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It innervates all superficial muscles of the face and scalp, the contraction of which is responsible for all our numerous facial expressions like anger, pain, fear, smile, etc. Facial disfigurement resulting from facial nerve disorders can affect the physical, psychological, and emotional integrity of an individual. This might result in social, occupational, and educational handicap. The facial nerve is one of the most common cranial nerves implicated by disorders. It is a mixed nerve, which carries motor, sensory, and parasympathetic fibers. The motor fiber-innervated muscles developed from second branchial arch, the sensory fibers transmit the special sense of taste, and the parasympathetic fibers supply the submandibular, sublingual, and lacrimal glands [1]. Embryologically speaking, it is formed very early within the acousticofacial complex from the second branchial arch [2]. Facial nerve consists of the juxtaposition of somatic and branchial elements of the cranial nerve nuclei, in particular, accounting for trigeminal and facial nerve anastomosis [3]. A wide variety of disorders can involve the facial nerve including congenital, traumatic, infectious, inflammatory, and neoplastic disorders.
\nThe anatomy of the facial nerve is the most complex among other cranial nerves. It composed of approximately 10,000 neurons. Seven thousands of these fibers are myelinated and innervate the muscles of facial expression and the stapedial muscle. The other 3000 nerve fibers form the nervus intermedius with a secretary and somatosensory component. These include the afferent taste fiber from the chorda tympani nerve, the afferent taste fiber from the soft palate, the parasympathetic secretory innervation to sublingual, submandibular and lacrimal glands, and the cutaneous sensory component from afferent fibers originating from the skin of the auricle and postauricular areas [4]. The brain stem contains the
The anatomy of the facial nerve. Adopted from the free domain:
Knowledge about the normal anatomy, vascular relationship, and the wide spectrum of the abnormalities is vital for the radiologist and neurologist in correctly diagnosing and managing facial nerve disorders.
\nThe pathophysiology of Bell’s palsy remains unclear. Compression of the facial nerve while it course through facial canal, especially the narrow labyrinthine segment, is the most acceptable theory. The compression has been demonstrated in MRI scan with facial nerve enhancement [12]. Any inflammatory, demyelinating, and ischemic or compressive process in this area may impair the neural conduction. Viral infection is the most commonly accepted theory behind Bell’s palsy, and the Herpes simplex virus is the most commonly implicated virus. Other viruses include Mumps virus, cytomegalovirus, and HIV. Other suggested theories include autoimmunity, mycoplasma infection, inflammation, microvascular disease such as diabetes mellitus, and many other mechanisms. It is apparent that none of these theories stands on a solid base.
\nBell’s palsy typically occurs suddenly, and the symptoms peak in less than 48 hours. The paralysis must include the upper and lower aspects of the face, otherwise, if it involves the lower portion of the face, a central cause (supranuclear), such as stroke, should be suspected. If the onset of the facial paralysis is insidious, associated with weakness of the contralateral side, or there is a preceding history of trauma or infection, other causes of facial paralysis must be strongly considered.
\nIn addition to the sudden onset of unilateral upper and lower facial muscle paralysis, the patient may have hyperacusis, posterior auricular pain, otalgia, incomplete eye closure, excessive salivation, and taste disturbances. Many patients report numbness on the affected side. Whether this numbness is due to the involvement of trigeminal nerve or lack of movement of facial muscle is not clear. Ocular pain, epiphora or decreased tearing, and blurred vision are other possible associated symptoms.
\nOn examination, in addition to demonstrate weakness and/or paralysis of the entire side of the face, we find a flattening of the nasolabial fold on the affected side, inability to elevate eyebrow, and distorted face when the patient asked to smile (Figure 2). The patient should be examined in details for full neurological examination, any skin lesion, ear or eye problem, and parotid diseases.
\nSeven-year-old child with left facial palsy asked to smile (published with parent permission).
The goal of treatment of Bell’s palsy is to improve the facial nerve function and to reduce neuronal damage. Steroids (prednisone) and antiviral therapy (acyclovir) are the recommended therapy by the American Academy of Neurology (AAN) and American Academy of Otolaryngology [13]. Additionally, a variety of non-pharmacological therapy is suggested for the treatment of Bell’s palsy including physical therapy (facial exercises, neuromuscular training) and acupuncture. A variety of pharmacological and non-pharmacological treatments to protect the eyes of patient with Bell’s palsy have been used. These include the use of topical ocular lubrication (with artificial tear during the day and lubricating ophthalmic ointment at night), occluding the eyelids by tape or patch, inducing ptosis by botulinum toxins, and many other procedures aiming to protect the patient’s eye from drying, corneal abrasion, and corneal ulcers [14, 15].
\nSurgical treatment of Bell’s palsy with facial nerve decompression is also used, but it still carries a controversy, and it may be considered in patients with poor prognosis as predicted by facial nerve testing (EMG shows greater than 90% axonal degeneration within 3 weeks of the onset of paralysis) or complete persistent paralysis not responding to treatment [16, 17].
\nOther possible causes of facial palsy include congenital facial palsy (Möbius syndrome, hemifacial macrosomia), polyneuritis (Guillain-Barre syndrome, Ramsay-Hunt syndrome due to herpes zoster, autoimmune) malignancy (parotid tumors, brain tumor), trauma (temporal bone fracture, birth injury), sarcoidosis, infections (otitis media, cholesteatoma), and many other rare causes [18].
\nFacial nerve tumors are rare and represent uncommon cause for facial palsy accounting for only 5–10% of all cases of facial nerve palsy [19]. Hearing defects and facial paresis are the most common presenting features. The most commonly identified tumor are schwannomas. Facial nerve schwannomas are benign tumors, which arise from Schwann cells. They mostly occur sporadically; some occur as a part of genetic syndromes as neurofibromatosis types 1 and 2. The facial nerve is the third common site for intracranial schwannomas. The patient usually presents with sudden onset or progressive facial weakness with or without conductive or sensorineural hearing loss, tinnitus, vertigo, facial pain, hemifacial spasm, facial palsy, and otalgia. Workup may involve detailed hearing test, MRI scan of the brain, and CT scan of the temporal bone. Other tumors involving the facial nerve include hemangiomas (accounting for 18% of facial nerve tumors and 0.7% of intratemporal bone tumors) [20], neurofibromas, and meningiomas. Most of these tumors present with facial palsy with or without hearing defects.
\nIt is a segmental myoclonus of muscles innervated by the facial nerve. Gowers first described it in 1884. It affects 11 per 100,000 of the population mostly in the fifth and sixth decade of life with a slight female predominance. The majority of cases are unilateral, although bilateral involvement might occur rarely in severe cases. It generally starts as brief clonic movements of the orbicularis oculi that spread over the years to other facial muscles (corrugator, frontalis, orbicularis oris, platysma, and zygomaticus), and it may become more sustained with time. Although it is a benign condition, it often leads to social embarrassment resulting in psychosocial stress and social withdrawal (Figure 3). HFS is characterized by progressive involuntary clonic or tonic movements of the muscle supplied by the facial nerve. It typically started in the orbicularis oculi muscle and progressively extends to involve the other facial muscle, involving the platysma muscle in severe cases. Most of the cases persist during sleep, and some patients report clicking sound in the ear, which presumed to be due to contraction of the stapedius muscle. In severe cases, impairment of vision might occur because of severe spasm of the orbicularis oculi muscle. The symptoms are usually exaggerated by psychological tension and speech. The main differential diagnosis of HFS includes blepharospasm (occur bilaterally symmetrically), oromandibular dystonia (sustained contraction of the lower part of the face, mouth, mandible and maxilla, tongue and pharynx), facial nerve tic (complex coordinated multifocal movement that switches between the right and left sides of the face), hemimasticatory spasm (painful contractions of the muscles of mastication), focal seizures, and synkinesias after facial nerve paralysis (activation of several muscles innervated by the facial nerve).
\nThe editor of this book is afflicted by right-sided HFS started at the age of 45; unfortunately, vascular decompression failed to resolve the problem. (A) Spasm of the right orbicularis oculi and right facial muscle and (B) spontaneous resolution of the spasm.
The underlying cause of hemifacial spasm in most cases is an ectatic or atypically aberrant blood vessel, which compresses the facial nerve at the place where it exits the brain stem. This area is the most susceptible part of the facial nerve to external stimuli since it ensheathed only by an arachnoidal membrane without the epineurium. Furthermore, this area represents the transition zone between central (oligodendroglial cells) and peripheral (Schwann cells) myelinations, and there is no connective tissue septa that traverse the individual fascicles. In the majority of cases, inferior posterior cerebellar artery or the inferior anterior cerebellar artery is the cause for vascular compression. Rarely, vertebral artery or a combination of these arteries is responsible for this compression. Very rarely, a vein might be the cause. HFS diagnosis is mainly clinically supported by investigations such as electromyography (EMG) and MRI. These investigations are useful also to exclude pathological changes in the cerebellopontine angle such as tumors or brain stem lesions. A high-resolution, T2-weighted sequence is particularly useful in demonstrating vascular compression.
\nThe therapeutic options for HFS are variable ranging from simple applications of heat to pharmacological treatment (carbamazepine, clonazepam, baclofen, and gabapentin) and botulinum injections to microvascular decompression surgery. The response to medications, in general, is poor and not sustained and thus is devoted to milder cases. Botulinum toxin (BOTOX, BTX) became the standard treatment since its use in the early 1980s. It alleviates symptoms in 85–95% of patients. The major drawback is its temporary effects and the need to repeat its administration every 3–4 months [21, 22, 23]. The major advantages of BTX are that it is a noninvasive technique and can be done in an outpatient setting. The only curative therapeutic option is microvascular decompression of the facial nerve by placing a Teflon sponge between the vessel and the brain stem. Using an endoscopic technique makes the operation safe, but still, there is a risk of less than 1% of intraoperative life-threatening complications such as life-threatening hemorrhage or cerebellar or brain stem infarctions. Additionally, postoperative complications including temporary or permanent hearing impairment and permanent facial paralysis may occur in up to 8 and 0.9%, respectively [24].
\nIt is the idiopathic progressive bilateral involuntary spasm of the orbicularis oculi and upper facial muscle (Figure 4). Involvement of the lower face by spasm is not uncommon, and the patient might be functionally blind as the eyes might be closed most of the day. The cause of the blepharospasm is thought to be central, yet the exact mechanism is not known. Treatment options include selective destruction of facial nerve branches that innervate the orbicularis oculi muscle, inducing paralysis of orbicularis oculi muscle by BOTOX, and pharmacological therapy by anticholinergics drug (Artane), benzodiazepine (clonazepam), GABAB receptor agonist (baclofen), anticonvulsant (levetiracetam), and many other drugs [25].
\n(A) Patient with blepharospasm and (B) same patient after treatment.
In addition to a detailed history and clinical examination, investigations are an essential part of the workup of patients with facial nerve disorders. Still, there are controversies about the appropriate investigations that are needed for patients present with facial nerve disorders. The most commonly used investigations include:
\nThese tests used to detect any associated hearing defect and diminished stapedial reflex (paresis of the stapedial branch of the facial nerve). Brain stem auditory evoked response (BAER) in particular is effective in detecting retrocochlear lesion. These tests are not used routinely unless there are multiple cranial nerve palsies [26, 27].
\nFacial paralysis is a recognized feature of leukemia relapses in both children and adult.
\nImaging studies play an important role in the evaluation of facial nerve disorder. MRI is especially helpful in recognizing brain stem pathology, and high-resolution CT scan is helpful in identifying bony abnormalities of the intratemporal facial nerve like congenital anomalies, trauma, and cholesteatoma. MRI is especially helpful in the detection of soft tissue abnormalities around facial nerve as in neoplasms, inflammatory processes, and hemifacial spasm. Recently, facial nerve ultrasound and diffuse tensor tractography (three-dimensional reconstruction of facial nerve using MRI) are used to identify cranial nerve fiber displacement by vestibular schwannomas [28, 29]. Contrast-enhanced MRI is helpful when the facial palsy cannot be definitively localized [30]. The patient’s symptoms and the proposed differential diagnosis will determine the choice between these investigations.
\nNeurophysiological studies are of diagnostic and prognostic value, especially in chronic facial nerve problem. Most of these tests require the cooperation of patients. Examples of these tests include measurement of fibrillation potentials and recording of the blink reflex. The presence of fibrillation potentials, which is part of the electromyography, in the muscles implies the loss of muscle innervation, which indicates a significant axonal degeneration. Blink reflex tests, on the other hand, utilize the polysynaptic nature of this reflex. Trigeminal nerve carries a unilateral stimuli (electric stimulation of the supraorbital nerve or a puff of air on the cornea), producing an early ipsilateral facial motor response followed by a bilateral late response. Absence or delay in the late response can be used to assess facial innervation [31].
\n"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges".
\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.
",metaTitle:"About Open Access",metaDescription:"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges.\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.",metaKeywords:null,canonicalURL:"about-open-access",contentRaw:'[{"type":"htmlEditorComponent","content":"The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\\n\\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\\n\\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
\\n\\n“By “open access” to [peer-reviewed research literature], we mean its free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited” (reference: http://www.budapestopenaccessinitiative.org)
\\n\\nOAI-PMH
\\n\\nAs a firm believer in the wider dissemination of knowledge, IntechOpen supports the Open Access Initiative Protocol for Metadata Harvesting (OAI-PMH Version 2.0). Read more
\\n\\nLicense
\\n\\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
\\n\\nPeer Review Policies
\\n\\nAll scientific works are Peer Reviewed prior to publishing. Read more
\\n\\nOA Publishing Fees
\\n\\nThe Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
\\n\\nDigital Archiving Policy
\\n\\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\\n\\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
\\n\\nOpen Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
\\n\\nOpen Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
\\n\\nWe aim at improving the quality and availability of scholarly communication by promoting and practicing:
\\n\\n\\n"}]'},components:[{type:"htmlEditorComponent",content:'
The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\n\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\n\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
\n\n“By “open access” to [peer-reviewed research literature], we mean its free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited” (reference: http://www.budapestopenaccessinitiative.org)
\n\nOAI-PMH
\n\nAs a firm believer in the wider dissemination of knowledge, IntechOpen supports the Open Access Initiative Protocol for Metadata Harvesting (OAI-PMH Version 2.0). Read more
\n\nLicense
\n\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
\n\nPeer Review Policies
\n\nAll scientific works are Peer Reviewed prior to publishing. Read more
\n\nOA Publishing Fees
\n\nThe Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
\n\nDigital Archiving Policy
\n\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\n\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
\n\nOpen Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
\n\nOpen Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
\n\nWe aim at improving the quality and availability of scholarly communication by promoting and practicing:
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Oncology",slug:"bone-oncology",parent:{id:"190",title:"Oncology",slug:"medicine-oncology"},numberOfBooks:2,numberOfSeries:0,numberOfAuthorsAndEditors:57,numberOfWosCitations:14,numberOfCrossrefCitations:13,numberOfDimensionsCitations:25,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicId:"1074",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"7187",title:"Osteosarcoma",subtitle:"Diagnosis, Mechanisms, and Translational Developments",isOpenForSubmission:!1,hash:"89096359b754beb806eca4c6d8aacaba",slug:"osteosarcoma-diagnosis-mechanisms-and-translational-developments",bookSignature:"Matthew Gregory Cable and Robert Lawrence Randall",coverURL:"https://cdn.intechopen.com/books/images_new/7187.jpg",editedByType:"Edited by",editors:[{id:"265693",title:"Dr.",name:"Matthew Gregory",middleName:null,surname:"Cable",slug:"matthew-gregory-cable",fullName:"Matthew Gregory Cable"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5399",title:"Osteosarcoma",subtitle:"Biology, Behavior and Mechanisms",isOpenForSubmission:!1,hash:"9f1855e3cb1ca5be058bb788243fda7c",slug:"osteosarcoma-biology-behavior-and-mechanisms",bookSignature:"Kanya Honoki and Kurt Richard Weiss",coverURL:"https://cdn.intechopen.com/books/images_new/5399.jpg",editedByType:"Edited by",editors:[{id:"28035",title:"Associate Prof.",name:"Kanya",middleName:null,surname:"Honoki",slug:"kanya-honoki",fullName:"Kanya Honoki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:2,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"54598",doi:"10.5772/67564",title:"Osteosarcoma of the Jaw: Classification, Diagnosis and Treatment",slug:"osteosarcoma-of-the-jaw-classification-diagnosis-and-treatment",totalDownloads:3094,totalCrossrefCites:4,totalDimensionsCites:5,abstract:"Osteosarcomas are rare, highly malignant, bone tumors defined by the presence of malignant mesenchymal cells producing osteoid or immature bone. Osteosarcomas of the jaws are extremely rare, representing about 7% of all osteosarcomas and 1% of all head and neck malignancies. An accurate diagnosis, usually facilitated by chemotherapy (CT), MRI and biopsy, is required in order to define the stage of the disease and plane the adequate treatment. Aggressive surgical resection and advanced technique reconstruction are the mainstay of treatment, as the single most important factor for cure is radical resection. Clinical outcomes can be improved by a multimodal strategy combining surgery with neo-adjuvant and adjuvant chemotherapy in selected cases, and adjuvant radiotherapy in the absence of clear margins.",book:{id:"5399",slug:"osteosarcoma-biology-behavior-and-mechanisms",title:"Osteosarcoma",fullTitle:"Osteosarcoma - Biology, Behavior and Mechanisms"},signatures:"Daris Ferrari, Laura Moneghini, Fabiana Allevi, Gaetano Bulfamante\nand Federico Biglioli",authors:[{id:"188372",title:"Dr.",name:"Daris",middleName:null,surname:"Ferrari",slug:"daris-ferrari",fullName:"Daris Ferrari"},{id:"188884",title:"Dr.",name:"Laura",middleName:null,surname:"Moneghini",slug:"laura-moneghini",fullName:"Laura Moneghini"},{id:"188885",title:"Prof.",name:"Federico",middleName:null,surname:"Biglioli",slug:"federico-biglioli",fullName:"Federico Biglioli"},{id:"194643",title:"Dr.",name:"Fabiana",middleName:null,surname:"Allevi",slug:"fabiana-allevi",fullName:"Fabiana Allevi"},{id:"194645",title:"Prof.",name:"Gaetano",middleName:null,surname:"Bulfamante",slug:"gaetano-bulfamante",fullName:"Gaetano Bulfamante"}]},{id:"54117",doi:"10.5772/67448",title:"Immune Environment and Osteosarcoma",slug:"immune-environment-and-osteosarcoma",totalDownloads:1529,totalCrossrefCites:1,totalDimensionsCites:5,abstract:"Immune niche with its huge cell diversity including more specifically tumour infiltrating lymphocytes (TILs), tumour-associated macrophages (TAMs) regulate osteosarcoma (OS) microenvironment. TAMs exert differential activities in the tumour development according to their polarisation. Indeed, in oncology, M1-polarised macrophages are considered as anti-tumour effectors, and M2-polarised macrophages are defined as pro-tumour modulators by increasing the neoangiogenic process. TAM density is correlated with tumour cell proliferation, invasion, metastasis and poor prognosis in various epithelial and haematological cancers and in bone metastasis. Similarly, tumour infiltrating lymphocytes play a key role in tumour development by inducing a local tolerant environment favourable for the tumour growth. The present chapter will describe the main roles of the immune system in the pathogenesis of osteosarcoma and the most recent therapeutic development based on its regulation.",book:{id:"5399",slug:"osteosarcoma-biology-behavior-and-mechanisms",title:"Osteosarcoma",fullTitle:"Osteosarcoma - Biology, Behavior and Mechanisms"},signatures:"Marie-Françoise Heymann and Dominique Heymann",authors:[{id:"188133",title:"Dr.",name:"Marie-Francoise",middleName:null,surname:"Heymann",slug:"marie-francoise-heymann",fullName:"Marie-Francoise Heymann"},{id:"202635",title:"Prof.",name:"Dominique",middleName:null,surname:"Heymann",slug:"dominique-heymann",fullName:"Dominique Heymann"}]},{id:"53766",doi:"10.5772/67068",title:"Microenvironment Signals and Mechanisms in the Regulation of Osteosarcoma",slug:"microenvironment-signals-and-mechanisms-in-the-regulation-of-osteosarcoma",totalDownloads:1735,totalCrossrefCites:3,totalDimensionsCites:4,abstract:"Osteosarcoma (OS) is the most common malignant primary bone tumor in children and adolescents and features rapid development, strong metastatic ability, and poor prognosis. It has been well established that diverse genetic aberrations and metabolic alterations confer the tumorigenesis and development of OS. The intricate metabolism and vascularization that contributes to the nutrient and structural support for tumor progression should be thoroughly clarified to help us gain novel insights into OS and its clinical diagnoses and treatments. With regard to the complex bone extracellular matrix (ECM) and local cell populations, we intend to illustrate the interrelationship between various microenvironmental signals and the different stages of OS evolution. Solid evidence has noted two crucial factors of the OS microenvironment in the acquisition of stem cell phenotypes - transforming growth factor-β1 (TGF-β1) signaling and hypoxia. Different cell subtypes in the local environment might also serve as unique contributors that interact with each other and communicate with distant cells, thus participating in local invasion and metastasis. Proper models have been established and improved to reveal the evolutionary footsteps of how normal cells transform into a neoplastic state and progress toward malignancy.",book:{id:"5399",slug:"osteosarcoma-biology-behavior-and-mechanisms",title:"Osteosarcoma",fullTitle:"Osteosarcoma - Biology, Behavior and Mechanisms"},signatures:"Yu Zhang, Qing Mai, Xiaowen Zhang, Chunyuan Xie and Yan Zhang",authors:[{id:"151260",title:"Prof.",name:"Zhang",middleName:null,surname:"Yan",slug:"zhang-yan",fullName:"Zhang Yan"},{id:"194516",title:"Ms.",name:"Yu",middleName:null,surname:"Zhang",slug:"yu-zhang",fullName:"Yu Zhang"},{id:"194517",title:"Ms.",name:"Qing",middleName:null,surname:"Mai",slug:"qing-mai",fullName:"Qing Mai"},{id:"199302",title:"Dr.",name:"Xiaowen",middleName:null,surname:"Zhang",slug:"xiaowen-zhang",fullName:"Xiaowen Zhang"},{id:"199303",title:"Dr.",name:"Chunyuan",middleName:null,surname:"Xie",slug:"chunyuan-xie",fullName:"Chunyuan Xie"}]},{id:"67824",doi:"10.5772/intechopen.85190",title:"Differential Diagnosis of Osteogenic Tumors in the Context of Osteosarcoma",slug:"differential-diagnosis-of-osteogenic-tumors-in-the-context-of-osteosarcoma",totalDownloads:1367,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Primary bone tumors are rare, but osteosarcoma (OS) is the fourth commonest non-hematological primary neoplasm of the bone in the adolescence, and the other three commonest neoplasms, in descending order, are leukemia, brain tumors, and lymphoma. The commonest presenting complaints are swelling and aches. These tumors cannot be diagnosed without the help of radiology. There is a wide age range of these neoplasms commonly appearing in the second and third decade of life with a peak incidence in early teens. Males are affected more than females. The exact cause of osteosarcoma is unknown. However, a number of risk factors, like genetic predisposition, some existing bone diseases, environmental risk factors, and radiations, have been identified. If the bone tumors are viewed by clinical, radiological, and histopathological perspectives, the correct diagnosis can be made easily. Chemotherapy combined with surgery is the standard treatment modality with better 5-year survival rates. Elevated AKP is an important prognostic factor in this malignancy.",book:{id:"7187",slug:"osteosarcoma-diagnosis-mechanisms-and-translational-developments",title:"Osteosarcoma",fullTitle:"Osteosarcoma – Diagnosis, Mechanisms, and Translational Developments"},signatures:"Mulazim Hussain Bukhari, Samina Qamar and Farwa Batool",authors:[{id:"266124",title:"Prof.",name:"Mulazim",middleName:"Hussain",surname:"Bukhari",slug:"mulazim-bukhari",fullName:"Mulazim Bukhari"},{id:"272788",title:"Dr.",name:"Farwa",middleName:null,surname:"Batool",slug:"farwa-batool",fullName:"Farwa Batool"},{id:"272790",title:"Dr.",name:"Samina",middleName:null,surname:"Qamar",slug:"samina-qamar",fullName:"Samina Qamar"},{id:"288567",title:"Dr.",name:"Mandeep",middleName:null,surname:"Bedi",slug:"mandeep-bedi",fullName:"Mandeep Bedi"}]},{id:"53758",doi:"10.5772/67070",title:"Osteosarcomagenesis: Biology, Development, Metastasis, and Mechanisms of Pain",slug:"osteosarcomagenesis-biology-development-metastasis-and-mechanisms-of-pain",totalDownloads:1544,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Osteosarcoma is the most common primary cancer of the bone and third most common cancer in children and adolescents with approximately 900 new cases annually in the United States. A major facet of osteosarcoma is its high level of genomic instability, in particular chromosomal instability, which is the result of increased or decreased chromosome number in a cell. Furthermore, pain is the most common symptomatic feature of osteosarcoma that lacks effective therapy. Pain in osteosarcoma is relatively more complicated than many other painful conditions requiring a more thorough understanding of its etiology, pathobiology, and neurobiology to allow the development of better therapies for reducing pain in osteosarcoma patients. Studies are underway to define the diverse modalities of presentation, growth, development, metastases, and nociception in osteosarcoma. New data from human studies in combination with data from studies incorporating transgenic mouse models of osteosarcoma are providing valuable insights into the mechanisms underlying the development of both the tumor and the tumor-induced pain. These new data will undoubtedly lead to improved prognoses, as well as the development of novel therapeutics that will significantly decrease bone cancer pain.",book:{id:"5399",slug:"osteosarcoma-biology-behavior-and-mechanisms",title:"Osteosarcoma",fullTitle:"Osteosarcoma - Biology, Behavior and Mechanisms"},signatures:"Branden A. Smeester, Branden S. Moriarity and Alvin J. Beitz",authors:[{id:"187313",title:"Prof.",name:"Alvin J",middleName:null,surname:"Beitz",slug:"alvin-j-beitz",fullName:"Alvin J Beitz"},{id:"187983",title:"Ph.D. Student",name:"Branden",middleName:null,surname:"Smeester",slug:"branden-smeester",fullName:"Branden Smeester"},{id:"194521",title:"Prof.",name:"Branden",middleName:null,surname:"Moriarity",slug:"branden-moriarity",fullName:"Branden Moriarity"}]}],mostDownloadedChaptersLast30Days:[{id:"53932",title:"A Dog in the Cancer Fight: Comparative Oncology in Osteosarcoma",slug:"a-dog-in-the-cancer-fight-comparative-oncology-in-osteosarcoma",totalDownloads:4598,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Since the great Rudolf Virchow advised, “Between animal and human medicine there is no dividing line, nor should there be,” limited attention has been paid to cancer in animals. This is finally changing thanks to a renewed focus on studying pet dogs with cancer. Unlike the laboratory mice who have been the mainstay of animal models of disease, pet dogs share an environment with their human owners, have an intact immune system, and often develop diseases spontaneously in ways that mimic their human counterparts. Osteosarcoma (OSA) – while uncommon in humans - is a common malignancy in dogs. This comparatively high incidence alone renders pet dogs an ideal “model” to conduct translational and clinical research into OSA. Indeed, there are many similarities between the two species with respect to this disease. However, owing to the shorter life span and accelerated disease progression, treatment effects can be assessed much more rapidly in canines than in humans. Overall, dogs represent a unique model to study OSA; this chapter aims to discuss the ways that comparative oncology between dogs and humans are being used from basic science research, to genetics and mechanisms of disease, to tumor biology and finally to developing novel treatments.",book:{id:"5399",slug:"osteosarcoma-biology-behavior-and-mechanisms",title:"Osteosarcoma",fullTitle:"Osteosarcoma - Biology, Behavior and Mechanisms"},signatures:"Alexander L. Lazarides, Allison B. Putterman, William C. Eward and\nCindy Eward",authors:[{id:"189065",title:"Dr.",name:"Alexander",middleName:"Leandros",surname:"Lazarides",slug:"alexander-lazarides",fullName:"Alexander Lazarides"},{id:"189071",title:"Dr.",name:"William",middleName:null,surname:"Eward",slug:"william-eward",fullName:"William Eward"},{id:"189072",title:"Dr.",name:"Allison",middleName:"Brooke",surname:"Putterman",slug:"allison-putterman",fullName:"Allison Putterman"},{id:"196706",title:"Dr.",name:"Cindy A.",middleName:null,surname:"Eward",slug:"cindy-a.-eward",fullName:"Cindy A. Eward"}]},{id:"54268",title:"Biological Reconstruction Using Liquid Nitrogen-Treated Tumor Bearing Bone",slug:"biological-reconstruction-using-liquid-nitrogen-treated-tumor-bearing-bone",totalDownloads:1593,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"In general, a tumor prosthesis is used for reconstruction after removal of osteosarcoma. However, the durability of artificial materials becomes a problem in the long term, and many patients inevitably undergo revision due to loose or damaged prostheses. Moreover, preservation of articular surface is the key to maintain better limb function for long duration. Reconstruction of affected limbs using biological materials has been sought to overcome the aforementioned problems. In some countries, it is significantly difficult to obtain allograft as a biological reconstruction material because of socio-religious or cost problem. Thus, a biological reconstruction method has been developed in which the patient’s affected bone is treated and used for reconstruction. Especially in recycling treatment for affected autologous bone, liquid nitrogen treatment has several favorable characteristics. There is optimal morphological fit because the treated bone itself is one’s own, and bone strength is maintained after treatment. Satisfactory bone union and bone regeneration are expected to be achieved due to good osteoconduction and osteoinduction because proteins and enzymes are preserved in the bone.",book:{id:"5399",slug:"osteosarcoma-biology-behavior-and-mechanisms",title:"Osteosarcoma",fullTitle:"Osteosarcoma - Biology, Behavior and Mechanisms"},signatures:"Norio Yamamoto and Hiroyuki Tsuchiya",authors:[{id:"189049",title:"Prof.",name:"Norio",middleName:null,surname:"Yamamoto",slug:"norio-yamamoto",fullName:"Norio Yamamoto"},{id:"202742",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Tsuchiya",slug:"hiroyuki-tsuchiya",fullName:"Hiroyuki Tsuchiya"}]},{id:"54598",title:"Osteosarcoma of the Jaw: Classification, Diagnosis and Treatment",slug:"osteosarcoma-of-the-jaw-classification-diagnosis-and-treatment",totalDownloads:3094,totalCrossrefCites:4,totalDimensionsCites:5,abstract:"Osteosarcomas are rare, highly malignant, bone tumors defined by the presence of malignant mesenchymal cells producing osteoid or immature bone. Osteosarcomas of the jaws are extremely rare, representing about 7% of all osteosarcomas and 1% of all head and neck malignancies. An accurate diagnosis, usually facilitated by chemotherapy (CT), MRI and biopsy, is required in order to define the stage of the disease and plane the adequate treatment. Aggressive surgical resection and advanced technique reconstruction are the mainstay of treatment, as the single most important factor for cure is radical resection. Clinical outcomes can be improved by a multimodal strategy combining surgery with neo-adjuvant and adjuvant chemotherapy in selected cases, and adjuvant radiotherapy in the absence of clear margins.",book:{id:"5399",slug:"osteosarcoma-biology-behavior-and-mechanisms",title:"Osteosarcoma",fullTitle:"Osteosarcoma - Biology, Behavior and Mechanisms"},signatures:"Daris Ferrari, Laura Moneghini, Fabiana Allevi, Gaetano Bulfamante\nand Federico Biglioli",authors:[{id:"188372",title:"Dr.",name:"Daris",middleName:null,surname:"Ferrari",slug:"daris-ferrari",fullName:"Daris Ferrari"},{id:"188884",title:"Dr.",name:"Laura",middleName:null,surname:"Moneghini",slug:"laura-moneghini",fullName:"Laura Moneghini"},{id:"188885",title:"Prof.",name:"Federico",middleName:null,surname:"Biglioli",slug:"federico-biglioli",fullName:"Federico Biglioli"},{id:"194643",title:"Dr.",name:"Fabiana",middleName:null,surname:"Allevi",slug:"fabiana-allevi",fullName:"Fabiana Allevi"},{id:"194645",title:"Prof.",name:"Gaetano",middleName:null,surname:"Bulfamante",slug:"gaetano-bulfamante",fullName:"Gaetano Bulfamante"}]},{id:"53758",title:"Osteosarcomagenesis: Biology, Development, Metastasis, and Mechanisms of Pain",slug:"osteosarcomagenesis-biology-development-metastasis-and-mechanisms-of-pain",totalDownloads:1544,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Osteosarcoma is the most common primary cancer of the bone and third most common cancer in children and adolescents with approximately 900 new cases annually in the United States. A major facet of osteosarcoma is its high level of genomic instability, in particular chromosomal instability, which is the result of increased or decreased chromosome number in a cell. Furthermore, pain is the most common symptomatic feature of osteosarcoma that lacks effective therapy. Pain in osteosarcoma is relatively more complicated than many other painful conditions requiring a more thorough understanding of its etiology, pathobiology, and neurobiology to allow the development of better therapies for reducing pain in osteosarcoma patients. Studies are underway to define the diverse modalities of presentation, growth, development, metastases, and nociception in osteosarcoma. New data from human studies in combination with data from studies incorporating transgenic mouse models of osteosarcoma are providing valuable insights into the mechanisms underlying the development of both the tumor and the tumor-induced pain. These new data will undoubtedly lead to improved prognoses, as well as the development of novel therapeutics that will significantly decrease bone cancer pain.",book:{id:"5399",slug:"osteosarcoma-biology-behavior-and-mechanisms",title:"Osteosarcoma",fullTitle:"Osteosarcoma - Biology, Behavior and Mechanisms"},signatures:"Branden A. Smeester, Branden S. Moriarity and Alvin J. Beitz",authors:[{id:"187313",title:"Prof.",name:"Alvin J",middleName:null,surname:"Beitz",slug:"alvin-j-beitz",fullName:"Alvin J Beitz"},{id:"187983",title:"Ph.D. Student",name:"Branden",middleName:null,surname:"Smeester",slug:"branden-smeester",fullName:"Branden Smeester"},{id:"194521",title:"Prof.",name:"Branden",middleName:null,surname:"Moriarity",slug:"branden-moriarity",fullName:"Branden Moriarity"}]},{id:"67824",title:"Differential Diagnosis of Osteogenic Tumors in the Context of Osteosarcoma",slug:"differential-diagnosis-of-osteogenic-tumors-in-the-context-of-osteosarcoma",totalDownloads:1367,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Primary bone tumors are rare, but osteosarcoma (OS) is the fourth commonest non-hematological primary neoplasm of the bone in the adolescence, and the other three commonest neoplasms, in descending order, are leukemia, brain tumors, and lymphoma. The commonest presenting complaints are swelling and aches. These tumors cannot be diagnosed without the help of radiology. There is a wide age range of these neoplasms commonly appearing in the second and third decade of life with a peak incidence in early teens. Males are affected more than females. The exact cause of osteosarcoma is unknown. However, a number of risk factors, like genetic predisposition, some existing bone diseases, environmental risk factors, and radiations, have been identified. If the bone tumors are viewed by clinical, radiological, and histopathological perspectives, the correct diagnosis can be made easily. Chemotherapy combined with surgery is the standard treatment modality with better 5-year survival rates. Elevated AKP is an important prognostic factor in this malignancy.",book:{id:"7187",slug:"osteosarcoma-diagnosis-mechanisms-and-translational-developments",title:"Osteosarcoma",fullTitle:"Osteosarcoma – Diagnosis, Mechanisms, and Translational Developments"},signatures:"Mulazim Hussain Bukhari, Samina Qamar and Farwa Batool",authors:[{id:"266124",title:"Prof.",name:"Mulazim",middleName:"Hussain",surname:"Bukhari",slug:"mulazim-bukhari",fullName:"Mulazim Bukhari"},{id:"272788",title:"Dr.",name:"Farwa",middleName:null,surname:"Batool",slug:"farwa-batool",fullName:"Farwa Batool"},{id:"272790",title:"Dr.",name:"Samina",middleName:null,surname:"Qamar",slug:"samina-qamar",fullName:"Samina Qamar"},{id:"288567",title:"Dr.",name:"Mandeep",middleName:null,surname:"Bedi",slug:"mandeep-bedi",fullName:"Mandeep Bedi"}]}],onlineFirstChaptersFilter:{topicId:"1074",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:99,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:288,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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"}}}}]},series:{item:{id:"25",title:"Environmental Sciences",doi:"10.5772/intechopen.100362",issn:"2754-6713",scope:"
\r\n\tScientists have long researched to understand the environment and man’s place in it. The search for this knowledge grows in importance as rapid increases in population and economic development intensify humans’ stresses on ecosystems. Fortunately, rapid increases in multiple scientific areas are advancing our understanding of environmental sciences. Breakthroughs in computing, molecular biology, ecology, and sustainability science are enhancing our ability to utilize environmental sciences to address real-world problems.
\r\n\tThe four topics of this book series - Pollution; Environmental Resilience and Management; Ecosystems and Biodiversity; and Water Science - will address important areas of advancement in the environmental sciences. They will represent an excellent initial grouping of published works on these critical topics.