and OSS and negative correlation between osmolarity and Schirmer I test [28, 37]. Some studies found that a higher TO was associated with lower OSDI score in SS patients that was connected with the less corneal sensitivity [35, 38, 39]. TO measurements of both eyes are recommended: in early stages of DED, transient lower TO was noted; the effect was asymmetrical and this effect was not seen in subject without DED [28].
\nMeasurements of inflammatory mediators in the tear film help to identify the inflammatory reaction and the severity of DED [22, 28, 38]. The levels of various cytokines (TNF-α, IL-1α, IL-1ß, IL-6, IL-8, IL-10, IL-12P70, IL-13, MIP-1α, IFN-γ) and MMP-9 in tears of DED patients are significantly higher than those in normal people [22, 28, 40, 41]. Statistical differences among subclasses of DED for IL-8 and TNF-α were observed and it could be significant for diagnosing and treatment of DED [40]. The activity of cathepsin S (CTSS) in tears and the level of HLA-Dr in impression cytology were higher in patients with SS than in patients with non-SS DED and healthy subjects [22].
\nOcular surface evaluation is commonly clinically performed with the instillation of topical dyes. Fluorescein and lissamine green (or rose bengal) are vital dyes used to determine the integrity of the cornea and conjunctiva. Fluorescein is used for corneal examination (it stains punctate erosions), lissamine green (or rose Bengal) for conjunctival staining (both dyes stain mucus strands, filaments, and areas of epithelium unprotected by normal glycocalyx) [2, 6, 9, 22, 28]. Staining indicates corneal surface disease: greater staining means greater severity of DED. Conjunctival staining usually occurs before corneal staining, medial before temporal conjunctival staining [9, 28]. To evaluate and grade staining there are several systems such as 1995 NEI/industry Workshop System, the Oxford System, the van Bijsterveld system, the Ocular Staining Score (OSS) developed by SICCA [9, 22, 25, 28, 32] Figure 1—(4,5).
\nMeibomian gland dysfunction (MGD) is defined as: “a chronic, diffuse abnormality of the Meibomian glands, commonly characterized by terminal duct obstruction and/or qualitative/quantitative changes in the glandular secretion; this may result in alteration of the tear film, symptoms of eye irritation, clinically apparent inflammation, and ocular surface disease” [22, 41, 42]. MGD is the common cause of evaporative DED. Studies of SS patients found that MGD is common problem of them; they have higher Meibomian gland dropout scores compared with healthy group and worse Meibomian gland expressibility compared to non-SS DED patients [22, 24, 43]. The lipid layer is an important factor for ocular surface health and tear film stability [22, 44]. The thickness of this layer (lipid layer thickness LLT) is changed in DED and MGD; healthy subjects have LLT thinner than DED [22, 24, 45, 46, 47].
\nImaging of the ocular surface is a valuable tool to document and determine changes, as well as differentiate aqueous-deficient and evaporative DED. New devices perform minimally invasive objective measurements (no drops, no touching of the eye) of NITBUT, TMH, images of the Meibomian glands (meibography), bulbar redness, and LLT [9, 22, 47, 48, 49, 50].
\nAn in vivo confocal study demonstrated morphologic changes in corneas of SS patients: a decrease in central corneal thickness was hypothesized to be due to inflammatory process, a reduced number of subbasal plexus fibers may explain the phenomenon of decreased corneal sensitivity [51, 52].
\nDry eye from SS is more severe than idiopathic one, so effective in idiopathic DED treatment may or may not work in SS. After diagnosing SS, the aim of the treatment is to maintain the tear film integrity through preservation, augmentation, and/or replacement of the deficient tear secretion [28, 51, 52]. There are many different therapies for DED, but there is no one treatment that works for everybody [22, 28, 32, 53, 54]. Though management approach of DED has changed over the years, some principles persist [28, 32, 54]. The treatment strategy is based upon the severity of DED and patients response to each added therapy. It includes patients’ education, tears supplementation, management of MGD, inflammation of the ocular surface, and/or associated systemic disease [28, 32, 54].
\nGood cooperation of the DED patient requires understanding by them the disease (chronic), the aggravating factors (e.g., cigarette smoke, dry heating air, air conditioning, low humidity, pollutions, systemic medications that reduce tear secretion), and the management strategy (long-term and possibly slow to take effect). Some modifications of environment and activities of daily living can improve patients’ quality of life [28, 32, 54, 55].
\nArtificial tears are a standard of therapy for all severity grades of DED. The aim of this therapy in SS is to add tear film volume, to increase time of tear supplement on ocular surface and to reduce friction between lid and globe [28].
\nThese preparations are not similar to natural tears: the main ingredients of them are lubricants or viscosity agents. Tear supplements varied in formulas: some of them include electrolytes, which are in normal tears to prevent ocular surface damage, some of them are hypotonic or distribute between the tear film and intracellular fluid to protect against the pro-inflammatory effect of tears hyperosmolarity. They are based on polyvinyl alcohol, povidone, hydroxypropyl guar, cellulose derivatives, and hyaluronic acid. To mimic lipid component of tears triglycerides, phospholipids, and castor oil are used. Depending on viscosity of the lubricant (macromolecular complexes that increase the residence time of the supplement in the tear film) and thickness of supplement they may cause blurred vision; gels are more viscous than solutions, ophthalmic ointments are the thickest of lubrications. Typically, ointments are used before bedtime to provide DED symptoms, enabling sleep [28, 32, 54, 56, 57].
\nPreservatives (benzalkonium chloride or EDTA) in the tear supplements are potentially toxic to the ocular surface (epitheliotoxic). The toxicity of them increases in patients with DED because of frequent use of drops and decreased tears volume. The usage of artificial tears more than 4–6 times a day requires preservative-free unit dose vials [28, 54, 58].
\nThere is wide variety of tear supplements but none is clearly superior. “The main variables in the formulation of ocular lubricants regard the concentration of and choice of electrolytes, the osmolarity and the type of viscosity/polymeric system, the presence or absence of preservative, and, if present, the type of preservative” [28, 54].
\nLong-acting ocular surface lubrication is also achievable through the hydroxypropyl cellulose insert usage. The insert is placed in the inferior conjunctival fornix and dissolves at body temperature. Thickening the tear film it decreases the need for frequent topical lubrication, used at bedtime it substitutes the ointment [28, 54, 59].
\nSince inflammation plays a key role in the pathogenesis of DED, many anti-inflammatory therapies have been evaluated in clinical trials and animal models. Better control of inflammatory reaction means DED symptoms and signs improvement.
\nThere are some studies on short-term topical use of steroids in patients with SS and DED [9, 22, 28, 54, 60]. A 2- to 4-week course of treatment in patients with moderate to severe DED showed an improvement in both symptoms and signs: decreased symptom score, conjunctival hyperemia and corneal fluorescein staining, better TFBUT and Schirmer test measurements, higher numbers of goblet cells on impression cytology and lower numbers of inflammatory cells [28, 52, 60, 61, 62, 63]. Topical steroids as a pulse therapy was noted as safe and effective one [60]. There are possible complications associated with long-term steroids usage: cataract, glaucoma, and infections. Elevated intraocular pressure and posterior subcapsular cataracts were described in patients using steroids over 3 months [28, 64].
\nCyclosporine A (CsA) is one of the powerful anti-T-cell immunosuppressive agents, but with no bone marrow suppression. The mechanism of action includes both inhibition of T-lymphocyte activation and other inhibitory properties, as the ability to inhibit apoptosis of other cells [28, 54, 65, 66]. Topical CsA reduce the cell-mediated inflammatory reactions [66] that results in improvement in symptoms (blurred vision, ocular dryness, foreign body sensation, and epiphora), reduction of fluorescein staining, better tear production (Schirmer test), reduction of pro-inflammatory cytokine and HLA-DR expression, increase of goblet cell density [2, 22, 28, 32, 67, 68]. Better tears production is probably connected with local release of parasympathetic neurotransmitters [32, 69]. CsA instilled to the conjunctival sac seems to be the first therapeutic (not only symptomatic as others) treatment for patients with moderate to severe DED due to aqueous deficiency [66, 70].
\nThe use of topical CsA for evaporative DED due to MGD is recommended by the International Tear Film and Ocular Surface Workshop on Meibomian Gland Dysfunction [28, 54, 71]. Traditional treatment of posterior blepharitis and MGD include lid hygiene, massages, hot compresses, low-dose tetracyclines, and topical antibiotics [28, 32, 71]. In some studies, the CsA-treated patients had a greater decrease in the number of obstructed Meibomian gland, improvement in the viscosity of Meibomian gland secretion, TFBUT, staining scores, and Schirmer scores than those treated in traditional way [28, 72, 73].
\nLong-term study confirmed safety of topical cyclosporine in 3-year follow-up [28, 74].
\nLifitegrast is a direct competitive antagonist of binding of lymphocyte function-associated antigen 1 (LFA-1) to intracellular adhesion molecule 1 (ICAM-1). Interaction between LFA-1 and ICAM-1 leads to T-lymphocyte adhesion to endothelial cells, migration to tissue, antigen presentation and recognition facilitating the formation of an immunological synapse. It releases inflammatory mediators, cytokines, chemokines, TNF-α, and IL-1 which are responsible for perpetuation and intensification DED inflammation [2, 22, 75, 76, 77, 78, 79]. The clinical efficacy of lifitegrast in patients with DED has been reported: improvement in symptom scores and ocular staining score in patients using it for 12 weeks. No serious ocular adverse events occurred [22, 75, 76, 77, 78, 79]. However, there are no studies comparing lifitegrast and other anti-inflammatory agents, evaluating whether lifitegrast in combination therapy could work better in DED—those problems need further studies [79].
\nSerum is the fluid component of full blood that remains after clotting [54]. Human serum is similar to natural tears and contains many important components as: (1) epithelial growth factor EGF (acceleration of epithelial cell migration and anti-apoptotic effects); (2) transforming growth factor-ß/TGF-ß (involved in the epithelial and stromal repair process); (3) vitamin A (prevent epithelial squamous metaplasia and modulate the expression of thrombospondin-1); (4) thrombospondin-2, vascular endothelial growth factor A/VEGF-A, metallopeptidase-9 which with TGF-ß promote wound healing; (5) albumin (anti-apoptotic activity); (6) α-2 macroglobulin (exhibits anti-collagenase activity); (7) fibronectin (involved in cell migration); (8) substance P and insulin-like growth factor (potential role in corneal epithelial migration and adhesion); and (9) immunoglobulins and lysozyme (bactericidal and bacteriostatic effect). Significant improvement in symptoms, fluorescein TFBUT, and ocular surface staining score were reported after autologous serum drops treatment [28, 54, 80, 81, 82]. However, some studies reported no significant advantage in tear film stability, Schirmer test, or fluorescein staining in the use of AS over AF [83, 84, 85]. It is free of preservatives and has osmolarity and biomechanical properties similar to natural tears [54, 80, 84].
\nPlasma rich in growth factors (PRGF) and platelet-rich plasma (PRP) have been reported as successful treatment in DED patients [54, 84, 85]. Both of them (PRGF and PRP) are liberated from the platelets during preparation. Those components help in the proliferation, migration, and differentiation of corneal epithelial cells [84, 85, 86, 87]. Both PRGF and PRP are preservative-free, well tolerated with almost no side effects [84, 85, 86, 87]. Further investigations to compare them with other hemoderivatives and with commercial artificial tear eye drops are necessary.
\n“A secretagogue is a substance that causes another substance to be secreted” [28, 54]. Oral pilocarpine and cevimeline are indicated for treatment of dryness in SS. As muscarinic agonists, they stimulate secretion of saliva, aqueous tear from lacrimal glands, conjunctival epithelium, and mucin from goblet cells [52]. Some studies have shown their effectiveness in DED treatment in SS patients. The oral 10–30 mg/day of pilocarpine improves DED symptoms in comparison to placebo or artificial tears as well as a punctal occlusion. While there was no improvement in Schirmer test result, the patients with oral pilocarpine showed better score of ocular staining. Moreover, in SS patients with oral pilocarpine treatment increased the number of conjunctival goblet cells [28, 54, 88, 89]. The oral cevimeline dosage of 20–30 mg every 8 h improved ocular staining scores and TFBUT but no significant differences in lacrimal flow rates were found [28, 54, 90].
\nTopical secretagogues are approved in treatment of dryness in Japan. Drugs as: 2% rebamipide which increases mucin level over the conjunctiva and cornea (improves TFBUT), 3% diquafosol tetrasodium which increases mucin and fluid secretion (improves ocular staining) are introduced for DED topical treatment in clinical practice [22, 54, 91].
\nThe idea of punctal/canalicular occlusion is to block tear drainage from the ocular surface and use patients’ own tears to maintain the lubrication of the eye. It also helps maintain instilled artificial tears longer [28, 54, 91]. The concept of permanent cautery lacrimal puncta occlusion for DED treatment was described in 1936, first dissolvable implants were used in 1961, but the modern idea of punctal plug use began with Freeman report in 1975 [54, 91, 92, 93]. Plugs are made of variety of materials and design, they can be absorbable (last 3 days to 6 months) or non-absorbable. The ideal occluder should be easy to place, block the drainage effectively, be biocompatible, long lasting, easy reversible, and have low potential for infection [28, 54, 91]. Punctal/canalicular plugs are common second-line treatment in aqua-deficiency DED. A comparison of plugs versus artificial tears in patients with SS and DED demonstrated that both treatments improved symptom scores, corneal staining and TFBUT, but Schirmer test and TFBUT were statistically more improved in plugs’ group [28, 94].
\nTherapeutic contact lenses (TCL) are used to promote corneal healing, protect the ocular surface from the lids and environment, reduce desiccation, and relieve discomfort [22, 28, 54]. Silicone-hydrogel materials have higher oxygen transmission than hydrogels. Some of soft silicone-hydrogel contact lenses are approved for therapeutic wear and could be useful in primary and secondary Sjögren syndrome for relief from discomfort and blurred vision. There is no literature on the use TCL in the treatment of DED in SS, but reports on such a treatment in other entities or ocular surface problems are encouraging [28, 52, 54, 95].
\nBandage contact lenses (BCL) are large-diameter, rigid, gas-permeable lenses with scleral fixation. Retention of a fluid reservoir over the cornea and no corneal touch are the reason of the therapeutic effect of BCL. The use of BCL specifically in SS patients is not described, but some patients with SS were included in the groups in which benefit were demonstrated [28, 52, 54, 96].
\nSevere symptoms of eye surface irritation in patients with mucus filaments/strands are the reason to use topical mucolytic solution. Topical N-acetylcysteine (10–20% aqueous solution) therapy for 2–4 weeks usually resolves the problem [28, 97].
\nEssential fatty acids (EFA) are polyunsaturated fats that are not synthesized by humans. Dietary supplementation (e.g., fish oil or flax seed oil or nutritional supplements) with omega-3 EFA as anti-inflammatory therapy is considered. Improvement in DED symptoms and signs with both oral and topical omega-3 EFA was described although there is nothing specific regarding the use for SS [22, 28, 97–8]. Gamma-linolenic acid is an omega-6 EFA with anti-inflammatory effect in chronic inflammatory diseases. An inverse association between it and levels of anti-SSA/anti-Ro antibodies were described. Improvement of symptoms and corneal staining after oral supplementation with omega-6 EFA were found [52, 99, 100].
\nMGD treatment include eyelid hygiene, hot compresses, eyelid massages, thermal pulsation treatment, anti-inflammatory, and antibacterial therapy (e.g., oral tetracyclines and EFA omega-3, topical azithromycin and EFA omega-3 [22, 28, 54, 71, 97, 98, 101]). In patients with MGD, melting point of meibomian lipids rises, which is why hot compresses, warming masks and goggles, infrared heaters, and eyelid massage led to clinical improvement with tear film stability and lipid thickness of the tear film (reduced blockage of meibomian gland excretory ducts and improvement of the meibomian secretion) [32, 54, 71, 101, 102, 103]. Tetracyclines are bacteriostatic antibiotics with anti-inflammatory effect (reduction of the synthesis and activity of matrix metalloproteinases, production of IL-1 and TNF-α, activity of collagenases and B-cell activation). A low-dose treatment for 6–12 weeks improves tear film stability, tear production, and symptoms (higher dosages are connected with higher rate of adverse events) [32, 102, 103, 104, 105]. Macrolides (azithromycin) have both bacteriostatic and anti-inflammatory effect. They improve meibomian gland function and symptoms, reduce bacterial colonization of eyelid and normalize meibomian gland secretion [32, 106, 107].
\nTo reduce degree of ocular surface exposure for environmental factors and for evaporation a partial closure/closure of the eyelid may be indicated: for short periods, botulinum injections have been used; in other cases, surgical procedures may be considered [28, 108].
\nThe treatment with systemic immunosuppression in patients with DED and SS requires clinical trials to assess it [2, 22, 52]. Antimalarials (hydroxychloroquine and chloroquine), in some studies, were found to have benefits for SS DED, but in others, there was no change (test Schirmer 1, FTBUT) between baseline and the end point; OSDI improved, but there was no statistical difference between treating group and placebo [2, 109, 110, 111]. Methotrexate (MTX) has well-documented efficacy in uveitis and scleritis, but there is no data that confirm it works in SS DED: one case report on improvement with MTX therapy [2, 112]. In one open-label study, improvement in symptoms but no changes in signs of DED in patients with pSS treated with mycophenolate mofetil were reported [2, 113]. Rituximab (anti-CD 20 monoclonal antibody) in some studies improved symptoms of DED, in others there was no statistical significance on the final results of ocular dryness and Schirmer 1 testing [2, 52, 114]. There was no improvement in both symptoms and signs after etanercept therapy [52, 115], abatacept (CTLA4-Ig) in some studies improved results of Schirmer 1 test, in others there were changes in FTBUT [2, 116].
\nThere are some studies on the use of hormonal therapy in patients with DED. Association of low androgen levels with lacrimal gland inflammation and lacrimal insufficiency were found, consequently androgen supplementation could be a potential therapy in DED [97, 117]. Studies on systemic estrogen and estrogen-androgen therapy revealed that estrogen-only therapy may intensify ocular irritation (no benefits in symptoms and signs); however, topical estrogen therapy seems to be beneficial for DED because of the influence on ocular epithelial cells. Combined estrogen-androgen therapy improves symptoms of DED [97, 118, 119, 120]. Although dehydroepiandrosterone (DHEA) may replenish suppressed hormonal levels in pSS and improve sicca symptoms, first data on DED symptoms and signs after DHEA therapy have not revealed improvement [95, 121, 122].
\nIn literature, we can find some more possibilities of DED treatment in SS patients, but they are published as case reports or clinical studies. Neurostimulation of nasolacrimal pathway stimulates lacrimal gland secretion that improves scores of Schirmer I test and results of ocular staining. A new device for intranasal neurostimulation provides small electrical pulses to stimulate production of patients’ tears [22, 123]. Local radiotherapy to the lacrimal gland was reported as a successful treatment in a patient with SS and lacrimal gland involvement [51, 124]. There are experimental studies on topical administration of lacritin (tear glycoprotein with prosecretory, prosurvival, and mitogenic properties) and interleukin-1 receptor antagonist—anakinra (targeting IL-1/IL-1R1 signaling pathway) in aqua-deficiency DED and both of them are promising for future [125, 126]. Therapy with oral lactoferrin (tear protein modulating oxidative stress and regulating microbes) improved corneal sensitivity compared to placebo [52, 127], as well as herbs used in traditional Chinese medicine revealed beneficial effect for symptoms and Schirmer 1 test score compared to placebo [52, 127, 128], but both methods are limited in routine clinic because of the lack of explanation of molecular mechanisms or target limits [52].
\nDry eye disease is an inseparable part of the both types of Sjögren’s syndrome. There is no specific test to diagnose it—for everyday practice, several tests are used to diagnose and to interpret the severity of the problem. Moreover, though it is more severe than in other diseases, there is no specific test for DED in SS.
\nThe treatment of DED in SS is also the same as in other patients. Patients are treated with both topical and systemic therapies. There are some trials to use immunosuppressive agents for DED in SS to provide relief to eye dryness symptoms, but there are not enough verified studies on it.
\nBoth in diagnostic and therapeutic problems of DED, there are still challenges for the future and need further multicenter, double-blind, randomized studies.
\nThe Internet has irrevocably changed the dynamics of scholarly communication and publishing. Consequently, we find it necessary to indicate, unambiguously, our definition of what we consider to be a published scientific work.
",metaTitle:"Prior Publication Policy",metaDescription:"Prior Publication Policy",metaKeywords:null,canonicalURL:"/page/prior-publication-policy",contentRaw:'[{"type":"htmlEditorComponent","content":"A significant number of working papers, early drafts, and similar work in progress are openly shared online between members of the scientific community. It has become common to announce one’s own research on a personal website or a blog to gather comments and suggestions from other researchers. Such works and online postings are, indeed, published in the sense that they are made publicly available. However, this does not mean that if submitted for publication by IntechOpen they are not original works. We differentiate between reviewed and non-reviewed works when determining whether a work is original and has been published in a scholarly sense or not.
\\n\\nThe significance of Peer Review cannot be overstated when it comes to defining, in our terms, what constitutes a published scientific work. Peer Review is widely considered to be the cornerstone of modern publishing processes and the key value-adding contribution to a scholarly manuscript that a publisher can make.
\\n\\nOther than the issue of originality, research misconduct is another major issue that all publishers have to address. IntechOpen’s Retraction & Correction Policy and various publication ethics guidelines identify both redundant publication and (self)plagiarism to fall within the definition of research misconduct, thus constituting grounds for rejection or the issue of a Retraction if the work has already been published.
\\n\\nIn order to facilitate the tracking of a manuscript’s publishing history and its development from its earliest draft to the manuscript submitted, we encourage Authors to disclose any instances of a manuscript’s prior publication, whether it be through a conference presentation, a newspaper article, a working paper publicly available in a repository or a blog post.
\\n\\nA note to the Academic Editor containing detailed information about a submitted manuscript’s previous public availability is the preferred means of reporting prior publication. This helps us determine if there are any earlier versions of a manuscript that should be disclosed to our readers or if any of those earlier versions should be cited and listed in a manuscript’s references.
\\n\\nSome basic information about the editorial treatment of different varieties of prior publication is laid out below:
\\n\\n1. CONFERENCE PAPERS & PRESENTATIONS
\\n\\nGiven that conference papers and presentations generally pass through some sort of peer or editorial review, we consider them to be published in the accepted scholarly sense, particularly if they are published as a part of conference proceedings.
\\n\\nAll submitted manuscripts originating from a previously published conference paper must contain at least 50% of new original content to be accepted for review and considered for publication.
\\n\\nAuthors are required to report any links their manuscript might have with their earlier conference papers and presentations in a note to the Academic Editor, as well as in the manuscript itself. Additionally, Authors should obtain any necessary permissions from the publisher of their conference paper if copyright transfer occurred during the publishing process. Failure to do so may prevent Us from publishing an otherwise worthy work.
\\n\\n2. NEWSPAPER & MAGAZINE ARTICLES
\\n\\nNewspaper and magazine articles usually do not pass through any extensive peer or editorial review and we do not consider them to be published in the scholarly sense. Articles appearing in newspapers and magazines rarely possess the depth and structure characteristic of scholarly articles.
\\n\\nSubmitted manuscripts stemming from a previous newspaper or magazine article will be accepted for review and considered for publication. However, Authors are strongly advised to report any such publication in an accompanying note to the External Editor.
\\n\\nAs with the conference papers and presentations, Authors should obtain any necessary permissions from the newspaper or magazine that published the work, and indicate that they have done so in a note to the External Editor.
\\n\\n3. GREY LITERATURE
\\n\\nWhite papers, working papers, technical reports and all other forms of papers which fall within the scope of the ‘Luxembourg definition’ of grey literature do not pass through any extensive peer or editorial review and we do not consider them to be published in the scholarly sense.
\\n\\nAlthough such papers are regularly made publicly available via personal websites and institutional repositories, their general purpose is to gather comments and feedback from Authors’ colleagues in order to further improve a manuscript intended for future publication.
\\n\\nWhen submitting their work, Authors are required to disclose the existence of any publicly available earlier drafts in a note to the Academic Editor. In cases where earlier drafts of the submitted version of the manuscript are publicly available, any overlap between the versions will generally not be considered an instance of self-plagiarism.
\\n\\n4. SOCIAL MEDIA, BLOG & MESSAGE BOARD POSTINGS
\\n\\nWe feel that social media, blogs and message boards are generally used with the same intention as grey literature, to formulate ideas for a manuscript and gather early feedback from like-minded researchers in order to improve a particular piece of work before submitting it for publication. Therefore, we do not consider such internet postings to be publication in the scholarly sense.
\\n\\nNevertheless, Authors are encouraged to disclose the existence of any internet postings in which they outline and describe their research or posted passages of their manuscripts in a note to the Academic Editor. Please note that we will not strictly enforce this request in the same way that we would instructions we consider to be part of our conditions of acceptance for publication. We understand that it may be difficult to keep track of all one’s internet postings in which the researcher´s current work might be mentioned.
\\n\\nIn cases where there is any overlap between the Author´s submitted manuscript and related internet postings, we will generally not consider it to be an instance of self-plagiarism. This also holds true for any co-Author as well.
\\n\\nFor more information on this policy please contact permissions@intechopen.com.
\\n\\nPolicy last updated: 2017-03-20
\\n"}]'},components:[{type:"htmlEditorComponent",content:'A significant number of working papers, early drafts, and similar work in progress are openly shared online between members of the scientific community. It has become common to announce one’s own research on a personal website or a blog to gather comments and suggestions from other researchers. Such works and online postings are, indeed, published in the sense that they are made publicly available. However, this does not mean that if submitted for publication by IntechOpen they are not original works. We differentiate between reviewed and non-reviewed works when determining whether a work is original and has been published in a scholarly sense or not.
\n\nThe significance of Peer Review cannot be overstated when it comes to defining, in our terms, what constitutes a published scientific work. Peer Review is widely considered to be the cornerstone of modern publishing processes and the key value-adding contribution to a scholarly manuscript that a publisher can make.
\n\nOther than the issue of originality, research misconduct is another major issue that all publishers have to address. IntechOpen’s Retraction & Correction Policy and various publication ethics guidelines identify both redundant publication and (self)plagiarism to fall within the definition of research misconduct, thus constituting grounds for rejection or the issue of a Retraction if the work has already been published.
\n\nIn order to facilitate the tracking of a manuscript’s publishing history and its development from its earliest draft to the manuscript submitted, we encourage Authors to disclose any instances of a manuscript’s prior publication, whether it be through a conference presentation, a newspaper article, a working paper publicly available in a repository or a blog post.
\n\nA note to the Academic Editor containing detailed information about a submitted manuscript’s previous public availability is the preferred means of reporting prior publication. This helps us determine if there are any earlier versions of a manuscript that should be disclosed to our readers or if any of those earlier versions should be cited and listed in a manuscript’s references.
\n\nSome basic information about the editorial treatment of different varieties of prior publication is laid out below:
\n\n1. CONFERENCE PAPERS & PRESENTATIONS
\n\nGiven that conference papers and presentations generally pass through some sort of peer or editorial review, we consider them to be published in the accepted scholarly sense, particularly if they are published as a part of conference proceedings.
\n\nAll submitted manuscripts originating from a previously published conference paper must contain at least 50% of new original content to be accepted for review and considered for publication.
\n\nAuthors are required to report any links their manuscript might have with their earlier conference papers and presentations in a note to the Academic Editor, as well as in the manuscript itself. Additionally, Authors should obtain any necessary permissions from the publisher of their conference paper if copyright transfer occurred during the publishing process. Failure to do so may prevent Us from publishing an otherwise worthy work.
\n\n2. NEWSPAPER & MAGAZINE ARTICLES
\n\nNewspaper and magazine articles usually do not pass through any extensive peer or editorial review and we do not consider them to be published in the scholarly sense. Articles appearing in newspapers and magazines rarely possess the depth and structure characteristic of scholarly articles.
\n\nSubmitted manuscripts stemming from a previous newspaper or magazine article will be accepted for review and considered for publication. However, Authors are strongly advised to report any such publication in an accompanying note to the External Editor.
\n\nAs with the conference papers and presentations, Authors should obtain any necessary permissions from the newspaper or magazine that published the work, and indicate that they have done so in a note to the External Editor.
\n\n3. GREY LITERATURE
\n\nWhite papers, working papers, technical reports and all other forms of papers which fall within the scope of the ‘Luxembourg definition’ of grey literature do not pass through any extensive peer or editorial review and we do not consider them to be published in the scholarly sense.
\n\nAlthough such papers are regularly made publicly available via personal websites and institutional repositories, their general purpose is to gather comments and feedback from Authors’ colleagues in order to further improve a manuscript intended for future publication.
\n\nWhen submitting their work, Authors are required to disclose the existence of any publicly available earlier drafts in a note to the Academic Editor. In cases where earlier drafts of the submitted version of the manuscript are publicly available, any overlap between the versions will generally not be considered an instance of self-plagiarism.
\n\n4. SOCIAL MEDIA, BLOG & MESSAGE BOARD POSTINGS
\n\nWe feel that social media, blogs and message boards are generally used with the same intention as grey literature, to formulate ideas for a manuscript and gather early feedback from like-minded researchers in order to improve a particular piece of work before submitting it for publication. Therefore, we do not consider such internet postings to be publication in the scholarly sense.
\n\nNevertheless, Authors are encouraged to disclose the existence of any internet postings in which they outline and describe their research or posted passages of their manuscripts in a note to the Academic Editor. Please note that we will not strictly enforce this request in the same way that we would instructions we consider to be part of our conditions of acceptance for publication. We understand that it may be difficult to keep track of all one’s internet postings in which the researcher´s current work might be mentioned.
\n\nIn cases where there is any overlap between the Author´s submitted manuscript and related internet postings, we will generally not consider it to be an instance of self-plagiarism. This also holds true for any co-Author as well.
\n\nFor more information on this policy please contact permissions@intechopen.com.
\n\nPolicy last updated: 2017-03-20
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On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. 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Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. 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After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. He has contributed in stochastic estimation of control area especially, in the Multiple Target Tracking and Interactive Multiple Model (IMM) research, Ball & Beam Control Problem, Robotics, Levitation Control. He has contributed in developing Algorithms for Fingerprint Matching, Computer Vision and Face Recognition. He has been supervising Pattern Recognition, Formal Languages and Distributed Processing projects for several years. He has reviewed many books on Management, Computer Science. Currently, he is an active and permanent reviewer for many international conferences and symposia and the program committee member for many international conferences.\nIn teaching he has taught the core computer science subjects like, Digital Design, Real Time Embedded System Programming, Operating Systems, Software Engineering, Data Structures, Databases, Compiler Construction. 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Promising WBG materials are silicon carbide (SiC), gallium nitride (GaN), diamond (C), gallium oxide (Ga2O3) and aluminum nitride (AlN). They can operate at higher voltages, temperatures, and switching frequencies with greater efficiencies compared to existing Si, in power electronics. These characteristics can reduce energy consumption, which is critical for national economic, health, and security interests. However, increased voltage blocking capability and trend toward more compact packaging technology for high-power density WBG devices can enhance the local electric field that may become large enough to raise partial discharges (PDs) within the module. High activity of PDs damages the insulating silicone gel, lead to electrical insulation failure and reduce the reliability of the module. Among WBG devices, electrical insulation weaknesses in WBG-based Insulated Gate Bipolar Transistor (IGBT) have been more investigated. 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Based on the huge amount of supported heterogeneous cores, efficient communication between the associated processors has to be considered at all levels of the system design to ensure global interconnection. This can be achieved through a design-friendly, flexible, scalable, and high-performance interconnection architecture. It is noteworthy that the interconnections between multiple cores on a chip present a considerable influence on the performance and communication of the chip design regarding the throughput, end-to-end delay, and packets loss ratio. Although hierarchical architectures have addressed the majority of the associated challenges of the traditional interconnection techniques, the main limiting factor is scalability. Network-on-Chip (NoC) has been presented as a scalable and well-structured alternative solution that is capable of addressing communication issues in the on-chip systems. In this context, several NoC topologies have been presented to support various routing techniques and attend to different chip architectural requirements. This book chapter reviews some of the existing NoC topologies and their associated characteristics. Also, application mapping algorithms and some key challenges of NoC are considered.",book:{id:"10269",slug:"network-on-chip-architecture-optimization-and-design-explorations",title:"Network-on-Chip",fullTitle:"Network-on-Chip - Architecture, Optimization, and Design Explorations"},signatures:"Isiaka A. Alimi, Romil K. Patel, Oluyomi Aboderin, Abdelgader M. Abdalla, Ramoni A. Gbadamosi, Nelson J. Muga, Armando N. Pinto and António L. Teixeira",authors:[{id:"208236",title:"Dr.",name:"Isiaka",middleName:"Ajewale",surname:"Alimi",slug:"isiaka-alimi",fullName:"Isiaka Alimi"},{id:"208242",title:"Dr.",name:"António L.",middleName:null,surname:"Teixeira",slug:"antonio-l.-teixeira",fullName:"António L. 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Gbadamosi"}]},{id:"62153",title:"Electrical Insulation Weaknesses in Wide Bandgap Devices",slug:"electrical-insulation-weaknesses-in-wide-bandgap-devices",totalDownloads:1266,totalCrossrefCites:23,totalDimensionsCites:26,abstract:"The power electronics research community is balancing on the edge of a game-changing technological innovation: as traditionally silicon (Si) based power semiconductors approach their material limitations, next-generation wide bandgap (WBG) power semiconductors are poised to overtake them. Promising WBG materials are silicon carbide (SiC), gallium nitride (GaN), diamond (C), gallium oxide (Ga2O3) and aluminum nitride (AlN). They can operate at higher voltages, temperatures, and switching frequencies with greater efficiencies compared to existing Si, in power electronics. These characteristics can reduce energy consumption, which is critical for national economic, health, and security interests. However, increased voltage blocking capability and trend toward more compact packaging technology for high-power density WBG devices can enhance the local electric field that may become large enough to raise partial discharges (PDs) within the module. High activity of PDs damages the insulating silicone gel, lead to electrical insulation failure and reduce the reliability of the module. Among WBG devices, electrical insulation weaknesses in WBG-based Insulated Gate Bipolar Transistor (IGBT) have been more investigated. The chapter deals with (a) current standards for evaluation of the insulation systems of power electronics modules, (b) simulation and modeling of the electric field stress inside modules, (c) diagnostic tests on modules, and (d) PD control methods in modules.",book:{id:"6749",slug:"simulation-and-modelling-of-electrical-insulation-weaknesses-in-electrical-equipment",title:"Simulation and Modelling of Electrical Insulation Weaknesses in Electrical Equipment",fullTitle:"Simulation and Modelling of Electrical Insulation Weaknesses in Electrical Equipment"},signatures:"Mona Ghassemi",authors:[{id:"235732",title:"Dr.",name:"Mona",middleName:null,surname:"Ghassemi",slug:"mona-ghassemi",fullName:"Mona Ghassemi"}]},{id:"61792",title:"Thermal Modelling of Electrical Insulation System in Power Transformers",slug:"thermal-modelling-of-electrical-insulation-system-in-power-transformers",totalDownloads:1340,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"Temperature is one of the limiting factors in the application of power transformers. According to IEC 60076-7 standard, a temperature increase of 6°C doubles the insulation ageing rate, reducing the expected lifetime of the device. Power losses of the transformer behave as a heating source, and the insulating liquids act as a coolant circulating through the windings and dissipating heat. For these reasons, thermal modelling becomes an important fact of transformer design, and both manufacturers and utilities consider it. Different techniques for thermal modelling have been developed and used for determining the hot-spot temperature, which is the highest temperature in the winding, and it is related with the degradation rate of the solid insulation. First models were developed as a first estimation for modelling the hot-spot temperature and the top-oil temperature. These models were based on thermal-electric analogy and are known as dynamic models. Other two different kinds of models are widely used for thermal modelling, known as Computational Fluid Dynamics (CFD) and Thermal Hydraulic Network Models (THNMs). These two techniques determine the temperature and velocity fields in the winding and in the insulating fluid. In this chapter, the different techniques for transformer thermal modelling will be introduced and described.",book:{id:"6749",slug:"simulation-and-modelling-of-electrical-insulation-weaknesses-in-electrical-equipment",title:"Simulation and Modelling of Electrical Insulation Weaknesses in Electrical Equipment",fullTitle:"Simulation and Modelling of Electrical Insulation Weaknesses in Electrical Equipment"},signatures:"Agustín Santisteban, Fernando Delgado, Alfredo Ortiz, Carlos J.\nRenedo and Felix Ortiz",authors:[{id:"24550",title:"Dr.",name:"Carlos",middleName:"J",surname:"Renedo",slug:"carlos-renedo",fullName:"Carlos Renedo"},{id:"26667",title:"Dr.",name:"Alfredo",middleName:null,surname:"Ortiz",slug:"alfredo-ortiz",fullName:"Alfredo Ortiz"},{id:"239344",title:"Ph.D. Student",name:"Agustín",middleName:null,surname:"Santisteban",slug:"agustin-santisteban",fullName:"Agustín Santisteban"},{id:"245139",title:"Dr.",name:"Fernando",middleName:null,surname:"Delgado",slug:"fernando-delgado",fullName:"Fernando Delgado"},{id:"245141",title:"Dr.",name:"Félix",middleName:null,surname:"Ortiz",slug:"felix-ortiz",fullName:"Félix Ortiz"}]},{id:"63042",title:"Typical Internal Defects of Gas-Insulated Switchgear and Partial Discharge Characteristics",slug:"typical-internal-defects-of-gas-insulated-switchgear-and-partial-discharge-characteristics",totalDownloads:1722,totalCrossrefCites:10,totalDimensionsCites:10,abstract:"Gas-insulated switchgear (GIS) is a common electrical equipment, which uses sulfur hexafluoride (SF6) as insulating medium instead of traditional air. It has good reliability and flexibility. However, GIS may have internal defects and partial discharge (PD) is then induced. PD will cause great harm to GIS and power system. Therefore, it is of great importance to study the intrinsic characteristics and detection of PD for online monitoring. In this chapter, typical internal defects of GIS and the PD characteristics are discussed. Several detection methods are also presented in this chapter including electromagnetic method, chemical method, and optical method.",book:{id:"6749",slug:"simulation-and-modelling-of-electrical-insulation-weaknesses-in-electrical-equipment",title:"Simulation and Modelling of Electrical Insulation Weaknesses in Electrical Equipment",fullTitle:"Simulation and Modelling of Electrical Insulation Weaknesses in Electrical Equipment"},signatures:"Fuping Zeng, Ju Tang, Xiaoxing Zhang, Siyuan Zhou and Cheng Pan",authors:[{id:"197319",title:"Prof.",name:"Xiaoxing",middleName:null,surname:"Zhang",slug:"xiaoxing-zhang",fullName:"Xiaoxing Zhang"},{id:"205017",title:"Prof.",name:"Ju",middleName:null,surname:"Tang",slug:"ju-tang",fullName:"Ju Tang"},{id:"210705",title:"Dr.",name:"Fuping",middleName:null,surname:"Zeng",slug:"fuping-zeng",fullName:"Fuping Zeng"},{id:"210707",title:"Dr.",name:"Cheng",middleName:null,surname:"Pan",slug:"cheng-pan",fullName:"Cheng Pan"},{id:"279579",title:"Dr.",name:"Siyuan",middleName:null,surname:"Zhou",slug:"siyuan-zhou",fullName:"Siyuan Zhou"}]},{id:"61773",title:"Modeling and Simulation of Rotating Machine Windings Fed by High-Power Frequency Converters for Insulation Design",slug:"modeling-and-simulation-of-rotating-machine-windings-fed-by-high-power-frequency-converters-for-insu",totalDownloads:1619,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Modern power systems include a considerable amount of power electronic converters related to the introduction of renewable energy sources, high-voltage direct current (HVDC) systems, adjustable speed drives, and so on. These components introduce repetitive pulses generated by the commutation of semiconductor switches, resulting in overvoltages with very steep fronts and high dielectric stresses. This phenomenon is one of the main causes of accelerated insulation aging of motors in power electronic-based systems. This chapter presents state-of-the-art computational tools for the analysis of motor windings excited by fast-front pulses related to the use of frequency converters based on pulse-width modulation (PWM). These tools can be applied for the accurate prediction of overvoltages and dielectric stresses required to propose insulation design improvements. In the case of the stress-grading system used in medium-voltage (MV) motors, transient finite-element method (FEM) is used to study the effect of fast pulses. It is shown how, by controlling the material properties and the design of the stress-grading systems, solutions to reduce the adverse effects of fast pulses from PWM-type inverters can be proposed.",book:{id:"6749",slug:"simulation-and-modelling-of-electrical-insulation-weaknesses-in-electrical-equipment",title:"Simulation and Modelling of Electrical Insulation Weaknesses in Electrical Equipment",fullTitle:"Simulation and Modelling of Electrical Insulation Weaknesses in Electrical Equipment"},signatures:"Fermin P. Espino Cortes, Pablo Gomez and Mohammed Khalil\nHussain",authors:[{id:"238065",title:"Associate Prof.",name:"Pablo",middleName:null,surname:"Gomez",slug:"pablo-gomez",fullName:"Pablo Gomez"},{id:"238796",title:"Dr.",name:"Fermin P.",middleName:null,surname:"Espino-Cortés",slug:"fermin-p.-espino-cortes",fullName:"Fermin P. Espino-Cortés"},{id:"245189",title:"Dr.",name:"Mohammed Khalil",middleName:null,surname:"Hussain",slug:"mohammed-khalil-hussain",fullName:"Mohammed Khalil Hussain"}]}],onlineFirstChaptersFilter:{topicId:"735",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:106,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517",scope:"Paralleling similar advances in the medical field, astounding advances occurred in Veterinary Medicine and Science in recent decades. These advances have helped foster better support for animal health, more humane animal production, and a better understanding of the physiology of endangered species to improve the assisted reproductive technologies or the pathogenesis of certain diseases, where animals can be used as models for human diseases (like cancer, degenerative diseases or fertility), and even as a guarantee of public health. Bridging Human, Animal, and Environmental health, the holistic and integrative “One Health” concept intimately associates the developments within those fields, projecting its advancements into practice. This book series aims to tackle various animal-related medicine and sciences fields, providing thematic volumes consisting of high-quality significant research directed to researchers and postgraduates. It aims to give us a glimpse into the new accomplishments in the Veterinary Medicine and Science field. 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After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",institutionURL:null,country:{name:"Portugal"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"19",title:"Animal Science",coverUrl:"https://cdn.intechopen.com/series_topics/covers/19.jpg",isOpenForSubmission:!0,editor:{id:"259298",title:"Dr.",name:"Edward",middleName:null,surname:"Narayan",slug:"edward-narayan",fullName:"Edward Narayan",profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",biography:"Dr. Edward Narayan graduated with Ph.D. degree in Biology from the University of the South Pacific and pioneered non-invasive reproductive and stress endocrinology tools for amphibians - the novel development and validation of non-invasive enzyme immunoassays for the evaluation of reproductive hormonal cycle and stress hormone responses to environmental stressors. \nDr. Narayan leads the Stress Lab (Comparative Physiology and Endocrinology) at the University of Queensland. A dynamic career research platform which is based on the thematic areas of comparative vertebrate physiology, stress endocrinology, reproductive endocrinology, animal health and welfare, and conservation biology. \nEdward has supervised 40 research students and published over 60 peer reviewed research.",institutionString:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null},{id:"20",title:"Animal Nutrition",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",isOpenForSubmission:!0,editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. He teaches various degree courses in zootechnics, sheep production, and agricultural sciences and natural resources.\n\nDr. Ronquillo’s research focuses on the evaluation of sustainable animal diets (StAnD), using native resources of the region, decreasing carbon footprint, and applying meta-analysis and mathematical models for a better understanding of animal production.",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null},{id:"28",title:"Animal Reproductive Biology and Technology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/28.jpg",isOpenForSubmission:!0,editor:{id:"177225",title:"Prof.",name:"Rosa Maria Lino Neto",middleName:null,surname:"Pereira",slug:"rosa-maria-lino-neto-pereira",fullName:"Rosa Maria Lino Neto Pereira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9wkQAC/Profile_Picture_1624519982291",biography:"Rosa Maria Lino Neto Pereira (DVM, MsC, PhD and) is currently a researcher at the Genetic Resources and Biotechnology Unit of the National Institute of Agrarian and Veterinarian Research (INIAV, Portugal). She is the head of the Reproduction and Embryology Laboratories and was lecturer of Reproduction and Reproductive Biotechnologies at Veterinary Medicine Faculty. She has over 25 years of experience working in reproductive biology and biotechnology areas with a special emphasis on embryo and gamete cryopreservation, for research and animal genetic resources conservation, leading research projects with several peer-reviewed papers. Rosa Pereira is member of the ERFP-FAO Ex situ Working Group and of the Management Commission of the Portuguese Animal Germplasm Bank.",institutionString:"The National Institute for Agricultural and Veterinary Research. Portugal",institution:null},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:14,paginationItems:[{id:"82457",title:"Canine Hearing Management",doi:"10.5772/intechopen.105515",signatures:"Peter M. 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She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. 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She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. 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