bluuebunny/crossref_metadata_2025 huggingface dataset:
DNCON2: improved protein contact prediction using two-level deep convolutional neural networks
Authors: Adhikari Badri , Hou Jie , Cheng Jianlin
Published: December 2017

Motivation

Significant improvements in the prediction of protein residue–residue contacts are observed in the recent years. These contacts, predicted using a variety of coevolution-based and machine learning methods, are the key contributors to the recent progress in ab initio protein structure prediction, as demonstrated in the recent CASP experiments. Continuing the development of new methods to reliably predict contact maps is essential to further improve ab initio structure prediction.

Results

In this paper we discuss DNCON2, an improved protein contact map predictor based on two-level deep convolutional neural networks. It consists of six convolutional neural networks—the first five predict contacts at 6, 7.5, 8, 8.5 and 10 Å distance thresholds, and the last one uses these five predictions as additional features to predict final contact maps. On the free-modeling datasets in CASP10, 11 and 12 experiments, DNCON2 achieves mean precisions of 35, 50 and 53.4%, respectively, higher than 30.6% by MetaPSICOV on CASP10 dataset, 34% by MetaPSICOV on CASP11 dataset and 46.3% by Raptor-X on CASP12 dataset, when top L/5 long-range contacts are evaluated. We attribute the improved performance of DNCON2 to the inclusion of short- and medium-range contacts into training, two-level approach to prediction, use of the state-of-the-art optimization and activation functions, and a novel deep learning architecture that allows each filter in a convolutional layer to access all the input features of a protein of arbitrary length.

Availability and implementation

The web server of DNCON2 is at http://sysbio.rnet.missouri.edu/dncon2/ where training and testing datasets as well as the predictions for CASP10, 11 and 12 free-modeling datasets can also be downloaded. Its source code is available at https://github.com/multicom-toolbox/DNCON2/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Learning from the History of Integrative Preventive Medicine to Address Our Current Healthcare Challenges
Authors: Jonas Wayne B. , Calabrese Edward
Published: December 2017

Integrative medicine (IM), defined as the appropriate use of all evidence-based healthcare practices and professions—complementary and conventional—is evolving as an important aspect of preventive medicine in the last twenty years to achieve population health. With the creation of the National Prevention, Health Promotion and Public Health Council in the United States, representing cabinet-level agencies, there was an opportunity to truly reform the basic approach to preventive medicine from an integrative perspective. Other advances in prevention show the steady global progress of integrative preventive medicine (IPM) in both concept and operations. As these developments evolve, what lessons can we learn from the last twenty years of IM to make a difference in establishing and maintaining a healthy and resilient population in the twenty-first century? This chapter summarizes some of those lessons and describes a vision for IPM in addressing the current health challenges faced by the world.
Integrative Medicine and the Social Determinants of Health
Authors: Satcher David
Published: December 2017

This chapter explores the overlap and potential synergies of integrative medicine and preventive medicine in the context of levels of prevention, acknowledging the relative deficiency of research on the effectiveness of practice-based integrative care. The goal of integrative medicine should be to make the widest array of appropriate options available to patients, ultimately blurring the boundaries between conventional care and CAM. Both disciplines should be subject to rigorous scientific inquiry so that interventions that work are systematically distinguished from those that do not. The case is made that responsible use of science and responsiveness to the needs of patients that persist when the data from randomized controlled trials have been exhausted can be reconciled. Integrative medicine is a framework for this reconciliation and, practiced judiciously, offers the promise of better patient outcomes.
Health Literacy and Cultural Competence in Integrative Preventive Health and Medicine
Authors: Pleasant Andrew , Cabe Jennifer
Published: December 2017

As the United States and the world continue to experience unsustainable growth in the rates of chronic disease and rising healthcare costs, most urgently needed are upstream solutions—far before the point of people needing and seeking medical treatment. What is required to address this untenable situation is a shift in the underlying premises of the health and medical philosophies and infrastructure. This chapter will propose that an evidence-based solution lies in a convergence between an integrative approach to health and medicine and health literacy. That convergence inherently embraces cultural competency and leads health systems, healthcare professionals, and the people they serve to work together as a newly integrated whole that is greater than the sum of the parts.
Place and Well-Being
Authors: Lindberg Casey M. , Banasiak Meredith A. , Shindler Ryan M. , Sternberg Esther M.
Published: December 2017

Various fields of research have developed to better understand the health and behavioral effects of environmental characteristics such as air quality and the way our homes and neighborhoods are organized. A synergy of many previously disparate fields of research is underway, aided in part by recent advances in technology. Better sensors, including wearable physiological and environmental monitors, are enabling researchers to more readily study the interactions between environment characteristics and both mental and physical well-being. This new evidence-based research direction adds a much-needed layer of quantitative data to previous, largely qualitative, findings. Moreover, an increased understanding of the environment’s effects on humans can result in not just the alleviation of negative environmental characteristics but also the promotion of positive environmental characteristics. This chapter offers samples of environmental effects on human health and well-being in the following categories: environmental quality, natural systems, sensory environments, physical activity, safety, and social connectedness.
An Integrative Preventive Medicine Approach to Primary Cancer Prevention
Authors: Greenlee Heather , Sanders Kathleen , Moran Zelda
Published: December 2017

Cancer is a major cause of morbidity and mortality, with the number of new global cases estimated to reach 21.4 million in 2030. The increase in cancer incidence is due not only to aging populations and increased life expectancies but also to unhealthy lifestyle practices, environmental exposures, and a lack of effective and accessible prevention programs. Knowledge of evidenced-based cancer prevention strategies is crucial for healthcare providers and patients. This chapter describes both conventional medical and integrative medicine approaches to primary cancer prevention. Integrative medicine is an emerging field within cancer prevention and control. This chapter describes what is and is not known about the effectiveness of integrative medicine approaches to cancer prevention. An optimal preventive healthcare approach should include cancer prevention programs that integrate all evidence-based conventional and integrative medicine treatment approaches and options.
Aging, Brain Plasticity, and Integrative Preventive Medicine
Authors: Merzenich Michael M.
Published: December 2017

This chapter reviews aging and the brain from an important, alternative, still-underappreciated scientific and medical perspective. It briefly describes the history of brain plasticity-related neuroscience, then describes change processes that shape our brains in ways that ultimately distinguish the typical struggling older versus peak-performing younger brain. It considers how and why processes that contribute to personal growth at a younger age are commonly thrown into reverse at an older age. It reviews the development of new brain science–based tools that appear to throw the “plasticity switch” for brain health back in a corrective and strengthening direction, where change processes again support the growth and the more reliable maintenance of physical and functional brain health. Finally, it summarizes how this translational science shall almost certainly evolve to enable a new, neuroscience-directed medical era of brain health management for our older-age populations.
An Integrative Approach to the Assessment and Treatment of Inflammatory Conditions
Authors: Liponis Mark , Martin Bettina
Published: December 2017

The past two decades have seen great progress in recognizing the importance of inflammation in medicine. Increased focus on inflammation in both prevention and treatment has improved outcomes and quality of life in chronic diseases. Science has improved our understanding of inflammation’s many causes and effects on health, and many advances have been made in the availability of targeted therapeutic options for treating inflammation. This chapter gives an overview of recognizing the many causes of inflammation, its many targeted treatments strategies, and the questions that still surround it. It discusses several integrative approaches to reducing inflammation, including exercise, diet, and different strategies for managing sleep, mood, and stress, such as meditation and massage.
Sleep and Preventive Health—An Integrative Understanding and Approach
Authors: Dedhia Param
Published: December 2017

This chapter focuses on the role of sleep in optimal prevention and begins by introducing the epidemiology of sleep, the history of sleep, and how sleep has been defined in modern medicine. It emphasizes the importance of sleep stages and cycles and the need for both quality and adequate quantity of sleep, and covers common sleep disorders. It discusses the role sleep plays in waking performance and consequently public safety, and how disrupted or disordered sleep is correlated with disease and illness. Finally, this chapter introduces a variety of interventions and treatments for disrupted and disordered sleep—including the treatment of sleep-related breathing disorder, Willis-Ebkom disease, and insomnia—and integrative approaches and lifestyle habits that can help promote optimal sleep.
The Gerontological Imagination
Authors: Ferraro Kenneth F.
Published: December 2017

The Gerontological Imagination provides an integrative overview of the scientific study of aging. Although investigators from many disciplines study aging, concerns have been raised about the intellectual coherence of gerontology precisely because it draws from and contributes to a wide array of disciplines. Biologists, psychologists, and sociologists may claim an interest in gerontology, but do they have a common image of aging or a set of principles to guide their research? This book develops a paradigm for the study of aging by articulating and integrating six axioms related to causality, life course analysis, multifaceted change, heterogeneity, accumulation, and ageism. The proposed paradigm provides an efficient way to identify essential ideas, findings, models, and theories across multiple disciplines. Gerontology examines aging across multiple systems and the interplay of factors that shape adaptation. Illustrations are drawn from fields such as biology, epidemiology, genetics, medicine, psychology, sociology, and zoology. The axioms are best viewed as a gestalt for the intellectual work of research on aging—and how to optimize the aging experience.
Accumulation Processes
Authors: Ferraro Kenneth F.
Published: December 2017

Accumulation is a core concept in gerontology, but there is inconsistency in how scholars use the term to describe age-related processes. This chapter identifies the axiom of accumulation processes and reinforces axioms articulated in other chapters, especially multifaceted change. Accumulation involves a gradual amassing of some entity, but the utility of the concept for research on aging hinges on specifying the attributes of the entity and manner in which accumulation occurs. To advance conceptual precision in the use of the term, I delineate ways in which entities may accumulate, isolating concepts such as domains, timing, thresholds, and systemic change. A study of men’s use of supplements to prevent prostate cancer is described to illustrate the importance of accounting for nonlinear thresholds of accumulation.
Mechanical Ventilation
Authors: Kreit John W. , Kellum John A.
Published: December 2017

Mechanical Ventilation—Physiology and Practice provides a comprehensive review of the physiological principles underlying mechanical ventilation, as well as practical approaches to the management of patients with respiratory failure. The book explains instrumentation and terminology, ventilator modes and breath types, ventilator alarms, how to write ventilator orders, and how to diagnose and correct patient–ventilator asynchrony. It also discusses the physiological assessment of the mechanically ventilated patient and the diagnosis and management of dynamic hyperinflation, and describes how to manage patients with the acute respiratory distress syndrome (ARDS), severe obstructive lung disease, and right ventricular failure; how to “wean” patients from the ventilator; and how and when to use noninvasive ventilation.
Gas Exchange
Authors: Kreit John W.
Published: December 2017

Gas Exchange explains how four processes—delivery of oxygen, excretion of carbon dioxide, matching of ventilation and perfusion, and diffusion—allow the respiratory system to maintain normal partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) in the arterial blood. Partial pressure is important because O2 and CO2 molecules diffuse between alveolar gas and pulmonary capillary blood and between systemic capillary blood and the tissues along their partial pressure gradients, and diffusion continues until the partial pressures are equal. Ventilation is an essential part of gas exchange because it delivers O2, eliminates CO2, and determines ventilation–perfusion ratios. This chapter also explains how and why abnormalities in each of these processes may reduce PaO2, increase PaCO2, or both.
Ventilator Modes and Breath Types
Authors: Kreit John W.
Published: December 2017

Ventilator Modes and Breath Types describes, compares, and contrasts the different modes and breath types that are available on intensive care unit ventilators. The chapter first covers the various ventilator modes: continuous mandatory ventilation, synchronized intermittent mandatory ventilation, spontaneous ventilation, and bi-level ventilation. Then it turns to a discussion of the various mechanical breath types: volume control, pressure control, adaptive pressure control, pressure support, and finally, adaptive pressure support. It also provides practical advice about how and when to use each mode–breath type combination. Eight Boxes in the chapter discuss each breath type, and list each type’s features, and its clinician-set parameters.
How to Write Ventilator Orders
Authors: Kreit John W.
Published: December 2017

How to Write Ventilator Orders provides step-by-step instructions on how to write ventilator orders—how to choose appropriate settings immediately after intubation; how to adjust ventilator settings throughout the course of the patient’s illness; and when weaning the patient from mechanical ventilation—how to write orders for spontaneous breathing trials. For writing initial ventilator orders, we discuss: choosing a mode of mechanical ventilation, choosing the type of mechanical breath, selecting settings based on the type of mechanical breath, and specifying other basic settings. Next, the chapter covers recommended adjustments to settings in cases of high PaO2 and SpO2, low PaO2 andSpO2, and respiratory acidosis and alkalosis. A table at the end of the chapter shows the orders needed to perform an on-ventilator spontaneous breathing trial.
Physiological Assessment of the Mechanically Ventilated Patient
Authors: Kreit John W.
Published: December 2017

This chapter reviews the tests that can be used to determine the type and severity of respiratory failure and the extent to which one or more of the components of normal ventilation and gas exchange have been compromised by disease. Physiological Assessment of the Mechanically Ventilated Patient describes the bedside procedures, measurements, and calculations that allow the assessment of gas exchange and respiratory mechanics in mechanically ventilated patients. Topics include co-oximetry and pulse oximetry, arterial blood gas measurements, venous admixture and shunt fraction, the dead space to tidal volume ratio, time- and volume-capnography, measurement of peak and plateau pressures, and calculation of respiratory system compliance and resistance.
Dynamic Hyperinflation and Intrinsic Positive End-Expiratory Pressure
Authors: Kreit John W.
Published: December 2017

Dynamic hyperinflation and intrinsic PEEP almost always occur in patients with severe obstructive lung disease, in whom slowing of expiratory flow prevents complete exhalation. Occasionally, patients without airflow obstruction develop dynamic hyperinflation when expiratory time, is excessively shortened by a rapid respiratory rate, a long set inspiratory time (TI), or both. Dynamic Hyperinflation and Intrinsic Positive End-Expiratory Pressure describes the causes of dynamic hyperinflation and the mechanisms of its adverse effects, including reduced cardiac output and blood pressure, pulmonary barotrauma, and ineffective ventilator triggering. The chapter also describes how to screen for and measure intrinsic PEEP, and how to reduce or eliminate its adverse effects.
Severe Obstructive Lung Disease
Authors: Kreit John W.
Published: December 2017

Although chronic obstructive lung disease, asthma, bronchiectasis, and bronchiolitis have very different causes, clinical features, and therapies, they share the same underlying pathophysiology. They are referred to as obstructive lung diseases because airway narrowing causes increased resistance and slowing of expiratory gas flow. Mechanical ventilation of patients with severe obstructive lung disease often produces two problems that must be recognized and effectively managed: over-ventilation and dynamic hyperinflation. Severe Obstructive Lung Disease reviews these two major adverse consequences of mechanical ventilation in patients with severe air flow obstruction. The chapter explains how to detect and correct both of these problems and provides guidelines for managing patients with respiratory failure caused by severe obstructive lung disease.
Genetic Methodologies and Applications
Authors: Purcell Shaun M.
Published: December 2017

Mental illness is highly heritable, yet it has been difficult historically to identify the specific genes that comprise that risk. This difficulty resides in the fact that the genetic risk for all common mental disorders is polygenic, with perhaps hundreds of genetic variations, each of small effect, contributing to the overall risk. Despite these challenges, the field has made dramatic advances over the past decade in beginning to understand the genetic basis of mental illness. This chapter provides an overview of the experimental approaches used, beginning with epidemiology and population genetics to define the heritability of an illness, to classic studies of large families and linkage disequilibrium analysis, to genome-wide investigations including genome-wide association studies (GWAS), exome sequencing, and whole genome sequencing. Increasingly, these genetic advances are being understood within the biological context of disease pathophysiology.
Network Methods for Elucidating the Complexity of Common Human Diseases
Authors: Schadt Eric E.
Published: December 2017

The life sciences are now a significant contributor to the ever expanding digital universe of data, and stand poised to lead in both the generation of big data and the realization of dramatic benefit from it. We can now score variations in DNA across whole genomes; RNA levels and alternative isoforms, metabolite levels, protein levels, and protein state information across the transcriptome, metabolome and proteome; methylation status across the methylome; and construct extensive protein–protein and protein–DNA interaction maps, all in a comprehensive fashion and at the scale of populations of individuals. This chapter describes a number of analytical approaches aimed at inferring causal relationships among variables in very large-scale datasets by leveraging DNA variation as a systematic perturbation source. The causal inference procedures are also demonstrated to enhance the ability to reconstruct truly predictive, probabilistic causal gene networks that reflect the biological processes underlying complex phenotypes like disease.
Methods for In Vivo Gene Manipulation
Authors: Monteggia Lisa M. , Xu Wei
Published: December 2017

Recent advances in mouse genetics have opened many new avenues of research in which to explore gene function in the brain, and contributions to the pathophysiology and treatment of psychiatric disorders. The use of the mouse to explore gene function has contributed a better understanding of the role of specific genes in the nervous system including their influence on neural circuits and complex behavior.

This chapter explores current approaches to manipulate gene function in a mouse. Genetically modified mice allow for the investigation of a particular gene in vivo. The approaches discussed highlight recent advances to specifically overexpress or disrupt a specific gene of interest in the brain. We also highlight viral-mediated gene transfer approaches to allow for spatial and temporal control of gene function.
Application of Stem Cells to Understanding Psychiatric Disorders
Authors: Brennand Kristen
Published: December 2017

While much has been learned through clinical post-mortem and neuroimaging studies of patients and animal models of autism spectrum disorder (ASD), bipolar disorder (BD) and schizophrenia (SZ), these classical approaches have yet to fully elucidate the interaction of complex genetic risk factors on disease predisposition. The derivation of human induced pluripotent stem cells (hiPSCs) from patients with psychiatric disorders permits the study of the full complement of risk variants (known and unknown) that underlie disease predisposition, precisely in the cell types relevant to disease. The following chapter covers work to date regarding the advancements in the use of hiPSCs to model psychiatric disorders.
Immune Mechanisms of Depression
Authors: Ménard Caroline , Pfau Madeline L. , Hodes Georgia E. , Russo Scott J.
Published: December 2017

Mood disorders such as major depressive disorder (MDD) are diagnosed largely based upon behavioral symptoms rather than biological factors. Some have argued that a lack of rigorous biomarker-based diagnosis is the reason why 30%–50% of MDD patients are unresponsive to traditional antidepressant medications. Over the past few decades, MDD has been shown to be highly prevalent in patients suffering from chronic inflammatory conditions, such as lupus erythematosus, multiple sclerosis, etc. Moreover, subgroups of MDD patients have shown consistently higher levels of circulating pro-inflammatory cytokines. Together, these clinical findings suggest that alterations within the immune system might contribute to the behavioral symptoms of MDD. In this chapter, we review the growing literature in both humans with MDD and in rodent stress models of depression that support a role for the immune system in depression.
Synaptic and Circuit Mechanisms of Anxiety Disorders
Authors: Li Anfei , Lee Francis S.
Published: December 2017

A fundamental issue in treating anxiety disorders—and many other mental illnesses—is the lack of mechanistic understanding of the underlying pathophysiology. Recent studies, both in human and rodent, have taken the steps to elucidate the key brain regions and circuits that are implicated in anxiety disorders. In this chapter, we highlight how human and rodent studies can complement each other, and how an integrative approach provides bridges between the relevant but complex and imprecise phenomenology of human behavior and the solid findings of rodent neurobiology that can be difficult to extrapolate to human behavior and anxiety disorders. Recent findings in both humans and rodent models, and more importantly, how the two models have complemented each other, have enhanced our understanding of the pathophysiology of anxiety disorders.
The Neurobiology of Resilience
Authors: Feder Adriana , Horn Sarah R. , Haglund Margaret , Southwick Steven M. , Charney Dennis S.
Published: December 2017

Resilience is the ability to adapt successfully in the face of severe stress, trauma, or adversity. Over the past several decades, a wide range of studies in children and later in adults identified several key psychosocial characteristics associated with resilience, including emotion regulation, cognitive flexibility, positive emotions, and the availability of social support, among others. More recent studies are increasingly employing integrative approaches, incorporating genomic, neuroendocrine, and neuroimaging data to the study of resilience. This chapter reviews our current understanding of the neurobiology of resilience from genomic, developmental, psychosocial, neuroendocrine, brain circuitry, and integrative perspectives, and includes a final section focusing on implications for prevention and treatment of stress-related psychopathology.
Animal Models of Addiction
Authors: Christopher Evans J. , Kieffer Brigitte L. , Jentsch David , Maldonado Rafael J.
Published: December 2017

Drug addiction, now officially diagnosed as substance use disorder (SUD), is a chronic brain syndrome characterized by the compulsive use of drugs, loss of control over drug taking in spite of its adverse consequences, and relapse even after long periods of drug abstinence. Animal models have played a critical role in our understanding of the molecules, circuits, and behaviors associated with substance use disorders. This chapter reviews animal models that have been widely used to assess all stages of the addiction cycle: from drug initiation, through drug seeking, to withdrawal and relapse. We discuss the power of genetics, especially in generating rodent models for the discovery of essential proteins and pathways regulating behaviors exhibited during the different stages of the addiction cycle. Preclinical research in animal models will undoubtedly continue to reveal therapeutic strategies for substance use disorders.
Diagnosis and Epidemiology of Dementia
Authors: Kreisl William C. , Reitz Christiane
Published: December 2017

Dementia is a neurodegenerative clinical syndrome encompassing a wide range of diseases characterized by progressive deterioration in cognitive ability, function and behavior. More than 24 million people worldwide are currently affected, and this prevalence is predicted to quadruple by the year 2050. The most common cause of dementia is Alzheimer’s disease, clinically characterized by a progressive impairment in cognitive function. To date, Alzheimer’s disease cannot be prevented or cured; the available treatments only slightly improve cognitive symptoms. In this chapter, we provide an overview of the most common neurodegenerative causes of dementia, beginning with Alzheimer’s disease, and summarize current information relating to the prevalence and incidence of dementia.
Neurobiology of FTD
Authors: Chung Dah-Eun Chloe , Stankowski Jeannette N. , Petrucelli Leonard
Published: December 2017

Frontotemporal dementia (FTD) is the third most common form of dementia, and is one that predominantly affects the frontal and temporal lobes. Pathological heterogeneity of FTD is highlighted in various types of protein inclusions in the brain, which can include tau, TDP-43, or FUS. The discovery of novel genes and mutations associated with FTD, along with the exciting advancement of molecular technologies, led to the development of numerous animal- and human-based model systems. These valuable models allow not only for the investigation of pathogenic mechanisms underlying FTD, but also for their utilization as powerful platforms for the screening of novel therapies.
Population ageing in South and Central America
Authors: Junior Carlos M. Paixao , Lourenço Roberto A. , Morales-Martínez Fernando
Published: December 2017

Considering questions related to South and Central America probably is best done by using the better-known term of Latin America. Although much of the history of the region has common roots, many specificities make these countries somewhat heterogeneous. However, one can say that ageing in the region has been accelerated and diverse from what was witnessed in more affluent countries elsewhere in the world, because of the persistent problem of poverty still unresolved in Latin America. The over-60 population has been growing in the region for the past 30 years, producing an increase in old-age indices and old-age dependency ratios. This raises important issues about the social protection models that should be adopted to cope with these demographic trends.
Population ageing in Oceania
Authors: Flicker Leon , Kerse Ngaire
Published: December 2017

The region of Oceania describes a collection of islands scattered throughout the Pacific Ocean between Asia and the Americas. The region is vast and largely covered by ocean. There are four subregions of this region including Australasia (Australia and New Zealand), Melanesia (Papua and New Guinea, Fiji, Solomon Islands, Vanuatu, and New Caledonia), Micronesia (Federated States of Micronesia and Guam), and Polynesia (includes French Polynesia, Samoa, Tonga, Tokalau, and Niue). Australasia is relatively affluent and developed with an ageing population, whereas the other nations are of a developing nature with relatively younger populations but will face dramatic population ageing over the next 40 years. Australasia has well-developed services for older people. The Indigenous populations of Australasia have worse health outcomes than the non-Indigenous populations. However, outside Australasia there is an urgent need to develop health and community services for older people in the remainder of the region.
Implications of population ageing for societies and governments
Authors: Beard John R. , Pot Anne Margriet , Peeters Geeske
Published: December 2017

Population ageing presents both opportunities and challenges to societies and governments. While even today, the economic contribution of older people is likely to outweigh the expenditure on them by governments, this balance could be even more positive in the future. Yet, outdated stereotypes of ageing are pervasive and limit the way older people are viewed and the way policy is framed. Moving forward will require a broader understanding of the diversity of older populations, the inequities that underpin it, and of the many and varied opportunities for societal responses that can enable the abilities of older people. What population ageing ultimately implies for societies and governments will therefore depend as much on societal attitudes and response as it will on the intrinsic capacities and needs of older populations.
Policy options for responding to population ageing
Authors: Sidorenko Alexandre , Walker Alan
Published: December 2017

We live in the time of multifaceted societal transition: demographic, familial, and epidemiological. All three transitions are advancing globally, though not universally, and there are enduring deviations. All three transitions bring us significant and welcome opportunities: longer, healthier, and potentially more fulfilling lives. Healthier and happier citizens should benefit their societies and promote development. However, the above opportunities are accompanied by challenges. After highlighting the major challenges and opportunities of ageing societies, the chapter turns to reviewing the international policy frameworks on ageing, focusing on the Madrid International Plan of Action on Ageing and its regional implementation strategies. A brief overview of international policy players in the area of ageing is also included.
Ageing, multimorbidity, and daily functioning
Authors: Gryglewska Barbara , Piotrowicz Karolina , Grodzicki Tomasz
Published: December 2017

Multimorbidity is defined as any combination of a chronic disease with at least one other acute or chronic disease or biopsychosocial or somatic risk factor. Old age is a leading risk factor for multimorbidity. It has a negative impact on short- and long-term prognosis, patients’ cognitive and functional performance, self-care, independence, and quality of life. It substantially influences patients’ clinical management and increases healthcare-related costs. There is a great variety of clinical measures to assess multimorbidity; some are presented in this chapter. Despite its high prevalence in older adults, clinical guidelines for physicians managing patients with multimorbidity are underdeveloped and insufficient.
Engaging older patients in their treatment and care
Authors: Coulter Angela
Published: December 2017

Nowadays we use the term ‘patient-centred care’ to describe responsiveness to people’s personal, practical, emotional, and social needs alongside their biomedical ones. This chapter looks at what patient-centred care means for older people, what they want from healthcare, and how to ensure that the healthcare they receive is appropriate to their needs. Despite evidence that most patients, including those in the oldest age groups, want to be informed and involved in decisions about their care, there is a gap between these aspirations and the reality. This chapter looks at evidence on what patients want and expect. Ways in which clinicians can support them to become active partners in their care are discussed and evidence on what works is briefly reviewed. Examples include shared decision-making, personalized care planning, use of advance care plans, technologies to support independent living, and care coordination.
Interprofessional team building and case management
Authors: Flaherty Ellen , Fulmer Terry
Published: December 2017

Interprofessional team care (ITC) and case management are essential to achieve the best patient-centred outcomes for complicated older adults with multiple comorbidities. Case management in geriatrics refers to a process of care coordination. Caring for complex geriatric patients with multiple chronic conditions requires the development and implementation of individualized, coordinated plans of care. Such plans of care often call for further evaluation, treatment, referrals, and patient or caregiver education, or both. Typically, this care coordination occurs in an interprofessional team of geriatric healthcare providers—which may include physicians, geriatric nurses, pharmacists, psychiatrists, therapists, and social workers. The components of good team care include effective communication, conflict resolution, understanding and respecting team member’s and responsibilities, and team governance. Formal training is necessary to achieve these skills. Providing efficient and effective team care is both challenging and critical in an environment of accountable care with a burgeoning over-85 population.
Limitations in the evidence for safe and effective medications for older people
Authors: Cherubini Antonio , Onder Graziano
Published: December 2017

In the last decades, evidence-based medicine has emerged as the approach to promote the best clinical practice for health problems. It collates the best published evidence, preferentially based on randomized clinical trials, to guide clinical practice. However, the growing older population challenges the evidence underpinning ‘best practice’. Many older patients are characterized by multimorbidity and polypharmacotherapy, present various degrees of functional and cognitive impairment, and are at risk of developing geriatric syndromes. For these reasons they have been almost systematically excluded from clinical trials. In addition, the results of clinical trials are difficult to apply to patients with these characteristics, given the high risk of drug–drug and drug–disease interactions. An effort to promote a greater involvement of older patients in clinical research is needed, using specific measures to facilitate the participation of complex older patients, who are representative of those treated in clinical practice.
Legal and ethical issues in care of older adults
Authors: Tilvis Reijo
Published: December 2017

Widely accepted ethical principles are taken into account in several international declarations and recommendations, but national legislations of care for old people are characterized by wide diversity. Ethical considerations go further than pure clinical assessments and include all consequences of starting and/or withholding of cure and care. The oldest Hippocratic principles—beneficence (doing good) and non-maleficence (not harming)—are obligations of physicians to act in the best interest of the patients. Autonomy, the existence and feeling of freedom of choice and self-governance, has replaced paternalism, and is cherished in Western culture. Sufficient information and capacity of the patient are preconditions for giving informed consent before any treatment is undertaken. In cases of lacking capacity, the healthcare providers must consult family members or other proxy persons to find out what the patient’s wish might have been. Advanced statements of wishes or advanced directives can help to avoid surrogate decisions.
Integrating geriatrics principles into primary care
Authors: Cruz-Jentoft Alfonso J.
Published: December 2017

Care of older people living in the community relies on primary care physicians. When the accumulation of ageing, chronic conditions, or acute problems has an impact on physical or mental function, comprehensive geriatric care has to be incorporated in usual primary care to understand, coordinate, manage, and prevent diseases and disabilities.

Primary care physicians play key roles in the care of older subjects, including prevention and screening for diseases and geriatric problems, management of chronic disease and multimorbidity, detection and management of frailty and early disability, home, end-of-life and nursing home care, and continuity and customization of care. Incorporation of geriatric principles may improve performance and outcomes in each of these tasks.

In addition, using some elements of comprehensive geriatric assessment in primary care management of older patients may help to improve outcomes.
Older people presenting to acute care hospitals
Authors: Wong Roger Y. M.
Published: December 2017

Older people presenting to acute care hospitals are at risk of developing adverse events. Comprehensive geriatric assessment (CGA) in acute care provides standardized assessment and management of geriatric problems. The emergency department is a common point of entry, and strategies that focus on enhancing expertise, equipment, policies, and protocols are helpful. The geriatric consultation service model is commonly deployed, and the geriatric evaluation and management unit (GEMU) is a common ward-based model. The acute care for elders (ACE) unit model is associated with fewer adverse events, less functional decline, shorter hospital length of stay, lower institutionalization risk, and lower cost. The senior friendly hospital (SFH) model requires further studies to confirm its effectiveness. A number of geriatric post-discharge liaison services can smooth the transition of older people returning to the community. Overall these models of care are not mutually exclusive, but together they comprise the best practice for older people.
Post-acute care and intermediate care
Authors: Chen Liang-Kung
Published: December 2017

Post-acute care (PAC), interchangeable with intermediate care, is the key to the success of healthcare services for older people. Due to the need for longer periods of recovery from acute insults, PAC provides the opportunities for these patients to regain functional independence, as well as reduction in hospital readmission and premature long-term care placement. Moreover, the functional recovery obtained from PAC services is associated with the reduction in one-year mortality by 62%. Different models of PAC services have been developed internationally, including home care models, community hospitals, day hospitals, nurse-led units, and community rehabilitation teams. The success of PAC depends on person-centred care with a multidisciplinary approach and comprehensive geriatric assessment, which is consistent in different PAC models. Some specific clinical conditions occurring in PAC possess unique characteristics and impact on PAC outcomes. These conditions are not exclusive to PAC, but their presence may strongly influence quality of care.
Transitions between care settings until death
Authors: Gundersen Elizabeth C. , Bensadon Benjamin A. , Ouslander Joseph G.
Published: December 2017

The problem of poor care transitions in geriatric patients is complex and challenging, and one which has become a priority across healthcare systems. Various interventions have shown success in improving transitions in care, but there is no one solution and more progress must yet be made, especially in the care of our most vulnerable patients, including those with dementia or at the end of life. Perhaps the most commonly recurring themes, however, are the need for multifaceted interventions and increased patient- and family-centred care. It is essential to discuss goals of care with patients and families, and then form treatment plans—including discharge plans—which respect those goals. Geriatric and palliative care clinicians are uniquely suited to contribute their skills in this area to improve care transitions.
Why do organisms age?
Authors: Kirkwood Thomas B. L.
Published: December 2017

The study of the underpinnings of ageing provides insight not only into the kinds of genetic factors that influence the ageing process, but also into the physiological mechanisms influencing ageing and longevity. Notions that ageing was necessary to create living space for future generations, or to facilitate turnover of the population, are generally unsound. Instead, ageing is thought to have its evolutionary origins in how the force of natural selection declines with age, the later portions of the lifespan being under indirect evolutionary control. The most widely supported explanation of why organisms age is the disposable soma theory. This posits that, under pressure of selection to make the best use of available resources, genomes evolved to put only enough effort into cellular maintenance to keep the individual in sound condition through the period that it might normally have been expected to survive and reproduce in ancestral, wild environments.
Age-related physiologic declines
Authors: Fabbri Elisa , Zoli Marco , Ferrucci Luigi
Published: December 2017

‘How and why living organisms age?’ This question has puzzled and challenged philosophers and scientists for centuries. Ageing can be defined as a progressive loss of anatomic and physiological integrity across multiple systems and organs, leading to impaired function and higher vulnerability to adverse health outcomes and death. Although the biological mechanisms that trigger and accelerate ageing are still not understood, enormous steps forward in delineating the effects of ageing has been made in recent years. Ageing induces morphological and physiological changes across multiple organs and systems, which result in progressive loss of resilience, increased vulnerability to stressors, disease susceptibility, and development of physical and cognitive frailty, disability, and adverse outcomes.
Biological significance of gut microbiota changes associated with ageing
Authors: Horgan Kevin , Shanahan Fergus , O’Toole Paul W.
Published: December 2017

The concept that the commensal gut microbiota might influence the ageing process is not new. Awareness of the gastrointestinal microbiota and its potential role in host health was recognized in the late nineteenth century. Metchnikoff was a proponent of the value of fermented foods in promoting healthy ageing and proposed that the beneficial effect was a consequence of modulation of the resident colonic bacterial ‘flora’. His conviction could not be substantiated because of the lack of tools necessary to address the issue rigorously in that era. A century later, advanced technology has established the role of the human microbiota in health and disease. Emerging information is leading to a fundamentally revised understanding of many aspects of human development and disease that takes into account the role of the microbiota. This chapter addresses current knowledge of the relationship of the microbiome to human ageing, and outlines the prospects for monitoring and modulating the gut microbiota to promote healthy ageing.
Conceptualizing geriatric syndromes
Authors: Rikkert Marcel G. M. Olde
Published: December 2017

Geriatric syndromes, such as falling, delirium, and malnutrition, are common in older patients, and characterized by the presence of several disorders at the same time. These geriatric syndromes can be divided into acute (e.g. delirium) and non-acute (e.g. dizziness, falls) geriatric syndromes. The main criterion of multicausality is directly linked to frailty in older patients, as frailty results in a closer linkage and increased interaction between organ functions, which explains why several organs, diseases, and stressors are involved in each geriatric syndrome. There is interesting preliminary evidence for the existence of generic warning signals for the recurrence of acute geriatric syndromes, of which the most important is slowing down of recovery after a perturbation of the organ functions involved in a geriatric syndrome. All these pathophysiological mechanisms have important implications for diagnostic work up and treatment of geriatric syndromes, which together makes up the main part of geriatric patient care.
Urinary incontinence
Authors: Wagg Adrian
Published: December 2017

Lower urinary tract symptoms and urinary incontinence are highly prevalent in older persons. The physiological changes which occur in the ageing lower urinary tract, combined with neurological alterations in control of continence and micturition conspire to impair control of continence in older persons. In addition to the impact of coexisting medical comorbidities and lower urinary tract disease, this makes urinary incontinence and the ability to successfully toilet a typical geriatric syndrome, requiring multicomponent intervention to achieve the best possible outcome. There are emerging data on the efficacy of treatments in older and frail older persons which, if appropriately applied with regard to the individual, should result in amelioration of symptoms and bother, or socially contained continence for the most medically complex older person.
Pressure injuries in the ageing population
Authors: Kiely Cindy , Pupiales Magdalena
Published: December 2017

The prevalence of pressure ulcers has been reported to range from 4.1 to 32.2% in the older adult population. Pressure ulcers, also known as decubitus ulcers, bedsores, and pressure sores, are defined as localized injury to the skin and/or underlying structures, usually over a bony prominence as result of pressure or pressure in combination with shear. Within the geriatric population, prevalence and incidence rates tend to be high due to multifactorial risk factors such as comorbidities, changes in functional status, nutritional habits, medications affecting the skin, and physiological changes. The impact of pressure ulcers spans physical, emotional, social, and economic dimensions, and is of concern throughout the healthcare continuum. The aim of this chapter is to illustrate the aetiologic complexity of pressure ulcers in the geriatric population and summarize a comprehensive approach to prevention and management of pressure ulcers.