Books on the topic 'Biological heterogeneity'

Alzheimer’s disease and vascular dementia are acknowledged as the two most common types of dementia. Each of these dementia syndromes are associated with prodromal clinical syndromes, often referred to as mild cognitive impairment. Recent research has demonstrated considerable heterogeneity regarding the underlying neuropathology associated with these dementia syndromes and their prodromal disorders. Thus, it is often difficult to understand how or what underlying biological substrate is actually responsible for the alterations in neurocognition and behaviour as seen in clinical evaluations. This inherent neuropsychological and neuropathology heterogeneity calls into question current paradigms used for diagnosis and clinical trials designed to treat these disorders. This volume summarizes our current understanding regarding the inherent clinical, neuropathological, and biological heterogeneity in Alzheimer’s disease, vascular dementia, and mild cognitive impairment and suggests that these disorders are best viewed as existing along a continuum rather than treated as separate and distinct clinical syndromes. In this book, we put forth the point of view that dementia such as Alzheimer’s disease and vascular dementia; and subtle pre-dementia syndromes such as mild cognitive impairment are best viewed as existing along a continuum rather than distinct and separate disorders.

The dystonias are a large group of disorders characterized by excessive muscle activity leading to abnormal movements. They are clinically diverse, affecting different parts of the body at all ages in both humans and other animals. They also are etiologically diverse, with causes that are either inherited due to specific dystonia-causing genes, or acquired because of nervous system injury or exposure to certain drugs or chemicals. Despite the clinical and etiological heterogeneity, there is an increasing appreciation that certain subgroups of dystonias share some biological abnormalities at the molecular, cellular, anatomical, or physiological levels.

Negative views of aging are pervasive and pernicious, and arise, in part, from a failure to recognize the heterogeneity of the older adult population. Many people, at various ages, view the aging process pejoratively, thereby exaggerating the declines associated with growing older, Ageism also may entail unfair treatment toward older people, often manifest as neglect and exclusion. The consequences of ageism are notable, including accelerated declines in biological, psychological, and social functioning as well as ignoring or minimizing the intellectual and creative potential of older adults. To counter negative views of growing older, examples of late life genius and creative endeavor are profiled.

The management of idiopathic inflammatory myopathies (IIM) poses a challenge due to disease heterogeneity, variable responses to treatment and limited data from controlled studies. High dose glucocorticoids, often combined with other immunosuppressive drugs, represent the most common pharmacotherapeutic approach. The importance of early commencement of supervised exercise is also stressed. In treatment resistant cases, the introduction of drug combinations is recommended, and intravenous immunoglobulins may also be effective. Currently available data do not support use of most biological agents in the treatment of IIM, except possibly rituximab, which appears potentially effective in patients with myositis specific autoantibodies. The presence of organ involvement should prompt more aggressive treatment. A multidisciplinary approach should be adopted in most IIM patients.

This chapter discusses the aetiology of depression. It begins with an overview of reasons why the aetiology of depression has been and still is difficult to define, including its heterogeneity and the wider philosophical and methodological challenges involved. It then considers life events and social determinants of depression as well as psychological factors relevant to depression, including childhood development and early experiences, parenting style, and personality and personality disorders. It also examines cognitive behavioural theories of depression, neuropsychology, and psychodynamic theories, along with the role of unconscious processes and ego psychology in the aetiology of depression. Finally, the chapter describes the biological determinants of depression, paying attention to genetics, neurochemical changes in the brain, and stress and thyroid hormones.

A primary goal of the research domain criteria (RDoC) project from the National Institute of Mental Health in the United States is to better characterize and understand the pathology and etiology of mental illness by examining constructs with biological underpinnings and their effects on psychiatric symptoms. This endeavor shows promise in helping to better conceptualize dysfunction in the field of eating disorders, where there appears to be great heterogeneity within diagnostic groups. Treatments designed for a particular diagnosis may result in improved remission rates if they instead target underlying mechanisms of eating disorder symptoms. This system is not without challenge and limitations, however. This chapter includes a brief review of relevant literature on the proposed RDoC functional domains in eating disorders and discussion of the benefits and costs of this type of approach in improving patient care.

The lifetime prevalence of 15% for major depressive disorder (MDD) within the general population is among the highest among all mental disorders. MDD is also one of the leading causes of disability and has been estimated to affect 300 million people worldwide. Clinical, functional, and biological correlates of MDD are frequently investigated almost exclusively based on research that defines depression as a categorical disorder assessed by established diagnostic instruments. Given the phenotypic and biological heterogeneity of depression, a refocus of the clinical phenotype of depression is required and widely recommended. Cognitive dimensions of depression have long been implicated in the nature of depression as a disorder that is characterized by typically impaired cognitive and emotional processes. The systems of cognitive function, emotion processing, and social cognitive processing are regarded as comprehensively describing large parts of the clinical symptoms as well as the pathophysiology of the brain-based disorder of depression. The focus on the above cognitive and emotional dimensions of depression offers promising extended and novel diagnostic and treatment approaches ranging from pharmacological to psychological interventions targeting those dimensions of depression. This book aims to provide an improved understanding of the characteristics of the dimensional approach of depression, focusing on the cognitive, emotional, and social cognitive processes.

Essentials of Landscape Ecology is a new, comprehensive text that presents the principles, theory, methods, and applications of landscape ecology in an engaging and accessible format, supplemented by numerous examples and case studies from a variety of systems, including freshwater and marine “scapes.” Human activity has transformed landscapes worldwide on a scale that rivals or exceeds even the largest of natural forces, giving rise to a new geological age, the Anthropocene. As humans alter the structure and function of landscapes, the biological diversity and ecological relationships within those landscapes are also inevitably altered, to the extent that this may interfere with humanity’s efforts to sustain the productivity and multifunctional use of these landscapes. Landscape ecology has thus emerged as a new, multidisciplinary science to investigate the effects of human land use and environmental heterogeneity on ecological processes across a wide range of scales and systems: from the effects of habitat or resource distributions on the individual movements, gene flow, and population dynamics of plants and animals; to the human alteration of landscapes affecting the structure of biological communities and the functioning of entire ecosystems; to the sustainable management of natural resources and the ecosystem goods and services upon which society depends.

Reduction and reductionism have been central philosophical topics in analytic philosophy of science for more than six decades. Together they encompass a diversity of issues from metaphysics and epistemology. This article provides an introduction to the topic that illuminates how contemporary epistemological discussions took their shape historically and limns the contours of concrete cases of reduction in specific natural sciences. The unity of science and the impulse to accomplish compositional reduction in accord with a layer-cake vision of the sciences, the seminal contributions of Ernest Nagel on theory reduction and how they strongly conditioned subsequent philosophical discussions, and the detailed issues pertaining to different accounts of reduction that arise in both physical and biological science (e.g., limit-case and part-whole reduction in physics, the difference-making principle in genetics, and mechanisms in molecular biology) are explored. The conclusion argues that the epistemological heterogeneity and patchwork organization of the natural sciences encourages a pluralist stance about reduction.

Chronic pain disorders are prevalent and a large burden on health care resources. Around 10% of the general population report chronic widespread pain, which is the defining feature of fibromyalgia. Fibromyalgia is a poorly understood idiopathic disorder which is also characterized by widespread tenderness and commonly occurs with comorbid mood disorders, fatigue, sleep disturbance, and cognitive dysfunction. A role for genetics in chronic pain disorders has been identified by twin studies, with heritability estimates of around 50%. Susceptibility genes for chronic pain are likely to be involved in pain processing or the psychological component of these disorders. A number of genes have been implicated in influencing how pain is perceived due to mutations causing monogenic pain disorders or an insensitivity to pain from birth. The role of common variation, however, is less well known. The findings from human candidate gene studies of musculoskeletal pain to date are discussed. However, the scope of these studies has been relatively limited in comparison to other complex conditions. Identifying susceptibility loci will help to determine the biological mechanisms involved and potentially new therapeutic targets; however, this is a challenging research area due to the subjective nature of pain and heterogeneity in the phenotype. Using more quantitative phenotypes such as experimental pain measures may prove to be a more fruitful strategy to identify susceptibility loci. Findings from these studies and other potential approaches are discussed.

Chronic pain disorders are prevalent and a large burden on health care resources. Around 10% of the general population report chronic widespread pain, which is the defining feature of fibromyalgia. Fibromyalgia is a poorly understood idiopathic disorder which is also characterized by widespread tenderness and commonly occurs with comorbid mood disorders, fatigue, sleep disturbance, and cognitive dysfunction. A role for genetics in chronic pain disorders has been identified by twin studies, with heritability estimates of around 50%. Susceptibility genes for chronic pain are likely to be involved in pain processing or the psychological component of these disorders. A number of genes have been implicated in influencing how pain is perceived due to mutations causing monogenic pain disorders or an insensitivity to pain from birth. The role of common variation, however, is less well known. The findings from human candidate gene studies of musculoskeletal pain to date are discussed. However, the scope of these studies has been relatively limited in comparison to other complex conditions. Identifying susceptibility loci will help to determine the biological mechanisms involved and potentially new therapeutic targets; however, this is a challenging research area due to the subjective nature of pain and heterogeneity in the phenotype. Using more quantitative phenotypes such as experimental pain measures may prove to be a more fruitful strategy to identify susceptibility loci. Findings from these studies and other potential approaches are discussed.

This chapter reviews advances in pathogenesis; European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria with clinical, laboratory, and ultrasound criteria for classification as polymyalgia rheumatica (PMR); the heterogeneity and overlap between PMR, inflammatory arthritis, and large-vessel vasculitis as illustrated by representative cases; recent guidelines on early and correct recognition, investigations, and management of PMR; the scope of disease-modifying agents; socio-economic impact, outcomes, and patient experience in PMR. It also discusses areas for future research including clinical trials with biological agents and newer steroid formulations, standardized outcome assessments, and the search for better biomarkers in PMR. PMR is one of the common inflammatory rheumatic diseases of older people and represents a frequent indication for long-term glucocorticoid (GC) therapy. It is characterized by abrupt-onset pain and stiffness of the shoulder and pelvic girdle muscles. Its management is subject to wide variations of clinical practice and it is managed in primary or secondary care by general practitioners (GPs), rheumatologists, and non-rheumatologists. The evaluation of PMR can be challenging, as many clinical and laboratory features may also be present in other conditions, including other rheumatological diseases, infection, and neoplasia. PMR is usually diagnosed in the primary care setting, but standard clinical investigations and referral pathways for suspected PMR are unclear. The response to standardized therapy is heterogeneous, and a significant proportion of patients do not respond completely. There is also an overlap with inflammatory arthritis and large-vessel vasculitis for which adjuvant disease-modifying medications are often used. Prolonged corticosteroid therapy is associated with a variety of side effects, especially when high-dose glucocorticoid therapy is employed. Giant cell arteritis (GCA) is also often linked to PMR. It is a vasculitis of large- and medium-sized vessels causing critical ischaemia. GCA is a medical emergency because of the high incidence of neuro-ophthalmic complications. Both conditions are associated with a systemic inflammatory response and constitutional symptoms. The pathogenesis is unclear. The initiating step may be the recognition of an infectious agent by aberrantly activated dendritic cells. The key cell types involved are CD4+ T cells and macrophages giving rise to key cytokines such as interferon-γ‎ (implicated in granuloma formation), PDGF (intimal hyperplasia), and interleukin (IL)-6 (key to the systemic response). The pathogenesis of PMR may be similar to that of GCA, although PMR exhibits less clinical vascular involvement. The mainstay of therapy is corticosteroids, and disease-modifying therapy is currently indicated in relapsing disease.

Psoriasis is a chronic skin condition affecting about 3% of Europeans and North Americans. About 15% of people afflicted with psoriasis will develop psoriatic arthritis—cutaneous risk factors for this are psoriasis of the nails, scalp, and flexures. Since most cases of arthritis develop in people with psoriasis, new screening tools, both clinical and imaging, are available. Some genetic factors may also explain susceptibility and severity. Historically, five clinical subgroups have been described but these may be simplified to axial and peripheral involvement, the latter dividing into oligo- and polyarticular patterns. The importance of these clinical subdivisions is still under debate and research but it is clear that there is marked heterogeneity in all manifestations of this disease. In recent times the importance of extra-articular features has gained prominence such that the metabolic syndrome and cardiovascular morbidity are now seen as important features of 'psoriatic disease'. The diverse changes seen in bone on imaging reflect both the underlying pathogenic mechanisms and the ways in which the disease progresses. Recent work with animal models and immunohistochemistry has further advanced our understanding of these features. In the biologic era renewed interest in psoriatic arthritis has stimulated research into outcome assessment and permitted clearer understanding of how these new drugs work on the different aspects of the disease. In addition, improved recognition of the impact of the disease on the person has stimulated the development of new patient-reported outcome tools.

Psoriasis is a chronic skin condition affecting about 3% of Europeans and North Americans. About 15% of people afflicted with psoriasis will develop psoriatic arthritis—cutaneous risk factors for this are psoriasis of the nails, scalp, and flexures. Since most cases of arthritis develop in people with psoriasis, new screening tools, both clinical and imaging, are available. Some genetic factors may also explain susceptibility and severity. Historically, five clinical subgroups have been described but these may be simplified to axial and peripheral involvement, the latter dividing into oligo- and polyarticular patterns. The importance of these clinical subdivisions is still under debate and research but it is clear that there is marked heterogeneity in all manifestations of this disease. In recent times the importance of extra-articular features has gained prominence such that the metabolic syndrome and cardiovascular morbidity are now seen as important features of ’psoriatic disease’. The diverse changes seen in bone on imaging reflect both the underlying pathogenic mechanisms and the ways in which the disease progresses. Recent work with animal models and immunohistochemistry has further advanced our understanding of these features. In the biologic era renewed interest in psoriatic arthritis has stimulated research into outcome assessment and permitted clearer understanding of how these new drugs work on the different aspects of the disease. In addition, improved recognition of the impact of the disease on the person has stimulated the development of new patient-reported outcome tools.