- Transmission of information or data, when it is essential for an amount of energy to reach the receiver to restore the transmitted information;\n
- Transmission of electric energy in the form of electromagnetic field, when the energy transfer efficiency is essential, the power being used to energize the receiving equipment.\n
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In recent years, the advent of evidence-based medicine has led to the publication of several studies on Manual Therapy, thereby enabling a better understanding of the mechanisms underlying its effectiveness in clinical settings. However, this method originated in ancient times. Indeed, testimonies show that it was applied in very distant times and places and in very different forms, contexts, and cultures, such as by shamans in Central Asia and bone setters in Mexico, Nepal, Russia, and Norway [1]. We have direct evidence by Hippocrates (ca. 400 BC) who described the use of manipulative and physical therapy for the treatment of scoliosis and vertebral dysfunctions. Similar techniques were described by Galen, a roman surgeon (ca. 150 CE), and illustrated in his treatises [2].
\nIn the Western world, modern Manual Therapy dates back to the seventeenth century and has undergone a progressive evolution that has led to current manual practices in physiotherapy, osteopathy, and chiropractic [1].
\nMost of the current clinical practice and manual techniques used by the majority of practitioners defined as “experts in manipulative treatments,” are based on biomechanical assumptions at the root of the patient’s symptoms, with palpatorily identifiable dysfunctions, that can be treated by means of specific techniques aimed at joint tissue [3, 4, 5], myofascial tissue [6, 7, 8], or nervous tissue [9].
\nAll these concepts, based on anatomical theoretical models of musculoskeletal and health disorders, were born and developed as a result of the often brilliant intuitions of different authors, but they must be interpreted within the context in which they were born, the knowledge, the cultural contexts, and the technological and instrumental options available at the time [2].
\nEach author has, in some way, enabled the development of our approach to the patient and their management: witness symptom modification (Mulligan Concept) [4], the role of self-treatment (McKenzie Method) [3], and the need to focus clinical practice on the patient’s daily demands and difficulties (Maitland Approach) [10].
\nHowever, the biomechanical effects and elements at the basis of the effectiveness of these approaches have been increasingly challenged by the advent of an evidence-based medicine culture [11]. Although expert opinion is part of the evidence pyramid that should guide clinical practice, it is only the lowest level of evidence [12].
\nStudies published in the last 30 years have seriously challenged both the “tissue-related” and “biomechanical” bases of these manual approaches and the validity and reliability of the techniques involving palpatory assessment as well as manual and manipulative treatment [13, 14, 15].
\nAs healthcare professionals, we have a duty to ask ourselves questions: “Are we really able to accurately palpate a specific target tissue from an assessment point of view? [16] Are we able to identify a specific tissue as responsible for the patient’s symptoms? Are we able to differentiate it from the surrounding tissues and identify any dysfunctions? [14, 17]”.
\nFrom a therapeutic point of view, are we able to make structural changes to peripheral tissues, whether they consist in joint repositioning or orientation of collagen fibers in the myofascial tissue?
\nAbove all, is the modification of peripheral tissues related, and therefore necessary, to the achievement of clinical improvements in patients experiencing musculoskeletal pain?
\nHow important are these factors in changing the prognosis of musculoskeletal patients? How much must a manual technique and a healthcare professional be “biomechanically specialized” to achieve a positive outcome in the patient? Highlighting these elements is extremely important, as they are still the basis of the clinical practice, care, and treatment of millions of patients worldwide and thus have a major clinical impact [18]. What technique or approach can improve the symptoms of patients with musculoskeletal pain, and why?
\nToday, there is a wealth of literature supporting the effectiveness of Manual Therapy in improving pain and mobility in patients with musculoskeletal disorders [19, 20, 21]. However, these improvements are mainly short-term and have a reduced efficacy, particularly in subjects with chronic symptoms [21].
\nThe limited efficacy in patients with chronic pain and the overlapping course of clinical symptoms in the long term irrespective of manual treatments [22, 23] cast doubt on the clinical assumptions that still often guide manual and manipulative clinical practice.
\nThe lack of a shared model supported by evidence and the limited diagnostic, therapeutic, and prognostic role of approaches linked to exclusively manual and biomechanical interventions has led to the development and implementation of what has been defined as the biopsychosocial model, also in the field of rehabilitation [24].
\nThe biopsychosocial model is currently the reference model when it comes to taking care of and managing patients with musculoskeletal disorders. It focuses on the patient as a person, particularly with regard to disability and quality of life in relation to their disorder, considering the impact that internal and external factors, including non-biomechanical ones, can have on their status and prognosis [20, 25].
\nEnter psychosocial factors. Elements such as fear of movement, anxiety, depression, and self-efficacy have been shown to play a central role in mediating and modulating the symptoms and prognosis of these patients [25], particularly in the transition from the acute to the chronic phase of the disorder and the resulting disability [26, 27], far more than exclusively biomechanical impairments such as range of movement (ROM) or muscle strength [28].
\nWhile a manual clinical practice based on musculoskeletal impairments and aimed at improving the patient’s signs and symptoms may be useful and reasonable in the clinical management of the patient [19], it is important to consider that any therapeutic intervention is directed towards a person, with both explicit and implicit consequences on the individual’s beliefs, convictions, and cognitive processes [29].
\nIndeed, while a manual technique can be effective in the short term, the narrative that guides it, which the practitioner presents when framing the patient and taking care of them, can have very significant consequences on the meaning that the patient gives and will give to their own disorder [30].
\nTo date, several authors have linked pain to the body’s perception of a threat/danger [31]. A manipulative technique that is effective in reducing a patient’s lumbar pain may have significant long-term consequences if associated with concepts related to a “repositioning” of the intervertebral disc with respect to the nerve roots. The patient will indeed be able to convince themselves that they have a fragile back, with structures that could face possible neurological damage, thereby promoting hypervigilance, anxiety, and fear of movement [32].
\nIn addition to short-term beneficial effects, it is therefore important to consider possible “nocebo” effects of Manual Therapy in the long term when not properly presented to the patient [32]. It is no coincidence that manual techniques have shown insignificant results in the long run, even when compared with nontreatment. However, if we want to change the patient’s prognosis, we need to act on the most significant prognostic factors, which have been shown to be psychosocial [33].
\nAll of this has an impact not only on the individual but also on the community. This is particularly the case at a time when the availability of economic resources for supporting healthcare and personal health services is constantly subject to spending review. As a matter of fact, we know that most of the resources are allocated to the treatment of chronic disorders.
\nThe effectiveness and efficiency of health decision-making processes and the appropriateness of the therapies proposed and supported are and will increasingly be central to social choices [34]. However, these same considerations apply to every single practitioner, even in the private sector. From an ethical standpoint, what are the best therapies that can be offered to patients with musculoskeletal disorders? Which patients need complex therapies, and when can unimodal therapies achieve satisfactory clinical results? Is there an evidence-based approach to Manual Therapy that can allow for its full integration within a biopsychosocial model focused on the improvement of the patient’s disability not only in the short term but also in the medium and long term? Can the patient be involved in these issues, even if mainly passive techniques are used? At the end of the day, what is Manual Therapy? What does it do, and why can it be so decisive in some cases for both the patient and the practitioner? We will try to answer all these questions in this chapter.
\nEven today, most Manual Therapy approaches are based on the evaluation of biomechanical factors that may be the cause or consequence of symptoms reported by the patient, with a feeling of pain and reduction in function, either directly at the local and segmental level or indirectly in neighboring regions [35].
\nThe basic assumption entails the possibility, on the part of the healthcare worker, to be able to identify the said dysfunctions, correlate them to the clinical picture of the patient, and correct them by the use of palpatory analyses and therapeutic techniques that can be refined over years of practice, thereby making the rehabilitation process increasingly efficient and effective. In general terms, these elements are transversally present in almost all of the most commonly suggested and used Manual Therapy methods, especially in the direct approaches to the assessment and treatment of myofascial and articular tissues [8, 36].
\nBeing able to fully understand and judge the scientific nature and validity of the proposed notions can be complex, especially at the beginning of one’s personal and professional training, especially when presented by charismatic teachers with years of experience. Moreover, at first, the disciple can often find it difficult to manually perceive the biomechanical impairments the teacher refers to.
\nOne may intuitively think that, as with any learning process, palpation skills can be developed and learned through training, repetition, and clinical practice, as it has been observed in the improvement in in the two-point discrimination threshold [36]. But is this really the case from a clinical point of view? How much can daily clinical practice improve one’s palpatory ability, with consequent clinical repercussions in the treatment of patients with musculoskeletal pain? And how much of this progressive understanding of and expertise in patient management depends on effective manual specialization?
\nThe above example may be familiar to many of those who are reading this chapter. However, many of the theoretical assumptions upon which these models are based were wrong. Indeed, the manual assessment methods adopted in most manipulative approaches have not shown adequate levels of validity and reliability for application in the management of patients with musculoskeletal pain.
\nFor instance, techniques for the assessment of the physiological intervertebral motion of individual vertebral levels have not shown a correlation with the actual mobility assessed by means of radiological tests [37]. As a matter of fact, vertebral levels deemed hypomobile upon manual assessment have not shown a reduction in mobility when investigated through dynamic MRI [38].
\nMoreover, the same possibility of investigating the passive physiological and accessory mobility of a single vertebral level by means of manual assessments has been heavily criticized. Indeed, the proposed techniques have been shown to produce movements on multiple vertebral levels [17, 39]. The same assessments, even when made by experienced clinicians, have not shown a correlation with the patient’s symptoms. Indeed, the assessors were not able to tell subjects with pain from an asymptomatic control group [40].
\nThe same palpatory identification of the target structures proved to be poorly reproducible, with little agreement also as to the identification and pinpointing of anatomically evident elements such as the posterior superior and anterior superior iliac spines [30]. It is therefore not surprising that the assessment of any hypomobility or hypermobility of the selected segments shows low agreement values among different assessors [41, 42] and that different therapists choose treat different joints [43].
\nThis seems to be related to the technique used and the actual total mobility of the considered joints [44]. As a matter of fact, it appears to be good in the assessment of the osteokinematic mobility of large joints [45], but it is almost useless or comparable to random chance in the assessment of joints with particularly limited mobility, such as sacroiliac joints [46]. Therefore, the more emphasized the role of specialized manual skills in identifying possible dysfunctions, the more statistically insignificant the results of these tests, even when conducted by experienced clinicians [47].
\nSimilar analyses have been performed as to the palpatory assessment of extra-articular soft tissues, thereby showing that even very experienced assessors are hardly able to identify the anatomical location of the target tissues [48], grade the muscle stiffness [49], pinpoint any tissue dysfunction, or tell a subject with pain from a healthy one. In some cases, even the creators of some of the methods proved inadequate [50].
\nTherefore, while different training proposals involving Manual Therapy may initially seem logical, intuitive, and fascinating, their biomechanical and tissue-related bases have often proven to be incorrect, for instance, by failing to consider the very high prevalence of bone asymmetries in 85% of the general population [51, 52].
\nThe phenomenon defined as “pareidolia” seems to play a significant role when it comes to the lack of accuracy of these theoretical models, which were conceived in, and are therefore inevitably related to, historical periods in which the available technologies did not allow for a thorough understanding of the body and its biomechanical properties. Pareidolia [53] is the tendency to detect patterns and information known to the observer on the basis of random, vague, and undefined inputs, hence the tendency to pinpoint an alteration or a dysfunction exclusively on the basis of one’s own personal experience, be it training-related or not.
\nHowever, several cognitive biases can affect the reasoning and clinical practice of a healthcare professional, particularly in Manual Therapy [54, 55, 56]: witness anchoring, confirmation, group biases, or the illusion of frequency. A group bias is the tendency to overestimate and deem more competent those who belong to one’s group, such as a teacher or a colleague who uses our same assessment and treatment method, compared to other professionals. A similar mechanism is found in frequency bias, based on which we tend to detect factors and elements more easily once we have spent time studying them in depth: witness the possibility of finding an increased prevalence of positional or tissue alterations in our patients following a course focused on these aspects, regardless of their clinical significance. Anchoring bias highlights the tendency to focus on relatively unimportant aspects, thereby attaching central significance to them in the overall picture. In clinical practice, witness the tendency to focus on the restoration of ideal soft tissue consistency, thereby either underestimating or not considering the lack of improvement in the pain perceived by the patient during the rehabilitation process. On the other hand, confirmation bias refers to the tendency to irrationally focus on the first clinical hypothesis that one may have developed with regard to a specific patient and clinically research elements that confirm the said hypothesis, thereby discarding any significant aspects that would invalidate it [54, 55, 56]. All of these elements can be related to heuristics [55], that is, mental shortcuts that enable you to obtain quick answers even without considering all the factors involved. While such aspects allow for faster and more efficient reasoning, in clinical practice they can also lead to errors in the decision-making process and to a nonoptimal management of the patient and thus to an incorrect reading of clinical phenomena [57]. Such observations are obviously not only part of Manual Therapy but also of rehabilitation approaches based on therapeutic exercise [58], which, when proposed in an orthodox manner, can lead to a “guru-based” clinical practice in which the core of the rehabilitation process is no longer the patient, but the method or mental scheme of the practitioner themselves.
\nTherefore, an ethical model of patient treatment and care cannot be separated from a thorough understanding of the scientific literature, in which many of the aspects described above have been studied and deepened, thereby giving answers to many of the questions that may arise during daily clinical practice [34]. Only in this way is it possible to have a clinical practice that can improve the medium- and long-term prognosis of patients with musculoskeletal disorders, thereby reducing the negative influence of cognitive bias and theoretical models.
\nBuilding upon the said assumptions, it is indeed possible to strongly support the effectiveness of Manual Therapy in the improvement of various impairments that characterize the clinical pictures of patients with musculoskeletal disorders, especially with respect to pain and range of movement and with particular reference to the short and medium term, with a high level of satisfaction on the part of the patients who receive it [19, 20].
\nHowever, the mechanisms underlying its effectiveness seem different from those considered up to now. As a matter of fact, the clinical improvement observed as a result of manual techniques does not appear to be related to a realignment of the articular heads [59], a displacement of the disc tissue [60], or a structural modification of the soft tissues [61], which to date have never been demonstrated, despite years of scientific research [60]. Fortunately, these changes do not appear to be necessary in order to achieve a significant therapeutic effect, nor do they appear to be related to the clinical picture of patients with musculoskeletal pain [62].
\nIndeed, models based on biomedical and biomechanical assumptions have been shown to play a clinical role mostly in strictly pathoanatomical pictures and in relation to particularly significant structural alterations such as the presence of severe osteoarthritis, which are related to significant alterations in the articular surfaces where the pathognomonic data shows a marked reduction in joint ROM [63].
\nNevertheless, these elements have been shown to have limited clinical or scientific value in the management of most musculoskeletal disorders. As a matter of fact, verifiable modifications observed in radiological investigations were present in a large part of the general population, without showing, in the great majority of cases, a significant correlation with the clinical picture reported by the patient [64]. This has been observed in clinical pictures related to the axial skeleton but also to the limbs: witness patellofemoral pain syndrome [65] or shoulder pain [66]. Indeed, most patients with musculoskeletal pain have multifactorial disorders. The attempt to translate the determinism typical of the biomedical model and orthopedic medicine into musculoskeletal rehabilitation is probably at the root of the limitations of many Manual Therapy methods, which show resistance to change in the face of the latest scientific findings in the field of Manual Therapy and musculoskeletal pain.
\nUncertainty management in medicine is one of the most debated issues in healthcare-related clinical reasoning and can be disorienting and complex to integrate into one’s vision and clinical practice [67]. However, once accepted, it enables one to confidently respond to various criticalities that may arise on a daily basis: witness patients who do not adequately respond to therapies despite the correct manipulation of specific target segments or still show symptoms despite a palpatory analysis that is normalized with respect to the initially identified dysfunctions.
\nThe very multifactorial nature of these disorders requires multifactorial treatments also involving peripheral tissues, for example, manual techniques, which can allow for significant improvements with respect to symptoms and thus in the quality of life of the patient, regardless of the search for actual anatomical changes. Fortunately, these changes, as mentioned, do not seem to be necessary [60]. Manual Therapy can be extremely effective in reducing pain and improving ROM in these patients. Its effects seem to be mainly mediated by neurophysiological mechanisms [68].
\nSeveral studies have described the mechanical stimulus applied through Manual Therapy techniques as able to activate a cascade of peripheral, spinal, and supraspinal neurophysiological effects related to pain modulation and ROM improvement [68]. For example, as a result of joint tissue techniques, a reduction in the concentration of inflammation mediators was observed [68]. The role of spinal mechanisms was suggested by the change in temporal summation and muscle tone [69]. Finally, studies conducted using functional magnetic resonance imaging have shown the activation of areas related to mechanisms leading to a downward modulation of pain, such as the periaqueductal gray [69]. These scientifically proven observations thus seem to establish a very significant correlation between the clinical efficacy of Manual Therapy and the possibility of activating neurophysiological mechanisms linked to the modulation of pain perception. This seems to be confirmed by studies that have shown an inability to produce therapeutic effects in subjects with alterations of the said mechanisms, that is, in the presence of augmented temporal summation, which is indicative of increased dorsal horn excitability, or of a clinical state of widespread pain with a generalized reduced pressure pain threshold, which is indicative of the presence of central sensitization with regard to pain [69].
\nHowever, there are other aspects of Manual Therapy that are not closely linked to the mechanical stimulation of the technique used and can mediate its therapeutic effect. The said aspects are an integral part of the biopsychosocial model. As a matter fact, there is an affective and cognitive dimension that involves the patient in the therapeutic act linked to the therapeutic “touch” [70]. In accordance with the gate theory, in addition to a reduction of pain perception due to tactile stimulation, touch applied in an “empathic” way has proven capable of reducing pain perception in itself and acting on the concentration of biomarkers related to stress, negative emotions, and mechanisms related to the perception of threats. Furthermore, several contextual and verbal communication and relationship aspects have been shown to play a role in making a manual technique effective with regard to pain reduction. An open, positive, and empathetic style of communication adopted by a healthcare professional capable of listening to the patient and convincingly answering their questions has indeed been associated with greater short-term pain reduction and higher patient satisfaction [71]. The same can be said for the patient’s possible preferences, which may be related to previous experiences or personal beliefs. All these effects are attributable to what has been defined as “placebo mechanisms,” not intended as a psychological response to inert therapies, but as generalized and non-specific “psychologically and physiologically active process associated with a robust hypoalgesic response” [72, 73]. Finally, psychosocial factors such as anxiety and fear of movement or motion (kinesiophobia) and self-efficacy seem to play a very important role when it comes to the effectiveness of a given technique or approach [74].
\nAll these observations show that, irrespective of the criticism levelled at the most commonly proposed clinical models, a scientific approach focused on the patient, based on Manual Therapy and founded on the biopsychosocial model, is possible without the need to resort to imaginative holistic or pseudoscientific theories.
\nThe second part of this chapter will show when and how it is possible to adopt the said approach in the most common clinical pictures that can be dealt with in clinical practice.
\nAs described, Manual Therapy techniques targeting joint or extra-articular soft tissue can be very effective in relieving pain and improving ROM in individuals with musculoskeletal disorders, both in the spine and in the limbs [21].
\nJoint techniques can be divided into mobilization and manipulation techniques [75]. Joint mobilization has been defined as “a Manual Therapy technique comprising a continuum of skilled passive movements involving the joint complex that are applied at varying speeds and amplitudes, which may include a small-amplitude/high velocity therapeutic movement [manipulation] with the intent to restore optimal motion and function and/or reduce pain.” Joint manipulations have been defined as “passive, high velocity, low amplitude thrusts applied to a joint complex within its anatomical limit with the intent to restore optimal motion and function and/or reduce pain” [75].
\nIn studies conducted on standardized populations of subjects with musculoskeletal pain, no manual technique could be shown to be more effective than the other. Research has shown an overlap in the therapeutic effectiveness of different techniques, be it among different types of joint mobilization techniques [76, 77] and different kinds of vertebral manipulation techniques [78] or mobilization and manipulation techniques [79]. These results have been mainly observed in non-specific spinal pain but also when comparing different techniques targeted towards peripheral joints, that is, in subjects with knee osteoarthritis [80]. Similarly, research comparing joint techniques with soft tissue techniques has shown similar clinical results [81, 82].
\nSeveral manual techniques have been proposed for the treatment of soft tissues, from more intense manual approaches following methods that seek the elicitation of significant pain in the patient during their application [8] to painless techniques seeking the elimination of symptoms by using positionings and maneuvers primarily aimed at shortening the tissues [83].
\nAgain, manual techniques have been shown to alleviate pain and improve ROM [84]. Likewise, no one technique can be said to be superior to another, either among different Manual Therapy techniques or between manual techniques and the use of instruments such as dry needling or instrument-assisted soft tissue manipulation (IASTM) [84, 85].
\nAccording to most Manual Therapy methods, the likelihood of therapeutic success in patients with spinal pain strictly depends on the identification of the dysfunctional vertebral level; the appropriate “corrective” technique, which is to be targeted towards the intended segment using the correct parameters of direction, is thus to be applied with the correct direction, intensity, and duration parameters with respect to the stimulus [10].
\nHowever, the need for specific therapeutic techniques is not supported by the literature. As already seen in this chapter, manual and palpatory assessment methods have been found to be ineffective and unreliable. Experienced assessors taking part in a blind study showed agreement levels equal, if not inferior, to random chance in the identification of the tissues to be treated [43]. These same models did not prove valid even with regard to the proposed therapeutic techniques. Indeed, sacroiliac [15], lumbar [15, 86], thoracic [86], and cervical [87] manipulation techniques have been shown to produce clinical and biomechanical effects on different vertebral levels, which are therefore not specific to the target segment and lead the practitioner to produce unpredictable vertebral movements [88]. This data is confirmed by clinical studies that have shown an overlap between the therapeutic effect of manipulations theoretically directed at a single vertebral level and “global” manipulation techniques involving the lumbar spine of subjects with low back pain [89].
\nNevertheless, in clinical practice, very different clinical responses are commonly observed in different patients as a result of the application of the same technique. In the last 20 years, several studies have tried to identify the clinical elements present at the baseline that could indicate the best therapeutic solution for each specific patient [90]. In particular, the so-called clinical prediction rules (CPRs) [91] have been studied and developed for the issues referred to in this chapter, also with reference to manipulative treatment in patients with lumbar [92], cervical [93], and shoulder pain [94], among others. Despite promising initial studies, these rules have not proven to be good enough for application in clinical practice. In particular, evidence has shown that, upon modification of the statistical value considered as the indicator of “therapeutic success” [whether it be pain reduction or improvement of the disability, either in proportional or absolute terms], these rules also change in a very significant way [95]. In addition, subjects positively responding to CPRs with respect to lumbar manipulative treatment were found to be equally responsive to joint mobilization techniques [96] and McKenzie exercises [97]. In essence, a positive response to these rules proved able to generally predict a positive prognosis following a rehabilitation program, regardless of the proposed therapy [98].
\nThe presence of similar therapeutic effectiveness following treatment approaches that are sometimes in direct opposition to each other [8, 83] both in their theoretical bases and in their clinical application is a further element supporting the poor biomechanical validity of these techniques and the predominant role of neurophysiological factors in their effectiveness. Neurophysiological elements have proven to be fundamental in determining the clinical picture of the patient and mediating the effectiveness of techniques targeting peripheral tissues [68].
\nAs a matter of fact, Manual Therapy has been shown to be more effective in the presence of mechanical pain, which is by definition elicited during the execution of specific movements and refers to clinical pictures of peripheral nociceptive pain [69]. Clinically speaking, this kind of pain is a typical feature of patients experiencing sudden problems, such as subjects with acute lumbar block following a poorly controlled movement. On the contrary, patients with constant, general pain present even at rest, which is indicative of central sensitization, have shown little response to manual treatments [69]. This aspect seems to play an important role with regard to the low effectiveness of manual techniques in subjects with chronic pain, such as patients diagnosed with fibromyalgia syndrome.
\nWhen it comes to the treatment of musculoskeletal pain, Manual Therapy thus seems to be able to significantly modulate the nociceptive afferences of peripheral tissues, regardless of their structural specificity. Based on this, the literature seems to support a patient-centered clinical practice focused on the mechanisms of pain and musculoskeletal impairment that characterize it based on the reactivity of the clinical picture.
\nWhile no manual approach is superior to the others, the literature itself supports the use of techniques tailored to each individual patient, modulating the force applied during the technique (from low to high), the duration (from short to long), and the prepositioning of the tissues (from relaxed to pretensioned) and acting either within or away from the resistance [75].
\nIn patients (defined by Maitland as “pain dominant”) with a clinical picture characterized by severe, often nocturnal pain significantly limiting ROM, applying intense techniques will be difficult and unreasonable. It may therefore be very useful to use painless techniques, far from the tissue barrier and symptom elicitation, which have been shown to alleviate pain, but not to improve the patient’s ROM [99]. Witness patients suffering from phase II frozen shoulder or symptomatic disc herniation [100, 101]. On the contrary, or progressively upon decrease in pain, patients with joint limitations and mild/moderate pain elicitable at the end of the joint range (whom Maitland defines as “stiffness dominant”) will benefit from more intense, longer-lasting techniques carried out at the end of the joint range, possibly with the reproduction of a symptomatology during application, which have proven capable of improving both pain and ROM in these patients [102, 103]: phase III frozen shoulder or osteoarthritis clinical pictures can be considered as emblematic examples [100, 104].
\nWhile biomechanical elements such as an increased mechanical extensibility of the joint capsule cannot be completely ruled out, improvements in functional impairments such as ROM would seem to be linked to the ability of manual techniques to modulate peripheral nociceptive afferences, thereby acting on all related clinical phenomena [105].
\nThis would seem to be confirmed by the possibility of obtaining a short-term improvement in muscle strength following techniques specifically targeted towards soft tissues in patients with musculoskeletal pain [106, 107]. These observations have led several authors to support the usefulness of manual techniques also in the field of well-being and physical training, with the aim of achieving greater physical functionality. However, studies carried out on healthy subjects or in the absence of peripheral impairments have contradicted this hypothesis by not showing the same benefits in mobility, strength, and functionality found in patients suffering from musculoskeletal disorders [108, 109]. The link between pain and muscle strength, and the possibility that these may be modulated by manual techniques, can nonetheless be of particular clinical interest. Indeed, studies included in the literature have shown the possibility of identifying soft tissue impairments, even within non-specific frameworks, through active and resistance tests, especially when the said active and resistance tests are painful and recreate the symptoms typical of the patient [110]. For example, a dry needling treatment targeted towards multifidus muscle has been observed to be more effective if the patients reported pain while recruiting that muscle [110].
\nThese observations hint at the clinical value of a Manual Therapy clinical practice that is evidence-based as well as focused on the patient and the impairment that can characterize both them and their daily life.
\nJoint and soft tissue techniques can therefore focus on and be guided by:
Pain
High reactivity/low reactivity
ROM limitation
Osteokinematics
Soft tissue dysfunctions
Active/resistance tests
The aspects described so far mainly refer to techniques directed at the anatomical regions responsible for the clinical picture of the patient. However, in accordance with a Manual Therapy model based on the improvement of the patient’s function, Manual Therapy techniques can be useful in improving all the musculoskeletal impairments that can biomechanically and neurophysiologically contribute to the patient’s symptoms and daily limitations [35]. For instance, sedentary patients with lower back pain may benefit from the treatment of any limitations present at hip level, which due to phenomena related to referred pain and afferent convergence may support pain perception [111, 112, 113].
\nThese aspects can play an even more significant role in subjects with high functional requirements such as professional athletes, where the correct functionality of all the structures participating in a specific movement will be clinically central in enabling their being able to perform at high levels. A typical example is the clinical relevance of a limitation in ankle dorsiflexion in a volleyball player with patellofemoral pain syndrome [114].
\nThe advantages and limitations of Manual Therapy should be known in order to apply it in the best possible way. We know that the clinical effects that can be obtained in the treatment of musculoskeletal disorders tend to diminish over time after the end of the treatment, thereby often overlapping with the natural history of the disorder in the long term. This aspect is often highlighted by the opponents of manual techniques, who attribute many of the benefits observed in clinical practice to the benign and self-limiting nature of musculoskeletal disorders [115].
\nWhile these observations can be statistically accurate, it is important not to underestimate the role that an immediate modification of the symptom can play in the patient’s need for help [116]. Going back to professional athletes and their need for help, a rapid decrease in symptoms can enable one to resume sports activities just in time to take part in a cup final. The ability to use manual techniques in order to obtain benefits in the short term compared to mere therapeutic exercise will thus have a major impact on their daily activities and quality of life [117]. Similarly, we know that clinical pictures of symptomatic disc hernias have in most cases a positive prognosis within 3–6 months [118]. However, this data does not take into account the impact that a disorder of this type can have in the daily life of the patient in that period of time and the potential benefits of therapeutic techniques that have been shown to be able to significantly modify pain symptoms already in the first month [101]. Finally, symptom modification can play a very important educational role by enabling patients to realize that they are not the bearers of an incurable and unchangeable disorder, thereby acting on psychosocial factors that play an important prognostic role in the chronicity of the symptom [116].
\nAs written above, the presence of biomechanical and functional impairment can be very important in guiding the choice of the therapeutic technique to be used. However, non-biomechanical elements such as psychosocial factors can also mediate the clinical results that can be obtained through Manual Therapy techniques.
\nIn a standardized population of subjects with chronic neck pain, mobilization and joint manipulation techniques have shown to alleviate pain and improve ROM without statistically significant differences among the proposed techniques [76]. However, some elements present at the baseline, such as anxiety levels, were found to be associated with a different response to each technique [74]. As a matter of fact, patients with low anxiety levels showed more significant improvements following vertebral manipulation techniques, while more anxious subjects reported a greater reduction in pain when subjected to joint mobilization techniques. The psychosocial sphere can thus also be very important in the choice of the therapeutic method capable of producing the best clinical results, even in the short term.
\nIt is important to remember that evidence-based practice is based on three pillars: the preferences, needs and expectations of the patient, the expertise of the practitioner, and the available authoritative literature [11]. All these elements must be taken into account in the decision-making process. Their role is particularly significant in making clinical decisions with a risk of serious adverse events, such as choosing whether or not to perform risky heart surgery. However, they are also relevant in musculoskeletal rehabilitation and Manual Therapy.
\nPatient preferences have been shown to modulate the response to a specific treatment. For example, in the aforementioned study, the clinical response that could be obtained following vertebral manipulation techniques was also mediated by the opinion that the patients had of the proposed techniques [74]. Placebo mechanisms involving a descending inhibition of pain linked to expectation also seem to play a role in modulating the effectiveness of the techniques used based on the patient’s preferences [119]. Useful information can thus be obtained from the patient’s medical history. People who report having had negative results following soft tissue therapies and having responded very positively to manipulative techniques are likely to respond better to the latter. Clearly, the possible failure of a given therapeutic approach can be linked to purely clinical aspects, such as an incorrect classification of the patient. Subjects with pelvic pain may not respond to lumbar treatment techniques if the practitioner does not identify possible hip arthrosis as the real cause of the problem [113]. However, the information provided by the patient will play an important role by leading the practitioner to consider different evaluation and treatment hypotheses.
\nA second pillar of evidence-based practice involves the practitioner’s expertise and clinical competence. Also in this case, the possibility of modulating clinical effectiveness may be due to exclusively clinical or non-biomechanical aspects. The literature has shown that, in applying the same technique, the physiotherapist’s beliefs about the effectiveness of that specific technique were able to lead to different clinical responses in the patient [120]. This may be due once again to the expectations that, either explicitly or implicitly, the practitioner can give the patient when proposing and applying the said technique. In addition, the very mastery and confidence shown in the execution and application of the technique can convey the feeling of being in “good hands,” reduce the sense of threat, and activate central pain-inhibiting mechanisms [70].
\nFinally, even though the overlap in the clinical effectiveness of different Manual Therapy techniques has been pointed out several times, this entails basic competence in the application of these techniques. When the practitioner is not trained to perform a given technique, or does not have adequate clinical experience, they may have trouble in identifying the correct landmarks, in particular on small joints, or determining the adequate posology, thereby producing either no results at all or even harmful consequences.
\nAs a matter of fact, clinical practice in Manual Therapy is to be based on advanced knowledge enabling, first and foremost, the identification of patients who do not fall within the scope of rehabilitation and are to be referred to a physician or who may present contraindications to manual practice [121].
\nThere is a wide debate in the literature on the dangers of manual techniques, particularly with regard to possible vascular or nerve damage as a result of cervical manipulation. These events seem to be mainly related to inadequate background checks as to the patient’s medical history and ultimately to the failure to spot red flag factors [122]. In particular, ongoing cervical vascular disorders may initially arise only with symptoms related to the cervical level, thereby mimicking the presence of musculoskeletal disorders. An early identification of these clinical pictures can enable the practitioner to immediately refer the patient to a more suitable clinical management, avoiding the use of treatment techniques whose role will then have to be investigated in the medical–legal field [123]. However, it is worth remembering that there is no completely safe medical and rehabilitation procedure. Indeed, studies have described adverse events even following therapeutic massage sessions [124].
\nThe ability to recognize the appropriateness of any technique with regard to the individual patient will lead to the choice of the most appropriate type of intervention and its modulation, particularly in populations of patients with a higher risk of adverse events, such as pediatric or geriatric patients [125], without having to apply the dictates supported by a specific Manual Therapy training method.
\nManual Therapy is an extremely effective therapeutic method in the management of patients with pain and musculoskeletal disorders. Like any other therapeutic method, it has its pros but also its cons and drawbacks. Its effectiveness, as described above, is based on the ability to modify the functionality, albeit not the anatomy, of the patient’s tissues by means of mainly neurophysiological mechanisms [69].
\nTherefore, an appropriate and effective clinical practice can only be based on the correct classification of the patient, identifying first of all those clinical pictures, including musculoskeletal ones, which, according to the scientific literature, are not suitable for Manual Therapy, thereby orienting the patient towards a medical, pharmacological [126], or surgical approach [127], or a conservative program based on therapeutic exercise [128], or simply a “wait and see” strategy. Indeed, only by acknowledging the limits of Manual Therapy is it possible to strongly affirm its great merits and potential for alleviating the patient’s pain and improving their functionality in the short, medium, and long term [19, 20]. This will involve the great majority of patients with musculoskeletal pain, whose clinical picture is characterized by functional impairment, in particular reduction of ROM and peripheral hyperalgesia, with particular regard to soft tissues. In this respect, Manual Therapy is able to have a very positive effect, leading to rapid and significant improvements when properly applied in accordance with the specific clinical picture and the individual patient.
\nWhile there is no such thing as a superior Manual Therapy method, being free from the dogmas of a specific therapeutic approach allows for a truly patient-oriented clinical practice focused on the patient and their needs, choosing the most appropriate technique and modulating it from time to time on the basis of the clinical picture of that individual patient. This ability to provide a clinical framework and subsequently manage the manual approach proposed to the patient is what defines the role and real competence of healthcare professionals specializing in manual and manipulative therapy, with an approach strongly based on the biopsychosocial model.
\nWhile the current main limitation of Manual Therapy is the production of predominantly short-term responses, these observations are primarily based on studies that have investigated the effectiveness of individual techniques. However, we know that the therapeutic relationship in clinical practice is also made up of other things, such as the therapeutic alliance between practitioner and patient, understood as a person [70].
\nFor this reason, a healthcare professional trained in Manual Therapy according to an evidence-based approach can produce results even in the long term by exploiting the immediate reduction of the symptom and the rapid improvement of the functionality as a bridge to reduce the fear of movement and the related anxiety in the patient and stimulate an active coping towards their disorder [116], thereby making them gain confidence in their ability to perform “thoughtless, fearless movement” [129] through an especially active rehabilitation process.
\nOnly in this way can the professional improve their practice for the good of the patient, acting according to science and conscience and reaffirming the central role of their professional figure in the management of musculoskeletal disorders.
\nThe history of postmortem examination, commonly known as an autopsy, dates back to ancient Egyptian days, where there was considerable interest in the relationship of wounds and fractures to anatomy, but little interest in the nontraumatic diseases. It was not until the 20th century when leaders of medicine in North America, including Sir William Osler (1849–1919), emphasized the importance of the autopsy in medical education. The objectives of an autopsy would include the establishment of final diagnoses and of the causes of death, and the unique opportunity for physicians to correlate their clinical observations with pathologic changes of disease. The autopsy establishes a standard for evaluating the accuracy of pre-mortem diagnoses and outcome of therapy. It provides critical data for quality assurance and makes room for quality improvement. It also provides the surviving family the basis for genetic counseling for hereditary diseases, thereby directing preventative care for living family members, which is particularly true in cases of sudden death. Family members can be comforted by obtaining information on the causes of death of their loved ones, obtaining answers to questions surrounding terminal events, and irrational guilt can be alleviated [1, 2, 3, 4, 5].
The first step to any examination is to determine the identity of the individual. This can be carried out by law enforcement (who are usually the first responders to the death scene), or by the presiding Coroner or Medical Examiner. Thus, by the time the body arrives in the morgue, the identity has been determined.
Establishment of identity can occur through various methods. The degree of certainty is best classified as definitive, presumptive, or speculative. Definitive identification is legally sufficient, and it is based on the objective comparison of antemortem and postmortem information. This includes visual recognition (most widely used method of identification), fingerprints, dental record comparison, radiographs/unique anthropomorphic features and/or surgical devices (somewhere serial numbers can be obtained), and deoxyribonucleic acid (DNA) analysis. Presumptive identification is when positive identification has more likely than not been established. This includes recognition of clothing, unique tattoos, scars, birthmarks, or items at scene such as various papers, medication bottles, or identification bearing the decedent’s name. Speculative identification is an initial guess, which carries the lowest degree of certainty. In many instances, not one but many methods based on the circumstances surrounding the death, investigation of the scene, and examination of the body are used to accumulate sufficient evidence that points to the decedent’s identity [6]. Various special techniques such as artist’s sketches and reconstruction methods (forensic sculptors, computer programs) can also be employed in selected circumstances [7, 8].
External examination begins by obtaining measurements of height and weight without clothing, and any other features that may help with documentation (such as arm span, foot length, center of gravity from umbilicus to heel, etc.). Medical interventions should be documented, such as endotracheal tubes, intravascular catheters, penetrating tubes or wires. The descriptions should preferentially involve assessments of proper positioning of interventions through markings that are visible externally, as well as externally visible injuries associated with the interventions.
The overall appearance and assessment of nutritional status are also documented. Postmortem changes are assessed, which include the degree of rigor mortis, the distribution of livor mortis, and any other postmortem changes that may be present (decompositional changes of various degrees).
The rest of the external examination can be carried out in various orders depending on personal practice, but a logical way would be to start from the top of the head. The quality and distribution of hair over the head are recorded, together with observations of the scalp including skin conditions and/or injuries. The facial features are then documented, including descriptions of the eyes, ears, nose, mouth, and palpation of the bones of the face to identify any fractures underneath. Description of the eyes should include the color of the irides, and examination of the sclera and palpebral conjunctivae for any discoloration (e.g., scleral jaundice) and/or petechial hemorrhages. Evaluation of pupillary sizes after death is not indicative of their ante-mortem appearance due to early changes after death [9].
Examination of the neck should include documentation of any abnormal markings and injuries that may suggest self-harm and/or criminal actions. If injuries are suspected, a layered neck dissection procedure should be performed in a bloodless field (see Section 4 below).
Examination of the extremities aims to look for any deformities that may suggest acute or previous injuries, and scars or markings that may add to the social history (such as scars on the wrist in cases of self-harm, or track marks in cases of intravenous drug use). In certain criminal investigations, fingernails can be clipped and submitted for further testing that may link the victim to the assailant.
Examination of the torso follows, with documentation of overall size and shape that may suggest underlying diseases (such as a barrel chest in chronic obstructive pulmonary disease) and/or injuries (such as a flail chest in multiple rib fractures). Examination of the torso also includes the back, which is ideally performed with the body positioned prone on the table. Again, documentation of any abnormalities that may suggest disease or injuries is done, and the anus is also examined for any abnormalities.
The body is then positioned supine, lying on a block between the shoulder blades, and the internal examination can begin.
There are several ways of incising into the skin to expose the underlying structures. The most commonly employed skin incisions include the Y-shaped incision, the modified Y-shaped incision, and the I-shaped incision. The Y-shaped incision goes from the tips of the shoulder on each side obliquely down, joining at the middle of the chest, roughly between the nipples, and the incision is then continued down vertically along the midline of the front of the body, stopping at the pubis. The modified Y-shaped incision is when the top most incisions start from behind each ear down the sides of the neck toward the middle of the chest. The I-shaped incision is a single straight vertical incision that goes from the top of the neck down the midline of the front of the body to the pubis [10, 11].
The skin is then peeled back from the underlying bones, by cutting roughly parallel to the skin surface along the subcutaneous layer of soft tissues. The chest plate is removed by first separating the sternoclavicular joints, and cutting the ribs near the anterior costochondral junctions, preferably cutting through the cartilaginous parts so that the cut edges are relatively dull to reduce risk of injury during subsequent evisceration.
There are several techniques for evisceration (the removal of organs from body cavities) [12, 13]. The technique of Virchow employs removal of body organs one after another. This technique is good for demonstrating pathology in individual organs, but the relationships between various organs may be hard to interpret. The technique of Letulle or the en masse technique is when the cervical, thoracic, abdominal, and pelvic organs are removed as one mass, and then subsequently dissected into organ blocks. This technique is good for preserving vascular supply and relationships between organs. However, the organ mass is sometimes awkward to handle, and an assistant may be required to help with handling. The technique of Ghon or the en bloc technique is where the cervical and thoracic organs, the abdominal organs, and the urogenital system are removed as separate organ blocks. This is a mixture of the Virchow and en masse techniques, allowing the preservation of anatomical relationship sufficiently while enabling one person to execute without an assistant. Finally, the technique of Rokitansky consists of in-situ dissection combined with en bloc removal.
The organs are then examined individually, and any diseases and/or injuries are documented. During examination, sections of organs may be submitted for subsequent microscopic examination (see Section 5.1 below).
Selected procedures and techniques that differ from or are added to the routine autopsy are performed in certain situations to better demonstrate the diseases or injuries involved.
Pneumothorax is usually associated with injury to the lung, although pure pneumothorax, although rare, can happen. The pleural cavities, therefore, should be checked for the presence of air in cases of chest injuries.
The skin and muscle on the injured side of the chest are reflected and dissected to form a pocket lateral to the chest wall, just below the level of the axilla. This pocket is then filled with water, and a scalpel is introduced under the water level, incising into an intercostal space through to the pleural cavity. Air bubbles observed exiting through this incision represent presence of pneumothorax. An inverted graduated cylinder filled with water can be held over the pocket prior to the incision into the pleural cavity to collect and measure the amount of air in the pleural cavity if desired [14].
Deep vein thrombosis in the calves is frequently seen associated with cases of death by pulmonary embolism, and is a frequent complication of immobilization and/or trauma. With the body positioned prone, the calf is incised vertically from the heel to the popliteal fossa, and the skin is then reflected. The tendon of Achilles is severed, and the attached calf musculature is then reflected and dissected gently from the underlying tibia and fibula from the heel upward. Transverse sections through the reflected musculature are then performed, and thrombi, if present, will thus be transversely sectioned, and their relationship with the attached vessels can be visualized. Antemortem thrombi typically maintain their sausage-like shape even if they become dislodged from the vessels, and show a concentrically layered cut surface (an indication of antemortem organization) [14]. Postmortem clots are typically soft and collapsible in nature, and do not show concentric laminations on cut surfaces.
Examination of the neck structures can aid in determining injuries in the neck that may have medicolegal implications. The neck should be examined at the end of the autopsy following removal of all other organs including the brain so as to create a dry/bloodless field to minimize the possibility of introducing blood seepage into the neck structures during dissection.
The routine Y-incision is extended from the tips of both shoulders upward along the posterior-lateral aspects of the neck and behind the ears toward the level of mid-ear. The skin is then undermined and reflected from the shoulder regions to the ears, proceeding to the level of the mandible on both sides. Layerwise reflection of the muscles of the neck is then carried out and injuries of the anterior neck are documented. Examination of the posterior neck takes on a similar approach, which is most easily done with the body positioned prone. A single vertical incision from the protruding C7 spinous process up toward the midline occiput is coupled with a horizontal incision at the mid posterior neck, effectively creating a cross-shaped incision, where the skin can then be reflected back to expose underlying musculature. The posterior neck muscles are then reflected in a layerwise manner and examined for injuries.
Sometimes it is necessary to examine the soft tissues of the face, and the anterior skin flap can be further reflected by undermining the facial skin from the level of the mandible. Subcutaneous severing of the external auditory meatus will mobilize the skin for better visualization of the facial skull, and will not interfere with the cosmetic appearance of the face as long as midline attachments of skin to subcutaneous tissues are maintained at the midline of the face.
The middle and inner ears are encased in the petrous portions of the temporal bones, located at the base of the skull.
Following the removal of the brain, the dura is stripped from the middle fossa, and the petrous regions are dried. Bone cutters are used to excise the petrous ridge from all four sides to produce a roughly rectangular segment. The inner surface of the tympanic membrane is exposed and can be examined for evidence of inflammation. Findings of purulent inflammation should be reported and swabs may be submitted for culture. The entire petrous block can be decalcified and submitted for microscopic examination if so desired [14].
Air embolism should be suspected in cases involving an open wound to the neck area, diving misadventures, chest trauma, or cases associated with childbirth or abortions. An interrupted blood column at autopsy in cerebral or cardiac vessels is often artefactual and thus is not regarded as evidence of air embolism.
The pericardial sac is opened anteriorly, and the edges are grasped with tools such as forceps or hemostats to create a pocket. Water is poured into the sac and the heart is submerged. A scalpel is then used to incise into the right side of the heart under the water level. Bubbles will arise if air is present. For measurement, an inverted graduated cylinder filled with water can be placed in the water prior to incising the heart [14].
The presence of water in the sphenoid sinus, although recognized to be present in any body that has been immersed in water, is one extra finding that can lend support to cases of drowning, which remains a diagnosis of exclusion. A large-bore needle attached to a syringe is used to perforate the sphenoid bone on either side of the sella, while it is directed downward and medially at a 45° angle. An average of 2–3 ml (sometimes up to 5 ml) of water may be aspirated [14].
The spinal cord can be visualized or removed for further examination by either an anterior or posterior approach, traditionally by sawing through the pedicles (anterior approach) or the laminae (posterior approach) to expose the underlying spinal cord following the routine autopsy and removal of the brain. Alternatively, an intervertebral disc in the lumbar spine can be transected, as well as another intervertebral disc in the thoracic area. A Stryker saw is used to cut out the segment of vertebral bodies between the two transected discs. The exposed dura is visualized, and can be slit vertically and reflected sideways. The exposed portion of the cord/cauda is then loosened by severing the nerves within the spinal canal, and slow downward traction toward the feet can be applied to retrieve the remaining cord in its entirety [14, 15].
Examination of the cervical spine may be warranted in cases of traffic deaths, falls, diving deaths, and suspected shaken baby cases. One radiological study showed that cervical injuries in road crash victims can be above C3 (50% of cases) or below C3 (22% of cases) [16]. Injuries range from severe fractures and dislocations to a few deep hemorrhages in the musculature. Injuries to the vertebral artery can sometimes occur when hyperextension/flexion and rotational forces are in play, with the most vulnerable regions being the third section [17].
The body is placed face down, and a head block is placed under the chest, with the head flexed at the neck. A posterior midline incision is made, and the musculature dissected in a layered fashion down to the vertebral column. The atlanto-occipital joint capsules are incised into, so that the articular surfaces can be examined. The atlas is disarticulated and removed. Laminectomy is then performed on the cervical vertebrae, and the dura mater can be incised and the spinal cord examined prior to removal. The exposed underside of the base of the skull can now be examined for fractures [14].
To begin the vertebral artery examination, the brain should be examined for basal subarachnoid hemorrhage, and if present, the basilar artery can be clamped with a hemostat. The skull cap can be replaced to ensure stability. The vertebral arteries can then be accessed from its branching point from the subclavian artery (most often the first branch) and cannulated with an 8F catheter, and secured and sutured to ensure no leakage around the catheter. An anterior–posterior x-ray is then obtained, and each cannulated artery is injected with 3–5 ml of contrast medium repeatedly until the vessel is visible on x-ray. The lesion, if present, can be established radiographically, and the entire neck block can be excised by cutting around the foramen magnum superiorly and disarticulating the seventh cervical vertebra inferiorly [14]. Fixation and decalcification can then proceed, and the vertebral arteries and surrounding tissues can then be exposed and examined.
The brain is a soft structure that goes into decomposition quickly following death, thus making processing and examination difficulty in the fresh state. In addition, many brain findings can be subtle and require the tissue to sbe in optimal condition in order for these findings to be exhibited. Thus, it is advisable for the brain, following removal from the cranial cavity, to be suspended in a bucket of formalin using a string placed under the basilar artery of the circle of Willis, for at least a week and most optimally beyond 2 weeks prior to cutting into the brain parenchyma. The hardened tissue also provides better exhibits for photographing subtle lesions.
Some conditions (such as myocarditis) are diagnosed only on microscopic examination, with no specific corresponding gross findings. Forensic microscopy should be a part of investigations of sudden unexpected deaths, determination of the premortem nature of diseases or injuries, and interpretation and substantiation of gross findings (such as in cases of infections and/or malignancies). In my experience, samples of major organs (heart, lungs, liver, kidneys, and brain) should be microscopically examined in every autopsy.
Collection of postmortem specimens for toxicological testing has become almost routine for many institutions involved in death investigation, and can be performed with or without a complete internal examination. The routinely collected specimens include blood from a peripheral source, urine, vitreous humor, and liver tissue [18]. Other specimens that may be of value include bile and stomach contents.
Blood should be collected from a peripheral site such as the femoral vessels to minimize effects of postmortem redistribution of certain drugs. Collection can be achieved by inserting a large bore needle attached to a syringe through the skin, overlying the location of the femoral vessels (medial anterior inguinal regions), or internally by directly visualizing the vessels during the autopsy. Urine can be collected through the skin as well by inserting needle into the suprapubic area. Vitreous humor is collected by inserting needle into the whites (scleral portion) of the eyes, aiming toward the center of the globes.
Fluid specimens should be deposited and stored in glass tubes with sodium fluoride, to preserve the storage stability of drugs such as cocaine [19]. Vitreous fluid is also useful in the evaluation of diabetic complications, in that glucose and ketones are seen to increase substantially in cases of diabetic ketoacidosis [20].
The author declares no conflict of interest.
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\\n\\nThe aforementioned licenses shall survive the expiry or termination of this Agreement for any reason.
\\n\\n2.2 The Corresponding Author (on their own behalf and on behalf of any Co-Author) reserves the following rights to the Chapter but agrees not to exercise them in such a way as to adversely affect IntechOpen's ability to utilize the full benefit of this Publication Agreement: (i) reprographic rights worldwide, other than those which subsist in the typographical arrangement of the Chapter as published by IntechOpen; and (ii) public lending rights arising under the Public Lending Right Act 1979, as amended from time to time, and any similar rights arising in any part of the world.
\\n\\nThe Corresponding Author confirms that they (and any Co-Author) are and will remain a member of any applicable licensing and collecting society and any successor to that body responsible for administering royalties for the reprographic reproduction of copyright works.
\\n\\nSubject to the license granted above, copyright in the Chapter and all versions of it created during IntechOpen's editing process (including the published version) is retained by the Corresponding Author and any Co-Author.
\\n\\nSubject to the license granted above, the Corresponding Author and any Co-Author retains patent, trademark and other intellectual property rights to the Chapter.
\\n\\n2.3 All rights granted to IntechOpen in this Article are assignable, sublicensable or otherwise transferrable to third parties without the Corresponding Author's or any Co-Author’s specific approval.
\\n\\n2.4 The Corresponding Author (on their own behalf and on behalf of each Co-Author) will not assert any rights under the Copyright, Designs and Patents Act 1988 to object to derogatory treatment of the Chapter as a consequence of IntechOpen's changes to the Chapter arising from translation of it, corrections and edits for house style, removal of problematic material and other reasonable edits.
\\n\\n3. CORRESPONDING AUTHOR'S DUTIES
\\n\\n3.1 When distributing or re-publishing the Chapter, the Corresponding Author agrees to credit the Book in which the Chapter has been published as the source of first publication, as well as IntechOpen. The Corresponding Author warrants that each Co-Author will also credit the Book in which the Chapter has been published as the source of first publication, as well as IntechOpen, when they are distributing or re-publishing the Chapter.
\\n\\n3.2 When submitting the Chapter, the Corresponding Author agrees to:
\\n\\nThe Corresponding Author will be held responsible for the payment of the Open Access Publishing Fees.
\\n\\nAll payments shall be due 30 days from the date of the issued invoice. The Corresponding Author or the payer on the Corresponding Author's and Co-Authors' behalf will bear all banking and similar charges incurred.
\\n\\n3.3 The Corresponding Author shall obtain in writing all consents necessary for the reproduction of any material in which a third-party right exists, including quotations, photographs and illustrations, in all editions of the Chapter worldwide for the full term of the above licenses, and shall provide to IntechOpen upon request the original copies of such consents for inspection (at IntechOpen's option) or photocopies of such consents.
\\n\\nThe Corresponding Author shall obtain written informed consent for publication from people who might recognize themselves or be identified by others (e.g. from case reports or photographs).
\\n\\n3.4 The Corresponding Author and any Co-Author shall respect confidentiality rights during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Corresponding Author and any Co-Author are confidential and are intended only for the recipient. The contents may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
\\n\\n4. CORRESPONDING AUTHOR'S WARRANTY
\\n\\n4.1 The Corresponding Author represents and warrants that the Chapter does not and will not breach any applicable law or the rights of any third party and, specifically, that the Chapter contains no matter that is defamatory or that infringes any literary or proprietary rights, intellectual property rights, or any rights of privacy. The Corresponding Author warrants and represents that: (i) the Chapter is the original work of themselves and any Co-Author and is not copied wholly or substantially from any other work or material or any other source; (ii) the Chapter has not been formally published in any other peer-reviewed journal or in a book or edited collection, and is not under consideration for any such publication; (iii) they themselves and any Co-Author are qualifying persons under section 154 of the Copyright, Designs and Patents Act 1988; (iv) they themselves and any Co-Author have not assigned and will not during the term of this Publication Agreement purport to assign any of the rights granted to IntechOpen under this Publication Agreement; and (v) the rights granted by this Publication Agreement are free from any security interest, option, mortgage, charge or lien.
\\n\\nThe Corresponding Author also warrants and represents that: (i) they have the full power to enter into this Publication Agreement on their own behalf and on behalf of each Co-Author; and (ii) they have the necessary rights and/or title in and to the Chapter to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licenses expressed to be granted in this Publication Agreement. If the Chapter was prepared jointly by the Corresponding Author and any Co-Author, the Corresponding Author warrants and represents that: (i) each Co-Author agrees to the submission, license and publication of the Chapter on the terms of this Publication Agreement; and (ii) they have the authority to enter into this Publication Agreement on behalf of and bind each Co-Author. The Corresponding Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each such Co-Author.
\\n\\nThe Corresponding Author agrees to indemnify and hold IntechOpen harmless against all liabilities, costs, expenses, damages and losses and all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of or in connection with any breach of the aforementioned representations and warranties. This indemnity shall not cover IntechOpen to the extent that a claim under it results from IntechOpen's negligence or willful misconduct.
\\n\\n4.2 Nothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\\n\\n5. TERMINATION
\\n\\n5.1 IntechOpen has a right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Corresponding Author or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Corresponding Author or any Co-Author (being an individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Corresponding Author or any Co-Author (being a company) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for or enters into any compromise or arrangement with any of its creditors.
\\n\\nIn case of termination, IntechOpen will notify the Corresponding Author, in writing, of the decision.
\\n\\n6. INTECHOPEN’S DUTIES AND RIGHTS
\\n\\n6.1 Unless prevented from doing so by events outside its reasonable control, IntechOpen, in its discretion, agrees to publish the Chapter attributing it to the Corresponding Author and any Co-Author.
\\n\\n6.2 IntechOpen has the right to use the Corresponding Author’s and any Co-Author’s names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Chapter and has the right to contact the Corresponding Author and any Co-Author until the Chapter is publicly available on any platform owned and/or operated by IntechOpen.
\\n\\n6.3 IntechOpen is granted the authority to enforce the rights from this Publication Agreement, on behalf of the Corresponding Author and any Co-Author, against third parties (for example in cases of plagiarism or copyright infringements). In respect of any such infringement or suspected infringement of the copyright in the Chapter, IntechOpen shall have absolute discretion in addressing any such infringement which is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\\n\\n7. MISCELLANEOUS
\\n\\n7.1 Further Assurance: The Corresponding Author shall and will ensure that any relevant third party (including any Co-Author) shall, execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\\n\\n7.2 Third Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\\n\\n7.3 Entire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces and extinguishes all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (together "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of its pre-contract fraudulent misrepresentation or fraudulent concealment.
\\n\\n7.4 Waiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\\n\\n7.5 Variation: No variation of this Publication Agreement shall be effective unless it is in writing and signed by the parties (or their duly authorized representatives).
\\n\\n7.6 Severance: If any provision or part-provision of this Publication Agreement is or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted.
\\n\\nAny modification to or deletion of a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\\n\\n7.7 No partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Corresponding Author or any Co-Author, nor authorize any party to make or enter into any commitments for or on behalf of any other party.
\\n\\n7.8 Governing law: This Publication Agreement and any dispute or claim (including non-contractual disputes or claims) arising out of or in connection with it or its subject matter or formation shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of or in connection with this Publication Agreement (including any non-contractual disputes or claims).
\\n\\nLast updated: 2020-11-27
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The Corresponding Author (acting on behalf of all Authors) and INTECHOPEN LIMITED, incorporated and registered in England and Wales with company number 11086078 and a registered office at 5 Princes Gate Court, London, United Kingdom, SW7 2QJ conclude the following Agreement regarding the publication of a Book Chapter:
\n\n1. DEFINITIONS
\n\nCorresponding Author: The Author of the Chapter who serves as a Signatory to this Agreement. The Corresponding Author acts on behalf of any other Co-Author.
\n\nCo-Author: All other Authors of the Chapter besides the Corresponding Author.
\n\nIntechOpen: IntechOpen Ltd., the Publisher of the Book.
\n\nBook: The publication as a collection of chapters compiled by IntechOpen including the Chapter. Chapter: The original literary work created by Corresponding Author and any Co-Author that is the subject of this Agreement.
\n\n2. CORRESPONDING AUTHOR'S GRANT OF RIGHTS
\n\n2.1 Subject to the following Article, the Corresponding Author grants and shall ensure that each Co-Author grants, to IntechOpen, during the full term of copyright and any extensions or renewals of that term the following:
\n\nThe aforementioned licenses shall survive the expiry or termination of this Agreement for any reason.
\n\n2.2 The Corresponding Author (on their own behalf and on behalf of any Co-Author) reserves the following rights to the Chapter but agrees not to exercise them in such a way as to adversely affect IntechOpen's ability to utilize the full benefit of this Publication Agreement: (i) reprographic rights worldwide, other than those which subsist in the typographical arrangement of the Chapter as published by IntechOpen; and (ii) public lending rights arising under the Public Lending Right Act 1979, as amended from time to time, and any similar rights arising in any part of the world.
\n\nThe Corresponding Author confirms that they (and any Co-Author) are and will remain a member of any applicable licensing and collecting society and any successor to that body responsible for administering royalties for the reprographic reproduction of copyright works.
\n\nSubject to the license granted above, copyright in the Chapter and all versions of it created during IntechOpen's editing process (including the published version) is retained by the Corresponding Author and any Co-Author.
\n\nSubject to the license granted above, the Corresponding Author and any Co-Author retains patent, trademark and other intellectual property rights to the Chapter.
\n\n2.3 All rights granted to IntechOpen in this Article are assignable, sublicensable or otherwise transferrable to third parties without the Corresponding Author's or any Co-Author’s specific approval.
\n\n2.4 The Corresponding Author (on their own behalf and on behalf of each Co-Author) will not assert any rights under the Copyright, Designs and Patents Act 1988 to object to derogatory treatment of the Chapter as a consequence of IntechOpen's changes to the Chapter arising from translation of it, corrections and edits for house style, removal of problematic material and other reasonable edits.
\n\n3. CORRESPONDING AUTHOR'S DUTIES
\n\n3.1 When distributing or re-publishing the Chapter, the Corresponding Author agrees to credit the Book in which the Chapter has been published as the source of first publication, as well as IntechOpen. The Corresponding Author warrants that each Co-Author will also credit the Book in which the Chapter has been published as the source of first publication, as well as IntechOpen, when they are distributing or re-publishing the Chapter.
\n\n3.2 When submitting the Chapter, the Corresponding Author agrees to:
\n\nThe Corresponding Author will be held responsible for the payment of the Open Access Publishing Fees.
\n\nAll payments shall be due 30 days from the date of the issued invoice. The Corresponding Author or the payer on the Corresponding Author's and Co-Authors' behalf will bear all banking and similar charges incurred.
\n\n3.3 The Corresponding Author shall obtain in writing all consents necessary for the reproduction of any material in which a third-party right exists, including quotations, photographs and illustrations, in all editions of the Chapter worldwide for the full term of the above licenses, and shall provide to IntechOpen upon request the original copies of such consents for inspection (at IntechOpen's option) or photocopies of such consents.
\n\nThe Corresponding Author shall obtain written informed consent for publication from people who might recognize themselves or be identified by others (e.g. from case reports or photographs).
\n\n3.4 The Corresponding Author and any Co-Author shall respect confidentiality rights during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Corresponding Author and any Co-Author are confidential and are intended only for the recipient. The contents may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
\n\n4. CORRESPONDING AUTHOR'S WARRANTY
\n\n4.1 The Corresponding Author represents and warrants that the Chapter does not and will not breach any applicable law or the rights of any third party and, specifically, that the Chapter contains no matter that is defamatory or that infringes any literary or proprietary rights, intellectual property rights, or any rights of privacy. The Corresponding Author warrants and represents that: (i) the Chapter is the original work of themselves and any Co-Author and is not copied wholly or substantially from any other work or material or any other source; (ii) the Chapter has not been formally published in any other peer-reviewed journal or in a book or edited collection, and is not under consideration for any such publication; (iii) they themselves and any Co-Author are qualifying persons under section 154 of the Copyright, Designs and Patents Act 1988; (iv) they themselves and any Co-Author have not assigned and will not during the term of this Publication Agreement purport to assign any of the rights granted to IntechOpen under this Publication Agreement; and (v) the rights granted by this Publication Agreement are free from any security interest, option, mortgage, charge or lien.
\n\nThe Corresponding Author also warrants and represents that: (i) they have the full power to enter into this Publication Agreement on their own behalf and on behalf of each Co-Author; and (ii) they have the necessary rights and/or title in and to the Chapter to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licenses expressed to be granted in this Publication Agreement. If the Chapter was prepared jointly by the Corresponding Author and any Co-Author, the Corresponding Author warrants and represents that: (i) each Co-Author agrees to the submission, license and publication of the Chapter on the terms of this Publication Agreement; and (ii) they have the authority to enter into this Publication Agreement on behalf of and bind each Co-Author. The Corresponding Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each such Co-Author.
\n\nThe Corresponding Author agrees to indemnify and hold IntechOpen harmless against all liabilities, costs, expenses, damages and losses and all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of or in connection with any breach of the aforementioned representations and warranties. This indemnity shall not cover IntechOpen to the extent that a claim under it results from IntechOpen's negligence or willful misconduct.
\n\n4.2 Nothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\n\n5. TERMINATION
\n\n5.1 IntechOpen has a right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Corresponding Author or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Corresponding Author or any Co-Author (being an individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Corresponding Author or any Co-Author (being a company) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for or enters into any compromise or arrangement with any of its creditors.
\n\nIn case of termination, IntechOpen will notify the Corresponding Author, in writing, of the decision.
\n\n6. INTECHOPEN’S DUTIES AND RIGHTS
\n\n6.1 Unless prevented from doing so by events outside its reasonable control, IntechOpen, in its discretion, agrees to publish the Chapter attributing it to the Corresponding Author and any Co-Author.
\n\n6.2 IntechOpen has the right to use the Corresponding Author’s and any Co-Author’s names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Chapter and has the right to contact the Corresponding Author and any Co-Author until the Chapter is publicly available on any platform owned and/or operated by IntechOpen.
\n\n6.3 IntechOpen is granted the authority to enforce the rights from this Publication Agreement, on behalf of the Corresponding Author and any Co-Author, against third parties (for example in cases of plagiarism or copyright infringements). In respect of any such infringement or suspected infringement of the copyright in the Chapter, IntechOpen shall have absolute discretion in addressing any such infringement which is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\n\n7. MISCELLANEOUS
\n\n7.1 Further Assurance: The Corresponding Author shall and will ensure that any relevant third party (including any Co-Author) shall, execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\n\n7.2 Third Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\n\n7.3 Entire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces and extinguishes all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (together "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of its pre-contract fraudulent misrepresentation or fraudulent concealment.
\n\n7.4 Waiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\n\n7.5 Variation: No variation of this Publication Agreement shall be effective unless it is in writing and signed by the parties (or their duly authorized representatives).
\n\n7.6 Severance: If any provision or part-provision of this Publication Agreement is or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted.
\n\nAny modification to or deletion of a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\n\n7.7 No partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Corresponding Author or any Co-Author, nor authorize any party to make or enter into any commitments for or on behalf of any other party.
\n\n7.8 Governing law: This Publication Agreement and any dispute or claim (including non-contractual disputes or claims) arising out of or in connection with it or its subject matter or formation shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of or in connection with this Publication Agreement (including any non-contractual disputes or claims).
\n\nLast updated: 2020-11-27
\n\n\n\n
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I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. 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