bluuebunny/crossref_metadata_2025 huggingface dataset:
When Less Is More
Authors: Walsh Richard A.
Published: November 2017

The natural history of PD produces a predominance of nonmotor complications in the later years that can often be more disabling than the motor complications due to their impact on quality of life. Quality of life is less impaired by motor symptoms than it is by cognitive impairment, hallucinations, autonomic involvement, and sleep disruption. Carer burden can be significant, and a shift of emphasis toward maximizing quality of life for patient and carer over the achievement of continuous dopaminergic stimulation is required. Recognition of the carer burden is an important facet of the palliative neurology consultation, which should target resources to limit carer burnout in recognition of their critical role.
“I Am Not Sure If I Should Do DaT”
Authors: Walsh Richard A.
Published: November 2017

Nuclear medicine-based imaging techniques can provide an estimation of nigrostriatal tract denervation based on radionucleotide uptake in the distal presynaptic terminals of dopaminergic neurons. Although unhelpful in differentiating between differing etiologies of denervation in varied neurodegenerative disorders associated with parkinsonism, this imaging is justified in situations in which parkinsonism is believed to be drug-induced or functional or in cases in which subclinical parkinsonism is suspected. The most common clinical situation in which dopamine transporter imaging is helpful is in the patient on neuroleptic therapy that cannot be stopped who has developed parkinsonism. Dopamine transporter imaging should be normal in drug-induced tremor.
Parkinson’s Disease or Essential Tremor?
Authors: Walsh Richard A.
Published: November 2017

Fragile X-associated tremor ataxia syndrome is a heredodegenerative syndrome that presents in older men as a tremor syndrome with less prominent ataxia and cognitive impairment initially. The underlying genetic cause, a premutation in the FMR1 gene, results in a toxic accumulation of mRNA. The full mutation, a triple-repeat expansion of more than 200 CGG repeats, gives rise to a reduction in FMR1 protein expression and fragile X, a neurodevelopmental disorder that may be identified in successive male generations. The prevalence of carrier status is high in the general population, and it is likely that most movement disorders clinics will have one or more patients with this syndrome, potentially carrying a label of essential tremor.
Seizures and Shakes
Authors: Fox Susan H.
Published: November 2017

Wilson’s disease is an autosomal recessive, treatable heredodegenerative disorder characterized by excessive deposition of copper in the liver, brain, and other tissues including the kidneys, pancreas, and joints. Early recognition of the disorder, which can present with a variety of movement disorders and neuropsychiatric phenomena, is critical to avoid irreversible end organ damage through the initiation of copper chelating agents. Diagnosis relies first on demonstrating evidence of brain iron deposition on magnetic resonance imaging of brain and elevated urinary copper excretion in the appropriate clinical context. Genetic testing for mutations in the ATP7B gene will identify a mutation in up to 90% of cases.
Delayed and Often Persistent
Authors: Fox Susan H.
Published: November 2017

Tardive syndromes are drug-induced hyperkinetic movement disorders that occur as a consequence of dopamine D2 receptor antagonism/blockade. There are several types, including classical tardive dyskinesia, tardive dystonia, tardive tics, tardive myoclonus, and tardive tremor, and it is important to the management of these disorders that the type of movement disorder induced is identified. Tardive syndromes can occur with all antipsychotic drugs, including so-called atypical drugs. Patients taking these drugs should be evaluated frequently for side effects. Evaluating the nature of the movement (i.e., chorea or dystonia) is important because treatment options can differ according to the type of dyskinesia present.
The Stand-Alone Tremor
Authors: de Bie Robertus M. A.
Published: November 2017

Essential tremor is defined as long-standing bilateral hand/arm tremor that is visible and may occur persistently during posture-holding, simple movements, and action. The tremor may be slightly asymmetrical. Other areas of the body that may be affected are head and neck (most frequently), the voice, and legs. Head tremor without limb tremor is accepted as essential tremor, although this definition remains controversial. Essential tremor is a progressive disease and manifests at any age. Tremor in Parkinson’s disease mostly starts unilaterally. A no–no or yes–yes tremor of the head indicates essential tremor, whereas a tremor of the jaw or tongue fits with Parkinson’s disease. The cogwheel phenomenon may also occur in patients with essential tremor. Toxins and medications as the cause for postural/kinetic tremor must be ruled out. Pharmacological options for essential tremor can be unsatisfactory.
“She Is So Fidgety”
Authors: de Bie Robertus M. A. , Ten Holter Susanne E. M.
Published: November 2017

Chorea manifests as involuntary, often contnuous, unpredictable, and involuntary dance-like movements. Patients with chorea are often unaware that they have involuntary movements. Others may try to incorporate the movement into a semipurposeful action (parakinesia). Chorea is usually worse with mental activity or emotion. Physical activity may also exacerbate chorea. The presence of “motor impersistence” is typical of chorea. Sometimes patients can also make unintentional sounds referred to as hyperkinetic dysarthria. Chorea disappears during sleep. Ballism is considered a type of chorea with a more proximal distribution and larger movements. Athetosis is a term formally used for chorea with slow writing movements in the distal limbs, but it is not considered a specific entity of chorea anymore. The most important genetic cause of chorea in adulthood is Huntington’s disease, and genetic testing should be considered as a first step in all patients with adult-onset chorea if no secondary cause is found.
“It Has to Be Functional!”
Authors: Walsh Richard A.
Published: November 2017

The paroxysmal dyskinesias are a heterogeneous group of rare movement disorders, characterized by the abrupt onset of involuntary hyperkinetic movements with or without trigger factors and of variable duration. Interictal periods are marked by relative normality, although there is evidence for an association between some genotypes and migraine, episodic ataxia, and seizure disorders. Three genes have been identified that are associated with the three most common syndromes; however, these do not account for some cases with an otherwise typical history. The clinical phenotype continues to evolve with increasing characterization of genetically proven cases. Paroxysmal kinesigenic dyskinesia responds well to carbamazepine therapy.
A Rapidly Progressive Movement Disorder
Authors: Fox Susan H. , Picillo Marina
Published: November 2017

Prion diseases are a rare group of transmissible and untreatable encephalopathies that ultimately result in death after a short and rapidly progressive illness. The clinical features are variable but share a mix of cortical and subcortical features and a tendency for worsening at a speed that is typically faster than the monthly or yearly change seen in degenerative forms of dementia. Movement disorders represent a prominent feature of prion diseases and include cerebellar and extrapyramidal symptoms. Myoclonus is by far the most common involuntary movement in prion diseases. An awareness of the diagnosis is important to avoid the risk of iatrogenic transmission and to allow a discussion about prognosis with family and relatives.
An Iatrogenic Catatonia
Authors: de Bie Robertus M. A.
Published: November 2017

Neuroleptic malignant syndrome is an iatrogenic movement disorders emergency characterized by rigidity, altered consciousness, and autonomic instability of varying degrees of severity. In severe cases this can be a fatal syndrome, so recognition and withdrawal of potentially causative medications is the priority. Management is otherwise supportive, and some patients will require admission to an intensive care unit. Creatine phosphokinase can be used to monitor the disease course; a decreasing creatine phosphokinase level with an increasing temperature may indicate an infection. The incidence of neuroleptic malignant syndrome has declined considerably with the increased use of atypical neuroleptics with greater D2 receptor blockade compared to older agents.
In the Beginning
Authors: Aminoff Michael J.
Published: November 2017

Charles Bell was born in November 1774 in Fountainbridge, a suburb of Edinburgh. The city of Edinburgh at the end of the eighteenth century is described and an account is provided of the history of medical education at the University of Edinburgh and at the several non-university schools in the city. The family background of Charles Bell is discussed, as is his childhood, education, and training as a surgeon and anatomist; his first books as author and illustrator; his relations especially with his brother John, a celebrated surgeon and anatomist; and his departure from Edinburgh in 1804.
London and the Great Windmill Street School
Authors: Aminoff Michael J.
Published: November 2017

Charles Bell’s arrival in London in 1804 and interactions with various prominent surgeons are discussed. The existing medical educational system is described, including the various private schools. Bell established his own private school of anatomy and surgery in London and subsequently purchased the famous William Hunter School in Great Windmill Street. The fortunes of the school declined after he sold the school in 1826 and joined the faculty of the new University of London. Meanwhile, he was kept busy with the publication of his System of Operative Surgery, which in its second (1814) edition included his Dissertation on Gun-shot Wounds, and the preparation of his famous The Anatomy of Expression in Painting.
Anatomy of the Expression of Emotions
Authors: Aminoff Michael J.
Published: November 2017

A discussion of medical artists, wax modeling, and medical museums in the eighteenth and nineteenth centuries is followed by an account of Charles Bell’s enormously successful book, Essays on the Anatomy of Expression in Painting. The foundation of the Royal Academy of Art is described; Bell’s applied unsuccessfully to be professor of anatomy there. His book reflected his creationist viewpoint and his belief in intelligent design, but nevertheless it founded the scientific study of expression. It stimulated Charles Darwin to write on the same topic many years later from an evolutionist viewpoint. In recent years, a resurgence of interest has occurred in the topic by psychologists and law officers as a means of detecting deception. Bell’s book also had a major impact on the artistic representation of expression and inspired a number of contemporary painters, especially the Pre-Raphaelites.
Swings and Roundabouts
Authors: Aminoff Michael J.
Published: November 2017

Both Charles Bell and his brother George married into the Shaw family of Ayrshire. Bell’s character, personality, and social life are explored, particularly as they change throughout the years. In 1814, he was elected surgeon to the Middlesex Hospital in London. He worked hard as a general surgeon and teacher with an interest in the genitourinary system, and described a muscle in the urinary bladder since named after him. The death of his brothers Robert (1816) and John (1820) did not interrupt his work. The publication of his famous Illustrations of the Great Operations of Surgery in 1821 was followed by a shift of the focus of his work to the nervous system, aided by John and then Alexander Shaw. A dispute with the famous surgeon SirAstley Cooper concerning the role of surgery after spinal trauma led to angry words between them, but they remained friends.
In and Out of the Central Nervous System
Authors: Aminoff Michael J.
Published: November 2017

In 1811, Bell had printed privately a monograph titled Idea of a New Anatomy of the Brain. In it, Bell correctly showed that the anterior but not the posterior roots had motor functions. François Magendie subsequently showed that the anterior roots were motor, and the posterior roots were sensory. This led to a dispute about priority during which Bell republished some of his early work with textual alterations to support his claims. Bell was involved in a similar dispute with Herbert Mayo concerning the separate functions of the fifth (sensory) and seventh (motor) cranial nerves, and Mayo today is a forgotten man. In both instances, Bell deserves credit for the concepts and initial experimental approach, and Magendie and Mayo deserve credit for obtaining and correctly interpreting the definitive experimental findings.
New Classrooms: Old Struggles
Authors: Aminoff Michael J.
Published: November 2017

Charles Bell was an internationally renowned teacher of anatomy and surgery and an eloquent advocate of natural theology. His writings on the anatomy of expression had a major influence on art and on the training of painters and artists, and they gave birth to physiological psychology. Bell founded his own anatomy school, took over the well-known Hunterian school in Great Windmill Street, was a clinical teacher at one of the great London hospitals, was the most famous professor appointed to the medical department when the University of London was established, helped to found the Middlesex Hospital Medical School, and, finally, held a prestigious chair of surgery at the University of Edinburgh. His association with the University of London was brief, however, because his role was unclear, the institution was mismanaged, and the environment was acrimonious.
Endovascular
Authors: Daou Badih , Jabbour Pascal
Published: November 2017

Endovascular neurosurgery has evolved dramatically since the first description of aneurysm coiling in 1991 and is now employed as a primary treatment strategy for managing a multitude of cerebrovascular pathologies, including aneurysms, arteriovenous malformations (AVMs), and acute ischemic stroke. The endovascular approach offers an attractive, minimally invasive alternative for aneurysm treatment with low procedure-related morbidity and mortality. The durability and long-term efficacy of endovascular interventions is continuously evolving, especially with the introduction of newer coils, stents, and flow-diversion techniques. Endovascular management of AVMs can be used for presurgical embolization, preradiosurgical intervention, or palliative embolization or as a primary treatment for curative embolization, depending on the characteristics of the lesion. Advances in endovascular management of acute stroke have further increased the therapeutic window of recombinant tissue plasminogen activator administration using the intraarterial route and have led to the introduction of new devices for clot removal and vessel recanalization.
Academic Medicine
Authors: Hellman Samuel
Published: November 2017

The proper education of a doctor must not be restricted to the sciences but rather must include study of the humanities and the social sciences. This is best achieved by having an interactive and physically integrally located medical school. Not only must medicine be based on modern biology, a biology education is also essential for all college undergraduates. One cannot consider genetic engineering if one does not understand what a gene is and how it is controlled. Unique to medical education are the places of medical practice. Besides providing a site of learning, the teaching hospital must provide excellent patient care and be responsive to the surrounding community. The university must embrace these other goals. Society should provide high quality health care for all. This cannot be achieved if only the lowest cost is the goal. While resources are limited, economic efficiency cannot be the only parameter.
It’s Personal
Authors: Webster Lynn R.
Published: November 2017

“It’s Personal” makes the point that pain is a bio-psycho-social-spiritual experience. And because it is a broad-based experience, it requires a broad-based approach to bring healing. People in pain need to be both treated by a diversity of medical professionals and supported by the important people in their lives. By showing understanding and compassion, anyone who knows and cares about someone in pain can minister an inner sense of healing. Those who are in pain need others to listen to their stories and accompany them in their journey toward recovery. Chapter key idea: More than just a medical condition, chronic pain affects everything in a person’s life.
Management of stable CF lung disease
Authors: Simmonds Nicholas , Dhouieb Elaine
Published: November 2017

This chapter addresses the nuts and bolts of everyday management of CF lung disease. It outlines the most up-to-date recommendations to ensure lung function is optimised and remains as stable as possible, including all the latest specialist CF drugs and advancements in respiratory physiotherapy techniques. Topics covered include clinical and radiological assessments of lung disease; airway clearance techniques; inhaler device selection; inhaled therapies (including the new antibiotics and drugs targeting mucus production and clearance); oral antibiotics, including azithromycin; fungal treatment; and the new era of mutation-specific drug therapy. There is also important advice on the current recommendations for exercising and travelling with CF. Overall, this chapter provides a comprehensive overview to the busy clinician requiring the latest information on the day-to-day management of CF lung disease.
Management of respiratory exacerbations
Authors: Gilchrist Francis J , Horsley Alex
Published: November 2017

Cystic fibrosis lung disease is characterized by chronic infection, inflammation and a progressive loss of lung function. Patients are also affected by recurrent episodes of increased respiratory symptoms, called exacerbations which have a detrimental effect on quality of life, the rate of lung function decline, and mortality. Early diagnosis and treatment is vital. Diagnosis relies on a combination of symptoms, examination findings, the results of laboratory tests, and lung function. Antibiotics are the mainstay of treatment but airway clearance, nutrition, and glucose homeostasis must also be optimized. Mild exacerbations are usually treated with oral antibiotics and more severe exacerbations with intravenous antibiotics. The choice of antibiotic is guided by the patient’s chronic pulmonary infections, the in-vitro antibiotic sensitivities, known antibiotic allergies, and the previous response to treatment. In patients with chronic Pseudomonas aeruginosa infection, antibiotic monotherapy is thought to increase the risk of resistance and treatment with 2 antibiotics is therefore suggested (usually a β‎-lactam and an aminoglycoside). Although there is a lack of evidence on the duration of treatment, most patients receive around 14 days. This can be altered according to the time taken for symptoms and lung function to return to pre-exacerbation levels. If patients are carefully selected and receive appropriate monitoring, home intravenous antibiotics can be as effective as in-patient treatment. They are also associated with decreased disruption to patients / family life, decreased risk of cross infection and decreased costs.
Gastrointestinal disease and nutrition
Authors: Taylor Christopher , Connolly Sally
Published: November 2017

This chapter discusses the common gastrointestinal and nutritional consequences of cystic fibrosis (CF) including hepato-biliary disease. The pathophysiology of obstructive gut disease (meconium ileus and distal ileal obstruction) is discussed with reference to CFTR dysfunction. The diagnosis and management of gastro-oesophageal reflux, an increasingly common problem in both children and adults with CF, is also considered in some depth. A new section on eosinophilic gut disease has been added. The importance of nutrition in maintaining lung function is emphasized with a section on pancreatic enzyme physiology and guidance on optimizing pancreatic enzyme replacement therapy. An investigation plan to exclude concomitant gut disease for a child with poor weight gain is given, together with a section on invasive nutritional support. The diagnosis of hepatic disease and biliary complications is considered together with suggested treatments and a long-term monitoring plan
Cystic fibrosis-related diabetes
Authors: O’Riordan Stephen MP , Moran Antoinette
Published: November 2017

This chapter on CFRD reviews the ever-evolving topic and provides up-to-date information on how to diagnose and manage cystic fibrosis-related diabetes CFRD in the acute and chronic setting. The treatments necessary to treat and prolong life in CF, including their unique dietary requirements, must always be followed as a first priority, with diabetes care adjusted accordingly. Early intervention with insulin has been shown to reverse clinical deterioration, even in those with mild diabetes. Newly emerging treatments for CF which have the potential to restore defective chloride channels may have implications for the development and treatment of CFRD.
Whilst CFRD shares features of both type 1 and type 2 diabetes, there are important differences which necessitate a unique approach to diagnosis and management. Factors specific to CF that variably affect glucose metabolism include chronic respiratory infection and inflammation, increased energy expenditure, malnutrition, glucagon deficiency, and gastrointestinal abnormalities.
Metabolic and musculoskeletal effects of cystic fibrosis
Authors: Hill Uta , Ashbrook Jane , Haworth Charles
Published: November 2017

This chapter provides a comprehensive update on the prevention, recognition, and treatment of low bone mineral density in people with CF. As life expectancy improves, the extra-pulmonary complications of CF are becoming increasingly important to quality of life. Up to 25 per cent of CF patients have reduced bone mineral density in adulthood, leading to the development of fragility fractures which cause pain, thereby interfering with airway clearance and predisposing to pulmonary infection. Osteoporosis can be a relative contraindication for lung transplantation.
Other important musculoskeletal issues including CF arthropathy, growth, and urinary incontinence are covered. CF arthropathy is a non-erosive episodic sero-negative arthritis, often difficult to treat and which may require specialist input. Urinary incontinence is common girls and women with CF and has a negative impact on quality of life and ability to complete therapies. The pathophysiology and management of urinary incontinence are discussed.
Pharmacy and the CF pharmacopoeia
Authors: Cox Katrina
Published: November 2017

Medicines are an integral part of CF care and are prescribed and administered with the intention of improving health and quality of life. Many factors are taken into account when choosing a medicine to prescribe for a patient. Once prescribed, medicines require monitoring for effectiveness and side effects, the CF specialist pharmacist is well placed to do this. The CF Pharmacopoeia details important characteristics of these medicines. Allergies to medicines can pose a challenge, but desensitising individuals with allergies to antibiotics offers an opportunity to use choices that would otherwise be contraindicated.
Introduction to Part 1: Overview
Authors: Omaswa Francis , Crisp Nigel
Published: November 2017

Chapter 1 provides an overview of the structure and contents of this resource. It begins by explaining why it was written and goes on to describe the context and particular challenges facing African health leaders. It explains its six-part structure, which brings out the key themes and describes the leaders from three different generations who have contributed to it.
Epidemiology and health policy in Africa
Authors: Sambo Luis
Published: November 2017

Chapter 6 describes the epidemiological challenges facing Africa, the way in which the wider determinants of health affect the population, and the wider international context within which health systems developed in recent years. It covers how Africa is facing a disproportionately large share of the world’s burden of disease with a tiny part of its resources, and also how Africans, supported by international partners, have tackled these problems with considerable success. It also discusses how some of the intractable public health challenges and underlying systems’ issues remain serious challenges to be tackled in coming years. It concludes with thoughts on how health in Africa has changed in the last 10 years and the need for a more holistic health systems approach in the future.
The development of community directed treatment for tackling river blindness
Authors: Amazigo Uche
Published: November 2017

Chapter 9 tells the story of how African researchers developed a way of engaging rural communities themselves in delivering and monitoring the treatment—with spectacular results. The author describes the difficulties faced in bringing together all the participants, aligning organizational and national interests, working in post-conflict situations, and developing the network of villages and community distributors. It shows how she and her colleagues succeeded through a rigorous and energetic approach, and through supporting the local people.
The evolution of professional education and health systems in sub-Saharan Africa
Authors: Monekosso Gottlieb
Published: November 2017

Chapter 14 charts the development of professional education in sub-Saharan Africa from the pre-colonial period, into the colonial and through to the twenty-first century. It shows how pioneering leaders have worked creatively to overcome the shortages of people and resources, and provided trained people to meet the most pressing needs in their countries. It invokes the need for cooperation with a wide range of international partners but also discusses that, while in providing opportunities for education, it has also provided opportunities for emigration. It covers the importance of intellectual rigour married to a thorough understanding of local circumstances, and that policies represent the needs and wants of local populations.
Introduction to Part 5: Health for the whole population—leaving no-one behind
Authors: Omaswa Francis , Crisp Nigel
Published: November 2017

Chapter 16 addresses the way in which universal health coverage has become one of the most important concepts in global health. It sets the scene for the following chapters in which leaders discuss the implementation of universal health coverage in Rwanda, South Africa, and Ghana.
The future: view from a Minister
Authors: Kargbo Miatta
Published: November 2017

Chapter 22 covers the views of the Honourable Miatta Kargbo MBA, one of the newest and youngest health ministers in Africa, about the future of health and healthcare in Africa, as well as for her own country. In this chapter she sets out an optimistic vision whilst at the same time describing very clearly the many challenges that will have to be met. She also describes the practical steps that can and are being taken to improve health and ensure access to healthcare, even for the poorest.
From a dream to a nightmare
Authors: McCann Shaun R.
Published: November 2017

Historically, one of the contentious issues in the understanding of blood was the clotting process. Ancient observers posited that a cooling process led to clotting, while William Harvey, writing in the seventeenth century, postulated that fibrous mucous in the blood contributed to clotting. It was through the study of haemophilia patients in the eighteenth and nineteenth centuries that the underlying factors in the clotting mechanism were first understood, and not until the 1930s that the clotting factor involved, Factor VIII, was identified. Subsequent attempts to treat patients with Factor VIII concentrates led to an understanding of the transmission process of hepatitis B. The link between haemophilia and hepatitis B was subsequently central to the early understanding of the AIDS virus.
Red blood cells
Authors: McCann Shaun R.
Published: November 2017

Red blood cells, erythrocytes, are unique in that they do not contain a nucleus. This fact facilitates the study of their metabolism. Erythrocytes contain the protein pigment haemoglobin, which is in solution in the cells and consists of globin chains and iron. In this chapter, the development of the understanding of erythrocytes is linked to the blood conditions haemolytic anaemia and paroxysmal nocturnal haemoglobinuria. Premature destruction of erythrocytes, in the absence of blood loss, is termed haemolysis. If the bone marrow is unable to compensate adequately, then anaemia ensues and the condition is called haemolytic anaemia. The underlying defect is a deficiency in the activity of the enzyme glucose-6-phosphate dehydrogenase, termed G6PD deficiency.
Blood and the hidden virus
Authors: McCann Shaun R.
Published: November 2017

A major achievement in the history of blood transfusion was discovery of the rhesus blood groups. The work of Philip Levine and Rufus Stetson led to the discovery of the Rh factor and its relevance to haemolytic disease of the newborn. Later developments led to the generation of the anti-Rh (anti-D) antibodies. The chapter goes on to discuss the contamination of anti-D blood products with hepatitis C and the subsequent isolation of the hepatitis C virus. The contamination of donated blood products by hepatitis C and variant Creutzfeldt–Jakob disease is discussed, with specific relevance to the practice of blood donation and screening processes.
The role of technology in haematology
Authors: McCann Shaun R.
Published: November 2017

Various technologies have changed and improved the practice of haematology. Because it is possible to obtain blood cells so readily (via a simple venepuncture), haematology has been at the forefront of technological developments in medicine. The diagnosis of both malignant and benign haematological disorders has become more exact because of the technological advances outlined, and the understanding of the pathogenesis of many diseases has been advanced as a direct result of the application of technologies such as immunofluorescence, confocal and electron microscopy, automated cell counting, flow cytometry, digital cell morphology, advanced staining techniques, and PCR. However, it is important to stress that all technologies and ‘tests’ need to be cautiously interpreted, and a full history and physical examination should always be the first step in the investigation of patients.
Vitamin A in pregnancy and breastfeeding
Authors: Gluckman Sir Peter , Hanson Mark , Seng Chong Yap , Bardsley Anne
Published: November 2017

Vitamin A is critical for visual and reproductive function, supports resistance to infection, and is required for the development of multiple organ systems. including the heart, lungs, kidneys, and skeleton. Both excess and deficiency of vitamin A in pregnancy are associated with birth defects. High intakes of vitamin A, either in the form of supplements or in concentrated food sources such as liver, should be avoided in pregnancy, particularly between day 15 and day 60 post conception. However, in areas with endemic vitamin A deficiency, supplementation in late pregnancy is recommended to prevent night blindness. Most women who are at low nutritional risk can meet their early pregnancy vitamin A requirement from food sources, but should increase their vitamin A intake from food during the third trimester and through lactation.
Vitamin B2 (riboflavin) in pregnancy and breastfeeding
Authors: Gluckman Sir Peter , Hanson Mark , Seng Chong Yap , Bardsley Anne
Published: November 2017

Riboflavin is a cofactor for enzymes involved in energy generation, biosynthesis, detoxification, and electron-scavenging pathways, as well as in the metabolism of other B vitamins. Deficiency is rare in developed countries; it is encountered almost invariably in combination with deficit of other B vitamins in areas of poor overall nutrition. Deficiency is endemic in populations whose staple diet consists of rice and wheat, with low or no consumption of meat and dairy products. Infants of riboflavin-deficient mothers tend to be deficient themselves at birth and remain deficient through breastfeeding and weaning. To ensure adequate riboflavin supply in both mother and infant, an increase in dairy products and/or meat consumption, particularly during lactation, may be necessary in some women.
Vitamin B12 (cobalamin) in pregnancy and breastfeeding
Authors: Gluckman Sir Peter , Hanson Mark , Seng Chong Yap , Bardsley Anne
Published: November 2017

Vitamin B12 is required for the synthesis of fatty acids and myelin and so is crucial for normal neurological function and maintenance of the CNS. In conjunction with folate, it is involved in red blood cell formation and DNA synthesis, and in embryogenesis, it is important for proper neural tube formation and brain development. Maternal intake during pregnancy is important, as only newly absorbed vitamin B12, and not that stored in the maternal liver, is concentrated in the placenta. Despite the active transfer during pregnancy, the vitamin B12 content in the newborn is low, and the infant is dependent on breast milk for ongoing needs. Pregnant and lactating women should ensure that their diet contains sufficient (animal) sources of vitamin B12; those consuming vegan or strict vegetarian diets should either take vitamin B12 supplements or seek foods that have been fortified with vitamin B12.
Vitamin K in pregnancy and breastfeeding
Authors: Gluckman Sir Peter , Hanson Mark , Seng Chong Yap , Bardsley Anne
Published: November 2017

Vitamin K is involved in blood clotting, and lack of this nutrient results in a hypocoagulable state, associated with a high risk of bleeding events. Deficiency is rare among adults, because vitamin K is widely available in foods. However, the placenta transmits vitamin K relatively poorly, leading to a general deficiency in full-term neonates, who are also particularly vulnerable to the effects of low vitamin K levels because of their immature clotting systems. Deficiency can lead to intracranial haemorrhage following birth trauma, or classic vitamin K deficiency bleeding. It is important to maintain adequate vitamin K status throughout pregnancy in order to avoid added risk to the neonate at birth and in the first few weeks of life. Supplementation of newborns by intramuscular injection should be universal.
Calcium in pregnancy and breastfeeding
Authors: Gluckman Sir Peter , Hanson Mark , Seng Chong Yap , Bardsley Anne
Published: November 2017

Most calcium in the body is present in the skeleton, where it serves a structural role and also as a reservoir for use in other tissues. During pregnancy, calcium is accumulated in the fetal skeleton, mostly during the third trimester when bone growth is at its peak. Although this increases the demand on maternal bone stores, the calcium transfer to the fetus is balanced by increased intestinal calcium absorption in the mother, mediated by compensatory changes in vitamin D synthesis and endogenous hormone levels. Bone loss is minimized if calcium intake is maintained at 1,000#amp;#x2013;1,200 mg/day during pregnancy. This intake level builds up calcium stores in early pregnancy for increased fetal transfer in the third trimester. Additional dietary calcium is usually not required if pre-pregnancy intake is adequate, although pregnant adolescents and women carrying multiple fetuses may require supplementation.
Zinc in pregnancy and breastfeeding
Authors: Gluckman Sir Peter , Hanson Mark , Seng Chong Yap , Bardsley Anne
Published: November 2017

Zinc is an essential mineral involved in gene expression, cell growth and division, neurotransmission, and reproductive and immune functions. It is crucial for periods of growth, including pregnancy and lactation, infancy, childhood, and adolescence. Daily requirements in pregnancy increase by ~40, so adequate zinc stores should be ensured prior to pregnancy so that the high requirements of the developing fetus can be met. Inadequate zinc intake often accompanies general protein/calorie malnourishment but is also seen in individuals consuming poor quality diets. Diets low in animal protein and/or high in phytates (e.g. in whole grains) provide limited amounts of bioavailable zinc. Prenatal vitamins containing zinc are advisable with such diets. Zinc is required for male fertility, and supplementation may improve fertility in subfertile men.
Manganese in pregnancy and breastfeeding
Authors: Gluckman Sir Peter , Hanson Mark , Seng Chong Yap , Bardsley Anne
Published: November 2017

Manganese is both an essential element and a potent neurotoxin. It is involved in cellular metabolic processes and is a component of antioxidant enzymes. Uptake and efflux of manganese is tightly regulated, as both deficiency and excess can result in disease states. Manganese has essential functions in maternal health and fetal development, and in healthy women adequate amounts can be obtained from a mixed diet of grains, cereals, and fruits. Supplements containing manganese should be used with caution, as excess intake can have neurotoxic effects on the developing brain. Maternal intake in pregnancy and lactation is not likely to be a worry in most cases, as transfer of manganese to the fetus and into breast milk is limited.
Pre-conception maternal body composition and gestational weight gain
Authors: Gluckman Sir Peter , Hanson Mark , Seng Chong Yap , Bardsley Anne
Published: November 2017

Maternal diet and body composition prior to pregnancy influence gestational weight gain and infant growth patterns. Low maternal pre-pregnancy weight, low BMI, and low attained weight throughout pregnancy are associated with impaired fetal growth, while obesity and high weight gain increases the risks of multiple adverse pregnancy outcomes and excessive fetal growth and offspring obesity. Currently the US Institute of Medicine guidelines for gestational weight gain are the only ones available for developed countries where mean maternal height is similar to that in the US. While these guidelines should be followed, attention should be given to body composition before pregnancy, and measures of body habitus such as maternal height should be taken into account.
Guidelines for pregnancy
Authors: Gluckman Sir Peter , Hanson Mark , Seng Chong Yap , Bardsley Anne
Published: November 2017

If a pregnant woman has not had pre-conception counselling, it is important to ensure as soon as possible in early pregnancy that she understands her nutrient requirements, and what comprises a balanced diet and healthy body composition. The advice should include weight gain goals in pregnancy, a list of unsafe foods, healthy exercise behaviours, and the effects of alcohol and drugs. Energy intake needs in early pregnancy do not increase from pre-pregnancy levels; women should focus on eating well for pregnancy, and not eating more. Specific attention should be paid to intakes of folate, vitamin A, vitamin B12, vitamin D, iron, and iodine. Glucose status should be monitored in mid-pregnancy. Energy requirements increase in mid- to late pregnancy, but attention should also be paid to the macronutrient balance. If the diet is low in oily fish as a source of polyunsaturated fatty acids, supplementation should be considered.
What is Epilepsy?
Authors: Schmidt Dieter , Shorvon Simon
Published: November 2017

The definition of disease is not straightforward. Whilst an epileptic seizure—a symptom—can be considered as an electrochemical cerebral phenomenon, defining epilepsy is more difficult. It is more than just a strictly medical and mechanical brain disorder, but has signification that extends beyond the individual, and has societal and cultural connotation. Disease is sometimes considered to be defined by causation, but deciding what is cause in epilepsy is also a complicated question. The distinction between disability and disease can also be blurred. If definition is difficult, so inevitably is classification. John Hughlings Jackson made the famous distinction between the classification of a gardener and a botanist and the lessons he drew still apply today. The sometimes baffling controversies in this area are dissected, within the context of their historical evolution since the time of Jackson.
Modern Blockbusters
Authors: Schmidt Dieter , Shorvon Simon
Published: November 2017

Five modern antiepileptic drugs have reached the fabled blockbuster status (more than $1 billion sales per year), albeit for treatment of not only epilepsy but for other disorders of the central nervous system too. These drugs generated huge profits, and the chapter asks, how were they discovered and are they worth their money? The history of the five blockbusters—levetiracetam, lamotrigine, topiramate, gabapentin, and pregabalin—provides an interesting study of chance, science, wrong ideas, and finance, and most importantly luck. The discovery of the antiepileptic effects of some of these compounds was stumbled upon by simple good fortune, and others barely escaped an early demise during an unpromising early development. Despite the commercial success, no study has shown any of these drugs to be any more effective than older drugs, yet they made billions. This chapter examines how industry could do this and what the drivers are for success.
Culs-de-Sac and Bureaucracies
Authors: Schmidt Dieter , Shorvon Simon
Published: November 2017

This chapter examines some of the curate’s eggs of epilepsy. Examples in which the bright light of success is obscured by shadows cast from the dark side. It starts by pointing out the erratic nature in which science has advanced in the modern period, using the theories of causation of epilepsy as an example. This is not a linear path to the stars but a course influenced by societal and political fashion, with many culs-de-sac and wrong turnings, now as much as in the past. It considers, too, the extraordinary bureaucracies which underpin communication in epilepsy today—the journals, the congresses, and the professional organisations—and that govern the regulation of drug therapy. The landscapes within which these bureaucracies operate are often marked by short-termism, politics of the parish pump variety, the impact of often rather tiresome personalities, and the dead hand of regulation and ‘guidance’. There have been steps forward and some reverses, but most is Brownian movement.
Introduction to the measurement and valuation of health
Authors: Brazier John , Ratcliffe Julie , Salomon Joshua A. , Tsuchiya Aki
Published: November 2017

This chapter provides the rationale for measuring and valuing health benefits for economic evaluation. It covers the limitation of using conventional patient-reported outcome measures of health (e.g. SF-36) in economic evaluation. It then introduces the quality-adjusted life year (QALY), which attempts to value the benefits of health care in terms of a measure that combines the impact on survival and quality of life using the numeraire of a year in full health. This chapter introduces the core building blocks of measuring and valuing health: describing health; techniques for valuing health; deciding who should value health; and taking account of social consideration in the aggregation of QALYs.
Using ordinal response data to estimate cardinal values for health states
Authors: Brazier John , Ratcliffe Julie , Salomon Joshua A. , Tsuchiya Aki
Published: November 2017

There exists a strong methodological foundation for estimating cardinal values from ordinal information, originating in psychology but commonly applied in areas as diverse as consumer marketing, political science, transportation research, and environmental economics. Over recent years there has been a steady rise in the use of these approaches to estimate health state values. Potential advantages claimed for ordinal data collection approaches include relative ease of comprehension and administration, and greater reliability corresponding to reduced measurement error. Another advantage of some types of ordinal data collection methods is that the preferences or judgements they elicit are not contaminated by risk aversion (as in the standard gamble), or by time preference (as in the time trade-off).
Conclusions: measurement and valuation of health
Authors: Brazier John , Ratcliffe Julie , Salomon Joshua A. , Tsuchiya Aki
Published: November 2017

This book addresses the main questions surrounding the measurement and valuation of health. It shows that there are many different answers to to questions regarding how to describe health, valuation methods, whose values, what instruments to use, how to aggregate QALYs, and how to use the health state utility values in economic evaluation. This chapter examines the implications of this diversity for policy making, the use of a reference case, and briefly reviews the guidelines used by major policy makers (e.g. NICE) around the world. We cannot predict how the field is likely to develop over the next decade, but we are sure it will lose none of its intellectual challenge and controversy.
Pluralism, incommensurability, and scientific change
Authors: Longino Helen E.
Published: November 2017

Chapter 2 covers views on the nature of scientific change (continuous or discontinuous; cumulative or revolutionary) and about the role of external considerations in science (corruptive or necessary), and how they depend on prior views about the nature of scientific knowledge. It sketches the principal epistemological ideas of logical empiricism, holism, and contextualism and outlines the attitudes toward change and external influence each licenses. The licensed attitudes are illustrated by reference to contemporary research on human aggression.
History and epistemology of psychopathology
Authors: Berrios German E.
Published: November 2017

Chapter 5 addresses how, whether as a general concept or as a feature of psychiatry, ‘change’ remains difficult to define because its meaning is parasitical upon metaphysical categories such as object, event, property, and time. It might be more practical to explore it in relation to specific ontological regions (e.g., physics, biology, and sociology). The biological and social sciences (both relevant to psychiatry) countenance change. The targets of change in psychiatry remain its epistemological structure and its objects. Change can be explored transepistemically by comparing historical narratives of madness or intraepistemically, by detecting variations within a given narrative (e.g., religious, social, or neurobiological). These studies can be value-neutral or value-laden (the latter can be redefined ‘change’ as ‘progress’). ‘Change’ can be accounted for by the Cambridge model of symptom formation. According to this, mental symptoms are events resulting from configuratory action undertaken by sufferers to make sense of (often) distressing information invading their awareness. This information can be biological signals (released by a distressed brain networks) or symbols (resulting from social interaction or personal reflection). Configurators (personal, sociocultural, dialogical, etc.) shape this inchoate information into effable experiences. Due to biological mutation or social change affecting the configurators, mental symptoms are liable to change in time. Hence, the objects of psychiatry are not eternal and will be replaced in the future.
Can hybridity overcome dualism?
Authors: Longino Helen E.
Published: November 2017

Chapter 6 is a commentary on Chapter 5, which discusses the history and epistemology of psychopathology, and covers the definition of change as a feature or a general concept of psychiatry, and the definition’s relation to specific ontological regions (e.g., physics, biology, and sociology).
Introduction to “Varieties of social constructionism and the problem of progress in psychiatry”
Authors: Kendler Kenneth S.
Published: November 2017

Chapter 10 is an introdcution to Chapter 11, which covers the ideas surrounding the varieties of social constructionism and the problem of progress in psychiatry. It specifically addresses issues surrounding schizophrenia, differences of opinion about psychiatric disorders, and the term ‘inclusionary social constructionism’.