bluuebunny/crossref_metadata_2025 huggingface dataset:
Case Study: BUILDing Ties with the Business Community
Authors: Oestman Katherine , Bello Rosalind , Chennisi Catherine , Brewster Anna
Published: May 2019

This chapter provides a case study which shows how building ties with the business community has sustained and expanded local efforts to improve community health and wellness. The case study centers on Pasadena, Texas. This example highlights how businesses can be a powerful partner in promoting economic development and creating community health as well as in sustaining and expanding health improvement initiatives through funding, strategic partnership, and implementation support.
Building Off of Evidence-Based Policies: The CDC’s Health Impact in 5 Years (HI-5) Initiative and CityHealth, an Initiative of the de Beaumont Foundation and Kaiser Permanente
Authors: Skillen Elizabeth , Hearne Shelley
Published: May 2019

This chapter discusses the importance of evidence and describe work in the CDC's HI-5 Initiative and the de Beaumont Foundation's CityHealth program to distill the broad range of evidence on effective policies into a form more readily actionable at state and local levels. Successful policymaking does not have to be mysterious; the chapter argues. The science and art of good policymaking involves identifying evidence-based options, conducting feasibility assessments, and fostering strategic partnerships. The chapter presents some critical factors for developing and implementing policy. The chapter relates these to the work in the two case studies it presents.
Overview—Training and Workforce: Preparing for the Future That Is Already Here
Authors: Michener J. Lloyd , Thomas Craig W.
Published: May 2019

Over the last few years, this chapter explains, the role of training and the workforce has moved from the position of not a primary concern to an important factor in public health issues. Part of the shift was the result of the rapid growth of community partnerships, making the opportunity to include learners more than an isolated possibility. Another was the infrequent presence of learners, training programs, or professional schools in the partnerships, even though many were occurring in the neighborhoods around the professional schools and programs. And a large part was the eagerness of the learners themselves. However, as this next section of chapters will explain, the voice of students and residents in the health improvement process has not yet reached full force.
On the Synergies That Can Generate Excellence in Public Health Education
Authors: Galea Sandro
Published: May 2019

This chapter focuses on health education in the university sector. Public health has much to benefit from the responsibility for knowledge translation by universities, the chapter argues. Ultimately, the creation of the social, economic, and political conditions that generate health must involve engagement in the tools of cultural conversation and in a full-throated engagement both in communicating these ideas to those who can make change happen and to the general public who influence them. The chapter looks at the ways that public health further education has been changing in recent years. It ends by looking forward to a time of innovation in education.
Better Together: Engaging Nursing Leaders in Community Collaborative Efforts
Authors: Tran Anh N. , Derouin Anne
Published: May 2019

This chapter focuses on the role of nurses in bringing positive changes to population health through public health collaborative efforts. The chapter questions why nurses haven't enjoyed a more prominent role in some in community public health projects. It lists some historic figures in the nursing world. The chapter concludes with a look to the evolving role of nurses now and in the future. Although professional nurses will continue to serve at the bedside of patients and families in their most vulnerable moments, they have also begun to use their advocacy and leadership skills to make positive changes and offer solutions to the challenges and choices that patients, families, and communities face in our evolving health care system.
Introduction
Authors: Ryle Cym Anthony
Published: May 2019

This chapter briefly describes the author’s background in primary care and the origins of his interest in diagnostic reasoning and error. It introduces the key themes of the book: the central role of diagnosis in medicine; the nature of diagnostic terms and classifications; the characteristics of human cognition; diagnostic reasoning; common types of diagnostic error; the implications for patient safety; the potential for changes in education, postgraduate medical training, and clinical practice to reduce diagnostic error; and possible obstacles to the implementation of the proposed changes. Also addressed is actual clinical encounters and how they are addressed by new clinicians and experienced physicians.
Probability in Diagnostic Thinking
Authors: Ryle Cym Anthony
Published: May 2019

This chapter observes that diagnostic reasoning involves both informal and mathematical estimates of probability. It argues that intuitive estimates of the likelihood of disease are necessary in the early phases of the diagnostic process but notoriously inaccurate. It notes that formal calculations are not possible when the question is, What might be wrong with this person? but are much more accurate than intuition in estimating the probability that a specific disease is present. The chapter suggests that population-based calculations of the likelihood of disease may lead clinicians to play Russian roulette by proxy because individual variation and individual risk factors may alter that risk in a given patient. It refers to evidence that many clinicians are inexpert in statistical methods. The chapter describes some basic statistical processes and their place in the clinical application of test results. It discusses the necessity and challenges of managing patients whose symptoms are medically unexplained.
Thrombosis
Authors: Verheugt Freek
Published: May 2019

Blood coagulation plays a role in the pathogenesis of acute and chronic vascular disease. Acute myocardial infarction is generally associated with partial or complete thrombotic occlusion of one of the coronary arteries, whereas embolic stroke usually is associated with clot formation in the left atrium, left ventricle, or carotid arteries. Arteries in the lower extremities may get occluded by thrombosis, leading to ischaemia or amputation. Finally, venous thromboembolism is mainly caused by thrombus formation in the veins of the pelvis and/or the legs. This chapter deals with the effectiveness and safety of antiplatelet and anticoagulant drugs in primary and secondary prevention of cardiovascular disease.
Acute coronary syndrome: STEMI and NSTEMI
Authors: Prasad Abhiram , Raphael Claire
Published: May 2019

Management of acute coronary syndrome (ACS) is dictated by clinical features and electrocardiographic findings. Morphine is used for pain relief. Sublingual or intravenous nitrates are administered to relieve ischaemia. Patients should be loaded with dual antiplatelet medications, usually aspirin and one of clopidogrel, prasugrel, or ticagrelor. For ST-segment elevation myocardial infarction, reperfusion therapy is with primary percutaneous coronary intervention (PPCI) or thrombolysis for those presenting to non-PPCI centres who cannot have timely access to PPCI. For non-ST-segment elevation myocardial infarction and unstable angina, timing of angiography, and revascularization if indicated, is determined by the severity of ischaemia. All patients with ACS should be treated with secondary prevention medications, including antiplatelet therapy, statins, beta-blockers, and renin–angiotensin system inhibitors.
Atrial fibrillation
Authors: Dan Gheorghe-Andrei , Steffel Jan
Published: May 2019

Atrial fibrillation (AF) is the commonest cardiac arrhythmia in hopspitalized patients, with an increasing incidence with age and an epidemic increase projected for the next 10 years. Therapy of AF has several goals: to decrease mortality (mainly due to cardiovascular diseases), stroke rate, ventricular deterioration and heart failure, cognitive impairment, and dementia, as well as to increase quality of life. The recent European AF guidelines specify the management strategies for each of the above-mentioned goals. For stroke prevention, treatment with a non-vitamin K antagonist oral anticoagulant (NOAC) has emerged as the therapy of choice for the majority of patients with AF in the absence of rheumatic mitral disease and mechanical valve prostheses. However, in daily use of these drugs, many challenges remain that healthcare providers need to be aware of. Regarding treatment of the arrhythmia itself, it remains a therapy addressing the quality of life. Catheter ablation has emerged as a valid alternative for a variety of patients. Nevertheless, pharmacological antiarrhythmic drug therapy remains an important pillar for the majority of patients, and effective and safe use implies an important skill for every cardiologist.
Myocarditis and pericardial syndromes
Authors: Boffa Giovanni , Ceconi Claudio
Published: May 2019

Myocarditis is defined as inflammatory disease of the myocardium, diagnosed by established histological, immunological, and immunohistochemical criteria. Aetiology-targeted therapy is indicated when supported by evidence. However, in the vast majority of patients with myocarditis, the most important targets of treatment are heart failure and arrhythmias. Management of systolic left ventricular (LV) dysfunction should follow the recommendations of current European Society of Cardiology guidelines on heart failure. Immunosuppression is indicated only in giant cell myocarditis. In patients with severe LV dysfunction, inotropic support may be necessary and ventricular assist devices may represent a bridge to recovery or to heart transplantation There are no specific treatments of arrhythmias in myocarditis. Implantation of cardioverter–defibrillators must be deferred in the acute phase. In patients with severe ventricular arrhythmia, a wearable cardioverter–defibrillator can represent a bridge to recovery, implantation of cardioverter–defibrillators, or heart transplantation. Pericardial diseases may be either an isolated disease or part of a systemic disease. The main pericardial syndromes that are encountered in clinical practice include pericarditis (acute, subacute, chronic, and recurrent), pericardial effusion, cardiac tamponade, and constrictive pericarditis, and pericardial masses. Major advances have occurred in therapy with the first multicentre randomized clinical trials. Colchicine has been demonstrated as a first-line drug to be added to conventional anti-inflammatory therapies in patients with a first episode of pericarditis or recurrences, in order to improve response to therapy, increase remission rates, and reduce recurrences.
Kidney disease
Authors: Banerjee Debasish , Ramphul Robin , Goldsmith David
Published: May 2019

The cardiovascular disease profile in patients with chronic kidney disease, and liver disease and during pregnancy is different from that in the general population. Due to altered physiology in these conditions, drug handling is different. Hence, drug therapies in these conditions are described separately in this section. Cardiovascular disease is the commonest cause of morbidity and mortality in patients with chronic kidney disease. Yet drug therapy is often withheld or used in inappropriate doses. The kidneys have a major role in the pharmacokinetics of numerous drugs, and hence the renal function determines the dose and effect of these drugs. This chapter describes common cardiovascular events in chronic kidney disease patients and appropriate drug therapy. Evidence-based guidance is provided when appropriate, and the dose adjustments are as known, when available, in accordance to the current European Society of Cardiology guidelines.
Cardiovascular drugs—from A to Z
Authors: Tamargo Juan , Caballero Ricardo , Delpón Eva
Published: May 2019

Cardiovascular drugs from A to Z.
DNA repair and genome integrity
Authors: Buscemi Giacomo
Published: May 2019

The DNA damage response (DDR) is a complex network of pathways involving hundreds of proteins with the main goal to detect and fix lesions occurring to DNA structure, thus preserving genome stability throughout generations. To enhance repair efficiency and eventually clear unrepaired harmful cells, the DDR has under its own control the progression of cell cycle, the induction of cellular senescence and the apoptotic programme. Furthermore, cells take advantage of DDR to manage break-like structures, such as telomeres, and to check processes involving DNA ‘cut and paste’ steps like meiosis and immune response. Since all these aspects of a cell life are frequently altered in cancer, not unexpectedly, deregulation of DDR is an essential step during carcinogenesis. Indeed, even if mutations in DDR genes partially reduce the repair ability of a precancerous cell, they also enhance the possibility of oncogene mutation, allow hyper-replication and promote cell survival and adaptation in stressed conditions. On the other side, impairment of DNA repair sensitizes cancer cells to radio and chemotherapeutic agents inducing DNA damage and DDR components are promising targets to enhance therapy efficiency.
Viral carcinogenesis
Authors: Dittmer Dirk P. , Damania Blossom
Published: May 2019

Between 20 and 30% of human cancers are caused by infectious agents. These can be multicellular parasites, bacteria, or viruses. Whereas bacteria and parasites cause cancer by indirect mechanisms, such as inflammation and immune deregulation, viruses infect human cells directly and initiate molecular changes that lead to uncontrolled proliferation. Both DNA and RNA viruses, such as retroviruses, can cause cancer; however, the ability to promote cancer is a by-product of viral evolution and a low frequency event, often the result of faulty virus replication. Most human oncogenes, such as MYC, SRC, RAS, were first discovered because they had been pirated by retroviruses. The function of key human tumour suppressor proteins, such as RB and TP53, were identified because they bind to and are inactivated by DNA tumour viruses. Because viruses are foreign, vaccines can be devised that target them. More recently it has become possible to prevent two types of cancer caused by viruses—cervical cancer caused by human papillomavirus (HPV) and hepatocarcinoma caused by hepatitis B virus (HBV)—by preventing the initial infection using vaccination. Study of the relationship between infective agents and cancer has therefore achieved two main goals: to unravel basic mechanisms of carcinogenesis and to make some cancers preventable.
Growth factors and associated signalling pathways in tumour progression and in cancer treatment
Authors: Gaborit Nadège , Yarden Yosef
Published: May 2019

To gain increased proliferation, blood supply, invasiveness, and resistance to cytotoxic treatments, cancer cells continuously secrete polypeptide growth factors, or they utilize factors produced by the associated normal tissue and the immunological microenvironment. The growth factors relay biochemical messages by binding with receptor tyrosine kinases (RTKs) located at the cell surface. In response to activation and receptor auto-phosphorylation, RTKs mobilize diverse signalling pathways, which culminate in cytoplasmic and nuclear alterations, including activation of gene expression programmes. This chapter describes several well-characterized growth factors, highlights the cognate receptors and downstream signalling pathways, and exemplifies involvement of specific growth factors in maintenance of the hallmarks of cancer. An account of clinically approved drugs able to intercept growth factor signalling closes this chapter.
Oncogenesis and tumour suppression
Authors: Tavassoli Mahvash , Pezzella Francesco
Published: May 2019

Two sets of genes are among the major driver of tumours, both malignant and benign: the oncogenes and the tumour suppressor genes. Oncogene refers to a gene that encodes for a protein (oncoprotein) in which excessive and unregulated activity can transform a normal cell into a cancer cell. As it is necessary for just one of the two gene copies to be abnormal, oncogenesis is defined as dominant. Tumour suppressor genes are known for their roles in inhibiting cell growth and have antitumour effects. According to the classic model, growth suppressor genes are recessive and therefore both copies have to be inactivated in order for an effect to be seen. Exception however occurs! Recently also non-coding mRNAs (i.e. an mRNA that is not translated into a protein) have been found to be able to induce oncogenic and suppressive effects. Finally, both some genes and some non-coding mRNA are able, in certain cellular contexts, to behave both as both an oncogenic and a suppressive factor.
The signalling pathways in cancer
Authors: Hu Jiangting , Pezzella Francesco
Published: May 2019

The signalling pathways allow communication between the outside world and the cell: for this very reason they are also known as ‘environmental information processing’ pathways. Signalling pathways are made up by many different types of molecules which work together to control one or more cell functions in response to a given stimulus. The first part of the chapter will deal with the general principles, types of signals received by the cell, the receptors available, and how they transmit the signals to the downstream components. In the second part, we will present the basic ‘anatomy’ of these pathways and their main roles in cancer.
Telomerase and immortalization
Authors: Collopy Laura , Tomita Kazunori
Published: May 2019

The lifetime of a cell is set by the terminal ends of our chromosomes, ageing timers called telomeres. Most dividing cells, not exceptional for cancers, require telomeres to protect chromosomes. However, telomere erosion occurs at every cell cycle, thus imposing a proliferative capacity, eventually triggering a growth arrest. Cancer cells must overcome this proliferative limit in order to continue dividing. In the vast majority of cases, the growth and progression of cancers correlates with the upregulation of telomerase, an enzyme that replenishes telomeres. Telomerase is not active in normal, differentiated cells and its reactivation in cancer renders cells immortal and promotes their continued growth and development. Curiously, in cancer telomerase maintains short telomeres, retaining chromosome instability. Here, we briefly take you through history of cellular mortality with the connection to telomeres and telomerase and review their function in the normal cell to address their role during the transformation to malignancy.
Cancer immunology
Authors: Waldmann Herman
Published: May 2019

Until recently, the prospects for harnessing immune mechanisms to fight cancer were not encouraging. The advent of monoclonal antibodies, both as diagnostics and as probes for molecular function, have been important, while the identification of dendritic cells as a major intermediary between the antigen source and T-cell activation has been crucial. Major advances in molecular biology and the creation of mutant mice lacking defined gene products have pinpointed key molecules influencing immune function. Finally, many translational efforts in vaccination, autoimmune disease, and transplantation have enabled identification of hitherto undervalued mechanisms that the immune system uses to regulate itself. A fuller understanding of self-tolerance mechanisms, tumour antigens, and the tumour microenvironment has catalysed a wide range of novel therapeutic strategies and has also allowed a re-evaluation of mechanisms underlying the benefits of past chemotherapies.
Cancer systems biology: From molecular profiles to pathways, signalling networks, and therapeutic vulnerabilities
Authors: Verbeke Lieven , Van Laere Steven
Published: May 2019

Cancer systems biology encompasses the application of systems biology approaches to cancer research. Historically, systems biology was first applied in cancer research to enable a pathway-oriented interpretation of gene expression data and this strategy has undoubtedly delivered relevant insights with respect to many aspects of cancer biology. Nowadays, cancer is regarded as a complex system that integrates signals from different levels (i.e. (epi)genomics, transcriptomics, micro-environment) through a network of interconnected proteins to generate a biological response. This holistic approach not only allows the identification of new and relevant signal transduction pathways, but also provides a better understanding of several key properties of cancer cells that can be best understood from a network-level perspective: robustness, evolvability, and plasticity. This chapter provides an overview of several key concepts of systems biology, including reference gene set libraries, network topology, and available strategies to establish biological networks. Next, these concepts are utilized to explain gene set and gene network analysis with particular focus on cancer biology. Finally, the caveats and challenges that are facing cancer systems biology are summarized.
Immunotherapy and tumour resistance to immune-mediated control and elimination
Authors: Monnot Gwennaëlle C. , Romero Pedro
Published: May 2019

The field of tumour immunology has gradually reached a consensus that the immune system and tumours sustain a rich set of dynamic interactions starting early during carcinogenesis. Incipient tumours may be eliminated by the immune system via adaptive immune responses mediated mainly by cytotoxic CD8 T lymphocytes, which recognize short antigenic peptides presented by polymorphic major histocompatibility complex (MHC) class I molecules. Advanced tumours, however, are generally highly resistant to the main effectors of the immune system. Moreover, the molecular and cellular composition of the tumour microenvironment is strongly immunosuppressive. Recent research efforts have focused on the dissection of the mechanisms operating at the tumour sites, which neutralize antitumour immunity in both experimental models and directly in cancer patients. All along this basic research, translational scientists have tried to harness the immune system to design novel therapeutic modalities that have collectively been coined as cancer immunotherapy. The overall goal has been to increase the numbers of tumour antigen-specific T cells in cancer patients via either vaccination or adoptive transfer of large numbers of immune cells. It is safe to state that cancer immunotherapy will provide a revolution in the treatment of cancer and the future may bear the prospect of effective tumour control in many cancer types, and that immunotherapy will be one of the main components of effective therapeutic options.
The nature of diagnostic constructs
Authors: Huda Ahmed Samei
Published: May 2019

Classification is essential in medicine to help doctors acquire, learn, and recall clinically useful information about problems coming to healthcare professionals’ attention. There problems include both essentialist diagnostic constructs (where all examples share a quality and are distinct from other constructs) and nominalist diagnostic constructs (used to describe clinically useful concepts not necessarily separate from other constructs). Diagnostic constructs may be recognized using defined criteria and/or as prototypical examples. They are based on similarities in clinical picture, mechanisms/processes, and/or causes. They may be used to identify clinically important situations, diseases/clear-cut syndromes, spectrums of health, illness(es)/and condition(s), injuries, and other situations of interest to healthcare professionals. Thresholds established on the basis of clinical utility (e.g. level of distress or risk of complications) may be used to define conditions. Care must be taken to guard against over-medicalization of problems or situations.
Spectrums of health
Authors: Huda Ahmed Samei
Published: May 2019

Many conditions in psychiatry cannot be separated from normality/healthy states (e.g. depression) but even these broad diagnostic constructs may include syndromes like melancholia. There is still a debate as to whether psychotic-like experiences in the community are on a continuum with psychotic symptoms in those meeting diagnostic criteria for psychosis diagnostic constructs. Schizophrenia may exist on a continuum with related conditions (e.g. schizotypal personality disorder). There are differences between people meeting criteria for schizophrenia and healthy controls but none that can be used as a diagnostic test to separate the two, with the possible exception of anomalous self-experiences differentiating schizophrenia spectrum conditions from healthy controls and other diagnostic constructs. Several general medical conditions also exist on a continuum with health with no zones of rarity (e.g. hypertension and type 2 diabetes). Thresholds to meet criteria for these diagnostic constructs are chosen by expert committees often based on risk of developing complications (e.g. myocardial infarctions) and/or whether medical intervention may be beneficial. Even reasonably objective investigations can give abnormal results in healthy people. Concerns about whether thresholds are too low, leading to over-diagnosis, unnecessary treatment, and iatrogenic harm, also exist in general medicine. Other classifications in mental health will need to use thresholds in order to fulfil functions such as administration, research, or access to services. Dimensional classifications are good at representing the many spectrums of mental health.
Spectrums of conditions
Authors: Huda Ahmed Samei
Published: May 2019

Psychiatric diagnostic constructs often have no zones of rarity between different diagnostic constructs, and they often co-occur. This happens even where clear disease processes are involved, such as the dementias. They may represent different areas of a spectrum of illness/condition and/or be part of a spectrum of illnesses/conditions. However, they share both these characteristics with many general medical diagnostic constructs. For spectrums of illness/condition this may be because there are no natural boundaries but that it is important or seems obvious to recognize different areas of the spectrum for reasons of clinical utility (such as different prognostic implications or treatments) or different clinical pictures. For spectrums of illnesses/conditions the reason for co-occurrence may be because different diagnostic constructs have similar causes/mechanisms. On the other hand, these problems of lack of boundaries are not present as commonly in general medical diagnostic constructs. Alternative mental health classifications do not have the same issues with co-occurrence. They may be more useful in research to discover reasons why co-occurrence of symptoms may occur but have pragmatic drawbacks for other classification functions.
Treatments in psychiatry compared to general medicine
Authors: Huda Ahmed Samei
Published: May 2019

There is clear overlap in effectiveness between psychiatric treatments and general medicine medications. Both psychiatric treatments and general medicine medications can be harmful. Mechanisms of action of psychiatric treatments are often obscure or unknown. This is less common in general medicine medication but some of the most commonly prescribed drugs used in general medicine do not cure or act directly on disease mechanisms. Evidence-based psychotherapy is an effective treatment for many mental health conditions; its relative effectiveness compared to psychiatric medication varies depending on the condition. If the client is willing and able to participate in bona fide psychotherapy with evidence of effectiveness, it may be preferable to psychiatric medication as it seems to have less serious adverse effects although more research is needed on harmful adverse effects. Psychotherapy combined with medication is often more effective than either used alone and both types of treatment are complementary, even synergistic, in achieving treatment objectives. Access to psychotherapy is often less easy than access to medication as it is labour intensive, and using medication allows doctors to see many more patients (see Chapter 5). For some conditions and situations, for example, for those unable to participate in psychotherapy, psychiatric treatments are still preferred.
Final conclusions
Authors: Huda Ahmed Samei
Published: May 2019

The medical model in mental health uses diagnostic constructs with attached useful information (e.g. on prognosis or response to treatments) that often identifies areas of spectrums rather than diseases or syndromes. Diagnostic constructs in psychiatry and general medicine overlap for attributes such as clinical utility (e.g. predicting likely outcomes), validity (e.g. whether boundaries exist between different diagnostic constructs), and importance of social factors. There is an overlap in effectiveness between psychiatric and general medicine treatments, and many general medicine medications do not reverse disease processes. Describing the nature of diagnostic constructs can be done by describing the basis of classification and nature of the classified condition. Different mental health classifications have particular strengths and weaknesses for clinical, research, and social functions. Research in mental health may need classifications other than diagnosis to improve understanding of causes and mechanisms and also to develop better diagnostic constructs. As doctors in all specialties will encounter mental health problems there will always be psychiatric diagnostic constructs compatible with their training. The medical model of mental health allows doctors to assess and offer effective treatments to large numbers of patients and provide emergency cover. Mental health research and service provision will always need to address psychosocial issues.
Detecting the first signs of emerging psychosis
Authors: Schultze-Lutter Frauke
Published: May 2019

Psychotic disorders are costly and debilitating illnesses. Their prodromal phase usually lasts several years and offers opportunities for indicated prevention. Currently, two risk-detection approaches, developed in adult samples, are typically followed: ultra-high risk (UHR) criteria, developed to predict first-episode psychoses within 12 months; and basic symptom (BS) criteria, aimed at the earliest possible detection of emerging psychoses. The main UHR criterion is defined by attenuated psychotic symptoms, which resemble positive symptoms of psychosis except that some insight into their abnormal nature remains. In contrast, BS criteria include subtle disturbances in information processing, experienced immediately with full insight. Various studies have indicated that using a combination of both approaches might increase sensitivity and support the development of a timely, change-sensitive, and stratified risk-detection method. However, since age might play an important role, both the UHR and BS approach might be less psychosis-predictive and less clinically relevant in children and adolescents.
Are ethnic differences in pathways to care for psychosis in England reducing?
Authors: Oduola Sherifat , Morgan Craig , Craig Tom K.J.
Published: May 2019

Studies in the 1990s showed that, compared with the majority populations, people from minority ethnic groups in England were more likely to access psychiatric care via crisis routes. This chapter, and the studies it is based on, explore whether this adverse pattern continues. The authors analysed data from two population-based studies of first-episode psychosis (FEP) carried out 15 years apart. Participants for the studies were 193 FEP patients, aged 18–35 years, presenting to psychiatric care in South London between 1997 and 1999, and 265 FEP patients presenting in 2010–2012. The outcome measure was source of referral during first-episode psychosis. Results of the studies showed that, compared with 15 years ago, ethnic differences were not evident for police or GP involvement. However, ethnic minorities were more likely to access care via accident and emergency departments (Black Caribbean: adj. OR = 48.89; 95% CI = 3.49–684.71; Black African: adj. OR = 7.34; 95% CI = 1.15–46.74). It seems, from these results, that the disparities in pathways to care appear to be narrowing. This may be explained by changing socioeconomic factors and family involvement.
Experiences and lessons from the Singapore Early Psychosis Intervention Programme
Authors: Verma Swapna K. , Yin Poon Lye , Lee Helen , Ann Chong Siow
Published: May 2019

The long duration of untreated psychosis (DUP) and probable severe consequences were the impetus for establishing the Early Psychosis Intervention Programme (EPIP) in Singapore in the year 2001. EPIP is a comprehensive, integrated, patient-centred programme which aims to improve the outcome of patients with first-episode psychosis through public awareness and destigmatization initiatives, collaboration with community services, and provision of early engagement and phase-specific care of those with psychosis. In April 2007, the Singapore Ministry of Health launched its first ever National Mental Health Blueprint, and several community-based services were developed to improve mental healthcare and strengthen early detection and prevention of mental illnesses. The Blueprint thus provided the opportunity for the EPIP to strengthen its early intervention efforts beyond psychosis. This chapter discusses the role of the Community Health Assessment Team (CHAT) which is more broad-based, focusing on promoting awareness of youth mental health issues and encouraging this sector of the population to seek help early.
From principles to practice
Authors: Scott Jan
Published: May 2019

The main goals of early intervention in psychosis (EIP) are to reduce the time period between the onset of psychosis and the commencement of effective treatment, and to provide consistent and comprehensive care during the critical early years of illness. In this chapter, each element of the EIP template is examined from the perspective of bipolar disorders (BD) to determine whether the core concepts that underpin EIP can be translated to the early identification and treatment of BD. Findings from research on the duration of untreated bipolar (DUB) are explored, and evidence for a ‘bipolar at-risk’ (BAR) syndrome is reviewed. Research is reported on the prediction of transition from at-risk states to full syndromal BD in young persons in the peak age range for the onset of severe mental disorders. Finally, the chapter briefly discusses ongoing research on high-benefit, low-risk interventions that have been offered to individuals with emerging BD during adolescence or early adulthood.
Early intervention in bipolar disorders
Authors: Malhi Gin S. , Morris Grace , Hamilton Amber , Outhred Tim
Published: May 2019

The concept of early intervention for bipolar disorder (BD) is both attractive and logical as there is often a considerable delay between the onset of BD symptoms and diagnosis. This chapter addresses key definitional and conceptual considerations for early intervention in BD and exposes the expansive gaps in our knowledge of the phenomenology of BD, prognostication, and disease progression and trajectory. These gaps highlight that early intervention for BD—in terms of treatment specificity and timing—is far from being realised. There are though significant risks associated with implementing early intervention strategies at this stage, which may range from unnecessarily prescribing potentially harmful medication to perhaps inadvertently accelerating the progression of the illness. Until there are major scientific and clinical advancements, this chapter provides a conservative yet involved approach for early intervention in BD.
Introduction
Authors: Davies Andrew
Published: May 2019

Breakthrough pain is a transient exacerbation of pain that occurs despite relatively stable and adequately controlled background pain. Breakthrough pain is a common and heterogeneous condition. It is a significant cause of morbidity. The focus of this book is on cancer-related breakthrough pain in adults. Background pain refers to ‘constant or continuous pain of long duration’. However, breakthrough pain has been described as: ‘a transient exacerbation of pain that occurs either spontaneously, or in relation to a specific predictable or unpredictable trigger, despite relatively stable and adequately controlled background pain’. It can be spontaneous or incident related and is common in cancer patients, with around 60% being affected. Breakthrough pain is a major challenge to healthcare professionals (as well as to their patients).
Non-opioid analgesics
Authors: Davies Andrew
Published: May 2019

Breakthrough pain is a heterogeneous condition. Non-opioid analgesics are a diverse group of drugs. Non-opioid analgesics may have a role in the management of breakthrough pain. Data on the use of most non-opioid analgesics is limited. Paracetamol and non-steroidal anti-inflammatory drugs are generally used as around-the-clock medication, although they may also be used as rescue medication. Systematic reviews of oral NSAIDs have confirmed benefits in cancer pain. Midazolam has been used in the treatment of refractory incident pain secondary to bone metastases and there is the potential for its use in the management of breakthrough pain secondary to muscle spasm. Ketamine is employed in anaesthetic doses in the management of procedural pain and in the management of predominantly non-malignant breakthrough pain. There is conflicting evidence for the use of nitrous oxide in the management of breakthrough pain.
The effects of Arabidopsis genome duplication on the chromatin organization and transcriptional regulation
Authors: Zhang Hui , Zheng Ruiqin , Wang Yunlong , Zhang Yu , Hong Ping , Fang Yaping , Li Guoliang , Fang Yuda
Published: May 2019

Autopolyploidy is widespread in higher plants and important for agricultural yield and quality. However, the effects of genome duplication on the chromatin organization and transcriptional regulation are largely unknown in plants. Using High-throughput Chromosome Conformation Capture (Hi-C), we showed that autotetraploid Arabidopsis presented more inter-chromosomal interactions and fewer short-range chromatin interactions compared with its diploid progenitor. In addition, genome duplication contributed to the switching of some loose and compact structure domains with altered H3K4me3 and H3K27me3 histone modification status. 539 genes were identified with altered transcriptions and chromatin interactions in autotetraploid Arabidopsis. Especially, we found that genome duplication changed chromatin looping and H3K27me3 histone modification in Flowering Locus C. We propose that genome doubling modulates the transcription genome-wide by changed chromatin interactions and at the specific locus by altered chromatin loops and histone modifications.
Barbara Johnson
Authors: Valens Keja
Published: May 2019

Barbara Johnson (b. 1947–d. 2009) bridged the heyday of deconstruction and the turn to theory in the 1970s and the ascendance of cultural studies and the turn to ethics in the early 21st century. As Johnson moved the insights of deconstruction into areas such as feminisms, African-American studies, and cultural studies, her attention to “differences within” engaged not only language and rhetoric but also politics, popular culture, and the power of differentiation to both oppress and express particular subjects. Johnson’s career, cut short by a neurodegenerative disease, is framed by her work in translation of Derrida’s Dissemination at the beginning of her career and Mallarmé’s Divagations toward its end. She cast her critical and theoretical project as the translation of structuralism and poststructuralism into literary insight, a process that is easily recognizable in her most anthologized, reprinted, and oft-cited essays, “The Frame of Reference,” “Melville’s Fist,” “Apostrophe, Animation, and Abortion,” and “Metaphor, Metonymy, and Voice in Their Eyes Were Watching God.” Johnson’s work transports critical frames and moves across a variety of genres and fields, from psychoanalysis to law and from Romanticism to 20th-century American popular culture. Her unparalleled readings—of words, concepts, stories, poems—examine how texts do, and undo, what they say. In the process, Johnson’s writing playfully and often surprisingly displaces authority (even her own) to reveal the poetic and political work of multivalence. The wide range of anthologies that include essays by Johnson attest to the tremendous scope of her work and to the difficulty of summarizing even where its major contributions lie.
Philosophy of Computer Science
Authors: Turner Raymond
Published: May 2019

The subject matter of computer science encompasses a large number of different activities that range from abstract mathematical topics through core engineering practices and scientific investigations. Subsequently, the philosophy of computer science overlaps with the philosophies of mathematics, science, and technology, and the central philosophical concerns of these disciplines all have computational analogues. The ontological status of programs, the nature of computational abstraction, and the kind of knowledge delivered by correctness proofs are central instances. In addition, because of the focus of computer science on formal languages and their semantic interpretation, the philosophy of computer science draws in topics and inspiration from the philosophies of language and mind.
Antonio Pucci
Authors: Predelli Maria Bendinelli
Published: May 2019

Leaving aside Dante, Petrarch, and Boccaccio—the three exceptional figures of the Italian Trecento—Antonio Pucci (b. c. 1310–d. 1388) is perhaps the most notable writer of the literary Florentine landscape of that period. His abundant production includes an astonishing variety of genres and themes and reveals his alertness in tuning in with new trends in literary expression; his language is fascinating for its richness and spontaneity, and for its proximity to the oral means of communication; and his temperament reveals a passionate connection to the political and social aspects of his city. The scholars of the late 1800s studied and appreciated Pucci as a “popular” writer, one that expressed in simple and sincere ways the sentiments of the Florentine middle and lower classes, commonly pointing out, however, the poverty of his style and his absence from the incipient humanist revolution. In his overview of autobiographical, gnomic, political, and popular poetry (Critica 29 [1931]: 241–263), Benedetto Croce (followed by later critics) presented him as a popular journalist, thinking no doubt of the serventesi in which he narrated and commented the major events that marked the life of the Commune (e.g., the flood of 1333, the rise and fall of a seigneurial regime, various episodes of the war between Florence and Pisa, the plague of 1348). Over the last hundred years, a number of scholars have paid greater attention to his writings, collecting anthologies of his lyrics and providing editions of single works. Interestingly enough, some critical editions (Le Noie, Contrasto delle donne, Sonnets) were first produced in the United States in the first half of the 20th century. This critical attention also enhanced Pucci’s cultural status: scholars began to gather evidence of Pucci’s familiarity with Boccaccio, and highlighted his important role as a mediator between elite and popular culture. New editions of his cantari appeared, and new works were more or less persuasively attributed to him. More recently, Pucci’s writings have also been taken into account to explore issues related to gender studies, particularly in North America. To delve into Pucci’s writings, and correctly circumscribe them, a great portion of the research has been devoted to manuscript studies. The last section to this bibliography also includes a few items concerning the ways and milieux in which Pucci’s name and works persisted in the century after his death. Bibliographical items of the 18th, 19th, and early 20th centuries are only exceptionally listed in this article, as they can be found in Speight 1954, cited under Bibliographies and Other Research Tools.
Hymns
Authors: Salisbury Matthew Cheung
Published: May 2019

Although its functional origin as a liturgical practice may be linked to the psalms, readings, and prayers of Jewish synagogue worship around the time of Christ, the history of medieval hymnody is, in the main, the history of Christian Latin poetry. Influenced first by early hymn-writers’ education in classical grammar and rhetoric, the hymn quickly assumed the role assigned it by Augustine: “the praise of God, when sung,” framed broadly at first, and then acquiring typical habits of meter and rhyme and a specific liturgical function. Poetic texts penned by early Christian authors attained fame and were assumed into collective liturgical practice. They were joined by newly-written medieval hymns, constructed with the liturgical context in mind and often written for a particular occasion (i.e., the liturgical observance of a saint’s day). Some later medieval Latin poetry served more overtly devotional purposes. The earliest extant Latin hymns were written by Ambrose of Milan in the 4th century. These, together with others, were incorporated into the structures of liturgy set out by the architects of monastic life, including Saint Benedict. Other “hymns” were drawn from sacred Latin poetry in longer form and from across the Christian West, and many more were written through the Carolingian Renaissance. Even more hymns were written for specific occasions in the liturgical calendar up to the end of the Middle Ages, many anonymous but some written by literary luminaries such as Peter Abelard and Thomas Aquinas. These proper hymns replaced those of the day or of the relevant portion of the Common of Saints. By Augustine’s definition, hymns are sung praises, but relatively little work has been done on the music to which the much more extensively studied texts are sung. This may be a consequence of two factors. First, the melodies were broadly interchangeable, since the texts had been written in a limited number of meters. Second, they tended to vary quite considerably. Hiley’s Western Plainchant: A handbook (Oxford: Oxford University Press, 1993) suggests that thirty or fewer hymns were sung to the same melodies across the whole of Europe. They do not always correspond to the conventions of other liturgical melodies in terms of structure, cadence, or text-setting, making them difficult to compare with the chants for other genres.