bluuebunny/crossref_metadata_2025 huggingface dataset:
Analyzing a parametric change in Brazilian Portuguese
Authors: Duarte Maria Eugenia Lammoglia
Published: April 2017

This chapter presents an empirical investigation of a process of change in course in Brazilian Portuguese related to the re-setting of the value of the Null Subject Parameter. Structural constraints that facilitate or refrain the change towards overt pronominal subjects come from diachronic and synchronic analyses. A discussion concerning how non-referential subjects are affected is also presented. Brazilian Portuguese topic prominence will be shown to be responsible not only for the lack of lexical expletives in the system but also for the emergence of a number of strategies consisting in the raising of referential contituents to Spec, TP, so as to avoid a null expletive. The theoretical framework guiding the analysis associates Principles and Parameters Theory (Chomsky, 1981 and subsequent work) and the model to study Language Variation and Change as proposed by Weinreich, Labov, and Herzog (1986). It will be shown that the theoretical support adopted highlights the path for the empirical analysis, from the establishment of hypotheses and linguistic factors constraing the process to the interpretation of the effects of the change.
Agreement in Portuguese
Authors: Vieira Sílvia Rodrigues , Brandão Sílvia Figueiredo
Published: April 2017

The purpose of this chapter is to relate the status of linguistic rules (Labov, 2003) and the characterization of varieties/languages. Based on the assumptions of Variationist Sociolinguistics, patterns of nominal and verbal number agreement in European and Brazilian Portuguese are described. In order to bring evidence to support the analysis, we present quantitative and qualitative characterization of data. Results from recent investigations (Mota & Vieira, 2013) allow us to outline clear differences between Brazilian and European patterns. Defining the typology of rules – variable, semi-categorical, categorical – can serve to evaluate typological profiles for several grammatical phenomena and it is a strong methodological procedure to distinguish what is apparently variable and what actually constitutes a general trend or default option.
Dative variation in the Portuguese of São Tomé
Authors: Gonçalves Rita
Published: April 2017

Portuguese of São Tomé (pst) exhibits two strategies to express Recipients: double object constructions (DOC) and ditransitive prepositional constructions (DPC), which employ either the preposition a ‘to’ or the preposition para ‘toward’ (R. Gonçalves 2010). Using data from a spoken corpus, we will analyze to which extent linguistic and extra-linguistic variables can play a role in pst dative variation. Therefore, we will discuss whether it follows Rappaport-Hovav and Levin’s (2008) distinction between give-type verbs (core dative verbs), which occur in both DOC and DPC introduced by a functional preposition, and throw/send-type verbs (non-core dative verbs), which can occur in a DPC introduced either by a functional or directional preposition. We will further address the role of contact with Santome.
Simple past with pluperfect interpretation
Authors: Martins Kellen Cozine , de Paiva Maria da Conceição
Published: April 2017

In this chapter, we analyze the variation between simple past and compound pluperfect forms to indicate past-in-the-past in European and Brazilian spoken Portuguese. Comparing data from Rio de Janeiro and Lisbon, we focus on the effect of three variables: verbal person, reference time and type of clause. Using multivariate analysis, we discuss the traditional assumption according to which the simple past with past-in-the-past reference is constrained in the third-person plural. We provide strong evidence that semantic and discursive relations are of utmost importance to the interpretation of simple past as past-in-the-past.
Fabrication and drag reduction of superhydrophobic surface on steel substrates
Authors: Zhang Haifeng , Tuo Yanjing , Wang Qingchun , Jin Bingjie , Yin Liang , Liu Xiaowei
Published: April 2017

Superhydrophobic surfaces have attracted significant attention because of their potential applications in various industrial fields. In this study, a chemical process for fabricating ZnO nanowires on steel substrates is developed by using a chemical etching and hydrothermal synthesis method. The resultant surface exhibits binary micro/nanostructures. The modified sample exhibits a water contact angle of 164.9° and a sliding angle of 2.3° for a 5-μL water droplet. An experimental setup is created to measure the drag friction on the surface of the sample. Experimental results show that the drag reduction radio for the as-prepared sample is 40–50%.
Spawning, Embryology, and Larval Development of the Milletseed Butterflyfish Chaetodon miliaris in the Laboratory
Authors: Degidio Jon-Michael L A , Yanong Roy P E , Watson Craig A , Ohs Cortney L , Cassiano Eric J , Barden Kevin
Published: April 2017

As part of the Rising Tide Conservation effort to advance marine ornamental aquaculture the Milletseed Butterflyfish Chaetodon miliaris (also known as Millet Butterflyfish) was chosen as a candidate species for developing butterflyfish aquaculture methodologies. Thirty-five mature Milletseed Butterflyfish were imported to University of Florida's Tropical Aquaculture Laboratory in Ruskin, Florida, from The Rainbow Reef exhibit at Aulani, a Disney Resort and Spa in Ko Olina, Hawaii, for evaluation. Spawning behavior was documented through personal and video observation five times. Eggs were collected immediately after spawning and checked for fertilization, and a sample of 100 ± 10 eggs were photographed every hour until hatching to document embryological development. Larval development was monitored through multiple rearing trials. Larvae were stocked into 128-L, cylindrical, rearing tanks at 15–20 larvae/L and fed nauplii of the copepod, Parvocalanus crassirostris, and the microalgae, Tisochrysis lutea, was added to green the water. Samples of larvae were measured using notochord length from the tip of the snout to the edge of the notochord prior to flexion, SL from the tip of the snout to the edge of the hypural plate, and TL. Spawning occurred in broodstock tanks between one dominant male and a single female with a large, swollen abdomen. Eggs of the Milletseed Butterflyfish were small, spherical, pelagic, and transparent and hatched after a 28-h period at 25.5°C. Newly hatched larvae had unpigmented eyes and a closed digestive tract and measured 1.20–1.24 mm in notochord length. Larvae were capable of feeding at 4 d posthatch (dph), fully absorbed the yolk sac by 7 dph, and began forming the tholichthys plates at 24 dph. Larvae survived to 44 dph in preliminary culture trials and measured 6.49–6.56 mm TL. Further investigation into the culture requirements of Milletseed Butterflyfish will supply a crucial base for developing aquaculture protocols for other marine ornamental species.
MAARS: a novel high-content acquisition software for the analysis of mitotic defects in fission yeast
Authors: Li Tong , Mary Hadrien , Grosjean Marie , Fouchard Jonathan , Cabello Simon , Reyes Céline , Tournier Sylvie , Gachet Yannick
Published: April 2017

Faithful segregation of chromosomes during cell division relies on multiple processes such as chromosome attachment and correct spindle positioning. Yet mitotic progression is defined by multiple parameters, which need to be quantitatively evaluated. To study the spatiotemporal control of mitotic progression, we developed a high-content analysis (HCA) approach that combines automated fluorescence microscopy with real-time quantitative image analysis and allows the unbiased acquisition of multiparametric data at the single-cell level for hundreds of cells simultaneously. The Mitotic Analysis and Recording System (MAARS) provides automatic and quantitative single-cell analysis of mitotic progression on an open-source platform. It can be used to analyze specific characteristics such as cell shape, cell size, metaphase/anaphase delays, and mitotic abnormalities including spindle mispositioning, spindle elongation defects, and chromosome segregation defects. Using this HCA approach, we were able to visualize rare and unexpected events of error correction during anaphase in wild-type or mutant cells. Our study illustrates that such an expert system of mitotic progression is able to highlight the complexity of the mechanisms required to prevent chromosome loss during cell division.
A novel Munc13-4/S100A10/annexin A2 complex promotes Weibel–Palade body exocytosis in endothelial cells
Authors: Chehab Tarek , Santos Nina Criado , Holthenrich Anna , Koerdt Sophia N. , Disse Jennifer , Schuberth Christian , Nazmi Ali Reza , Neeft Maaike , Koch Henriette , Man Kwun Nok M. , Wojcik Sonja M. , Martin Thomas F. J. , van der Sluijs Peter , Brose Nils , Gerke Volker
Published: April 2017

Endothelial cells respond to blood vessel injury by the acute release of the procoagulant von Willebrand factor, which is stored in unique secretory granules called Weibel–Palade bodies (WPBs). Stimulated WPB exocytosis critically depends on their proper recruitment to the plasma membrane, but factors involved in WPB–plasma membrane tethering are not known. Here we identify Munc13-4, a protein mutated in familial hemophagocytic lymphohistiocytosis 3, as a WPB-tethering factor. Munc13-4 promotes histamine-evoked WPB exocytosis and is present on WPBs, and secretagogue stimulation triggers an increased recruitment of Munc13-4 to WPBs and a clustering of Munc13-4 at sites of WPB–plasma membrane contact. We also identify the S100A10 subunit of the annexin A2 (AnxA2)-S100A10 protein complex as a novel Munc13-4 interactor and show that AnxA2-S100A10 participates in recruiting Munc13-4 to WPB fusion sites. These findings indicate that Munc13-4 supports acute WPB exocytosis by tethering WPBs to the plasma membrane via AnxA2-S100A10.
A revisited Johnson–Mehl–Avrami–Kolmogorov model and the evolution of grain-size distributions in steel
Authors: Hömberg Dietmar , Patacchini Francesco Saverio , Sakamoto Kenichi , Zimmer Johannes
Published: April 2017

The classical Johnson–Mehl–Avrami–Kolmogorov approach for nucleation and growth models of diffusive phase transitions is revisited and applied to model the growth of ferrite in multiphase steels. For the prediction of mechanical properties of such steels, a deeper knowledge of the grain structure is essential. To this end, a Fokker–Planck evolution law for the volume distribution of ferrite grains is developed and shown to exhibit a log-normally distributed solution. Numerical parameter studies are given and confirm expected properties qualitatively. As a preparation for future work on parameter identification, a strategy is presented for the comparison of volume distributions with area distributions experimentally gained from polished micrograph sections.
Mechanisms of Possible Neurocognitive Dysfunction
Authors: Drane Daniel L. , Locke Dona E. C.
Published: April 2017

This chapter covers what is known about the possible mechanisms of neurocognitive dysfunction in patients with psychogenic nonepileptic seizures (PNES). It begins with a review of all research examining possible cognitive deficits in this population. Cognitive research in PNES is often obscured by noise created by a host of comorbid conditions (e.g., depression, post-traumatic stress disorder, chronic pain) and associated issues (e.g., effects of medications and psychological processes that can compromise attention or broader cognition). More recent studies employing performance validity tests raise the possibility that studies finding broad cognitive problems in PNES may be highlighting a more transient phenomenon secondary to these comorbid or secondary factors. Such dysfunction would likely improve with successful management of PNES symptomatology, yet the effects of even transient variability likely compromises daily function until these issues are resolved. Future research must combine the use of neuropsychological testing, performance validity measures, psychological theory, neuroimaging analysis, and a thorough understanding of brain–behavior relationships to address whether there is a focal neuropathological syndrome associated with PNES.
Practical and Diagnostic Challenges for the Neuropsychologist
Authors: Willment Kim , Loring David
Published: April 2017

The objective of this chapter is to outline practical and diagnostic challenges in the clinical neuropsychological evaluation of patients with psychogenic nonepileptic seizures (PNES) and to aid neuropsychologists in developing a consistent decision-making protocol. Challenges outlined include responding to performance validity test (PVT) failures, testing in different clinical environments, medications effects, acute psychological distress, and length of evaluations. Diagnostic challenges related to the neuropsychological evaluation in PNES, including the lack of specificity of cognitive profiles and psychopathological heterogeneity, are discussed. The final focus of the chapter is therapeutic goals of the neuropsychological evaluation, particularly the integration of the neuropsychological findings during the delivery of the PNES diagnosis and promoting cognitive self-efficacy.
Communicating the Diagnosis
Authors: Reuber Markus
Published: April 2017

Psychogenic nonepileptic seizures (PNES) can stop after the communication of the diagnosis by a healthcare professional, or PNES disorders can become more entrenched and patients are less able to control their seizures. This chapter addresses strategies for the explanation of the diagnosis of PNES, compares their effectiveness, and offers recommendations for delivering the diagnosis. A “positive” diagnostic label (such as “dissociative attacks”) may have advantages over a “negative” label (stating what the problem is not). Explaining PNES as a reflex response to potentially threatening triggers may be acceptable to PNES patients, who tend to experience PNES as a “physical” problem, while providing a rationale for psychological treatment interventions. However, PNES are a heterogeneous disorder and explanations have to be adapted to fit particular patients’ circumstances. How the diagnosis is communicated may be more important than what words are used for the disorder. Additional resources such as leaflets or websites may help patients understand their problem better. The explanation to patients should be followed by clear communication of the diagnosis to other health professionals involved in the patient’s care.
Readiness to Start Treatment and Obstacles to Adherence
Authors: Tolchin Benjamin , Baslet Gaston
Published: April 2017

Effective evidence-based psychotherapeutic regimens for psychogenic nonepileptic seizures (PNES) are available, but several obstacles still contribute to poor adherence to treatment. This chapter reviews the three stages at which patient dropout tends to occur in clinical practice and in studies. Patient-related, provider-related, and systemic causes of nonadherence are reviewed. Patient-related factors include a failure to accept or understand the diagnosis, psychiatric comorbidities, and ambivalence about change. Provider-related and systemic factors include a shortage of behavioral health specialists, gaps in care between neurologists and mental health providers, a lack of familiarity with the disorder, and stigmatization of patients. The chapter concludes with a review of potential interventions to address obstacles to treatment, including an integrated treatment team with joint presentation of the diagnosis, rapid and streamlined transition into psychotherapy, motivational interviewing, and engagement of patients’ family members and support systems.
An Integrated Approach to Other Functional Neurological Symptoms and Related Disorders
Authors: Stone Jon , Carson Alan
Published: April 2017

Patients with dissociative (nonepileptic) seizures (DS) commonly, although not always, present with comorbid somatic and psychological symptoms. This chapter reviews the epidemiology, diagnosis, and treatment of other functional somatic symptoms and disorders in relation to DS with a particular emphasis on other functional neurological symptoms such as movement disorder and sensory disturbance. Clinical assessment is presented as the start of treatment in patients with multiple functional symptoms including DS. The chapter discusses the importance of making a diagnosis of functional disorders, especially those in neurological settings, using positive evidence from the physical examination, such as Hoover’s sign for limb weakness or the tremor entrainment test for tremor. Practical methods of explaining these diagnoses to patients are reviewed, emphasizing the importance of transparency, educational materials, and presenting a model that focuses on mechanism more than etiology. The chapter concludes with a review of the evidence for treatment of a range of functional disorders often comorbid with DS.
Medical gases
Authors: Wiffen Philip , Mitchell Marc , Snelling Melanie , Stoner Nicola
Published: April 2017

This chapter is aimed at pharmacists and provides information on the different types of medical gases used for patient care within the hospital setting, and the different types of cylinders that such gases are supplied in. There is a brief description on the clinical uses of the different medical gases as a reference.
Patient management issues
Authors: Wiffen Philip , Mitchell Marc , Snelling Melanie , Stoner Nicola
Published: April 2017

This chapter outlines information relevant to pharmacists and other healthcare professionals on patient management issues related to special populations. It covers management of patients with liver impairment, including drug use, drug dosing, and hepatorenal syndrome. Drug use and dosing in renal impairment is discussed and the various methods of assessing or calculating glomerular filtration rate are reviewed. The use of drugs in pregnancy and breastfeeding is discussed with guidance given on assessing the risks versus benefits of drug use in these situations. Drugs and dietary considerations (including cultural considerations, food allergy and intolerance, and metabolic disorders), glucose-6-phosphate dehydrogenase deficiency and porphyria are discussed.
Patient-specific issues
Authors: Wiffen Philip , Mitchell Marc , Snelling Melanie , Stoner Nicola
Published: April 2017

This chapter covers patient-specific issues related to children, older people, injecting drug users, and surgical patients. For children, drug pharmacokinetics and pharmacodynamics and dose calculations are reviewed. The specific concerns around adherence and also medicines licensing in children are covered. For older people, the topics include pharmacokinetics, pharmacokinetics, and medication review. Guidance is given on managing injecting drug users, especially in an in-patient setting, including a suggested regimen for titration of methadone to avoid opioid withdrawal. For surgical patients, the topics covered include management of regular medicines during the nil-by-mouth period, drug interactions with perioperative drugs, and a brief description of the impact of selected drugs in the perioperative period.
Medicines management
Authors: Wiffen Philip , Mitchell Marc , Snelling Melanie , Stoner Nicola
Published: April 2017

This chapter outlines information relevant to clinical pharmacists related to medicines management. In particular, this chapter covers a variety of aspects for managing medicines, for example, formulary, unlicensed use, and medicines committees. It also includes guidance on standards and supervisory skills, as well as medicines safety and electronic prescribing. There are sections on non-medical prescribing, primary care, and roles of technicians.
Therapy-related issues: central nervous system
Authors: Wiffen Philip , Mitchell Marc , Snelling Melanie , Stoner Nicola
Published: April 2017

This chapter outlines information relevant to clinical pharmacists related to central nervous system issues and is loosely based on the British National Formulary, Chapter 4. In particular, this chapter covers issues related to pain and palliative care. Pain is defined and an algorithm for pain treatments is presented. A pain chart is illustrated with tips for monitoring pain and pain relief, and key concepts for treating acute, chronic, and cancer pains are described. This chapter also discusses the prevalence and treatment of depression, schizophrenia and psychosis, bipolar disorder, obsessive–compulsive disorder, and multiple sclerosis.
Therapy-related issues: endocrine
Authors: Wiffen Philip , Mitchell Marc , Snelling Melanie , Stoner Nicola
Published: April 2017

This chapter outlines information relevant to clinical pharmacists related to endocrine issues and is loosely based on the British National Formulary, Chapter 6. In particular, this chapter covers diabetes mellitus, both diagnosis and treatment, with a section on self-monitoring of blood glucose. There is also a section on thyroid disorders.
Aerobic trainability
Authors: McNarry Melitta A , Armstrong Neil
Published: April 2017

The key parameters of aerobic fitness are arguably peak oxygen uptake (V̇O2), pulmonary V̇O2 kinetics, blood lactate/ventilatory gas exchange thresholds, and exercise economy. The effects of training on these parameters are well-established in adults but, with the exception of peak V̇O2, data from children and adolescents are sparse and confounded by methodological and ethical issues. It has been hypothesized that children lack trainability due to the existence of a maturation threshold that must be surpassed before training adaptations manifest themselves. While a persuasive theoretical argument exists regarding the reality of a maturation threshold, there is no compelling empirical evidence to support it. The extrapolation of a training-induced increase in aerobic fitness to enhanced youth sport performance is complex, and sport-specific research models need to be developed and implemented. To determine the mechanisms underpinning aerobic trainability during youth, rigorous investigations utilizing recent advances in non-invasive technologies are required.
Medical screening
Authors: Wald Nicholas , Law Malcolm
Published: April 2017

Medical screening is the systematic application of a test or inquiry to identify individuals at sufficient risk of a specific disorder to benefit from further investigation or direct preventive action (these individuals not having sought medical attention on account of symptoms of that disorder). Key to this definition is that the early detection of disease is not an end in itself; bringing forward a diagnosis without altering the prognosis is useless and may be harmful....
Enterovirus infections
Authors: Minor Philip , Desselberger Ulrich
Published: April 2017

Enteroviruses are single-stranded, positive sense RNA viruses comprising poliomyelitis viruses (3 types), Coxsackie A viruses (23 types), Coxsackie B viruses (6 types), and echoviruses (33 types). They have recently been reclassified into 4 human enterovirus species (A–D) on the basis of sequence comparisons. Transmission is by the faeco-oral route, with marked seasonal peaks of infection in areas of temperate climate, but infections occurring all year round in tropical regions....
Staphylococci
Authors: Hota Bala , Popovich Kyle J. , Weinstein Robert A.
Published: April 2017

Staphylococci are Gram-positive cocci that form clusters, but can occur singly, in pairs, chains, or tetrads. They are classically distinguished from other Gram-positive cocci by presence of catalase, an enzyme that degrades hydrogen peroxide (H2O2). S. aureus is distinguished from other coagulase-negative staphylococci, which are generally less virulent, by the presence of coagulase, an enzyme that coagulates plasma. Many toxins and regulatory elements enhance virulence in staphylococci....
Melioidosis and glanders
Authors: Peacock S.J.
Published: April 2017

Melioidosis is a serious infection caused by the soil-dwelling Gram-negative bacillus Burkholderia pseudomallei. It is most commonly reported in north-east Thailand and northern Australia, but is increasingly recognized around the world. Infection is predominantly acquired through bacterial inoculation, often related to occupation, and mostly affects adults between the fourth and sixth decade who have risk factors such as diabetes mellitus and renal impairment....
Listeriosis
Authors: Hof H.
Published: April 2017

Listeriosis is caused by the Gram-positive bacillus Listeria monocytogenes, whose natural habitat is the soil. Consumption of soft cheeses, other dairy products, meat products, seafood, and vegetables is the principal route of infection. Patients at particular risk include those who are immunocompromised, very young, or very old. Pregnant women are also at risk, although they develop only mild disease, but the bacteria can be transmitted to the child either ...
Coxiella burnetii infections (Q fever)
Authors: Marrie T.J.
Published: April 2017

Q fever is a zoonosis caused by Coxiella burnetii, an intracellular Gram-negative spore-forming bacterium, the common animal reservoirs of which are cattle, sheep, and goats, although in a large outbreak in the Netherlands it appears that rats, Rattus norvegicus and R. rattus, may have played a role in the spread of the condition. ...
Fungal infections
Authors: Hay Roderick J.
Published: April 2017

The mycoses are disorders caused by fungi, which are saprophytic or parasitic organisms found in every continent and environment. Many are common commensals in nature, but others cause agricultural disease. The mycoses that are human infections include diseases ranging from those that are worldwide and common, such as dermatophytosis and candida infections, to those that are rare and often potentially life threatening, e.g. histoplasmosis. In humans, fungi usually adopt one of two morphologies: (1) the yeast form—where individual cells produce daughter cells by a process of budding and subsequently separate; or (2) the hyphal form—where cells do not separate but multiply to produce chains of cells joined end to end....
Cryptococcosis
Authors: Powderly William G.
Published: April 2017

Cryptococcus neoformans, which is found worldwide as a soil organism and thought to be transmitted by inhalation, most often causes disease in patients with abnormal cell-mediated immunity, notably patients with HIV infection and solid-organ transplant recipients, but the infection also occurs rarely in apparently immunocompetent people in restricted geographical areas, especially involving ...
Babesiosis
Authors: Brasseur Philippe
Published: April 2017

Babesia are intraerythrocytic, tick-transmitted, protozoan parasites that infect a broad range of wild and domesticated mammals including cattle, horses, dogs, and rodents. Human babesial infection is uncommon, caused by B. microti in North America and B. divergens in Europe, with most infections occurring in asplenic people. Presentation is typically with nonspecific ‘viral-type’ symptoms. Haemolytic anaemia is a characteristic feature and can be severe, particularly with ...
Toxoplasmosis
Authors: Liesenfeld Oliver , Petersen Eskild
Published: April 2017

Toxoplasma gondii is a protozoan parasite with worldwide distribution that infects up to one-third of the world’s population. Human infection is acquired through ingestion in water or food of oocysts shed by cats, or by ingestion of bradyzoites released from cysts contained in uncooked or undercooked meat (e.g. sheep, swine, cattle). Following invasion in the intestine, tachyzoites rapidly disseminate throughout the host. Immune mechanisms mediate the formation of cysts, primarily in the brain, eye, and skeletal and heart muscles, where they persist for the life of the host. Presence of infection may be established by direct detection of the parasite in clinical samples (often by polymerase chain reaction, PCR) or by serological techniques....
Nutrition: macronutrient metabolism
Authors: Frayn Keith N.
Published: April 2017

Food intake is sporadic: for most people it occurs in three major boluses each day. Energy expenditure, however, is continuous, with variations during the day that bear no resemblance to the pattern of energy intake, except that over some reasonable period of time (a week or more) the two will, in most people, match almost exactly. Therefore the body has developed complex systems that direct nutrients into storage pools when they are in excess, and that regulate the mobilization of nutrients from these pools as they are needed. The situation is analogous to the fuel tank of a car and the throttle that regulates fuel oxidation, except that in the car there is just one fuel and just one engine: in humans there are three major nutrients and a variety of tissues and organs, each of which may have its own preferences for fuels, that vary with time. Carbohydrate, fat, and protein (made up of amino acids), are the three sources of energy which are variably stored and assimilated from food each day. The fact that we can carry on our daily lives without thinking about whether to store or mobilize fuels, and which to use, attests to the remarkable efficiency of these control systems....
Diseases of overnourished societies and the need for dietary change
Authors: Mann J.I. , Truswell A.S.
Published: April 2017

The nutritional problems of a country depend more upon the stage of technical and economic development than geographical location. People in affluent societies do not have to worry about the problems of getting food and keeping it uninfected. Food is cheap for them, and they can eat their favourite foods all year round: the diet is energy-dense, high in fat and often also in sugar. There are multiple sources of nutritional advice and concerns, with breakthroughs and scares, science and pseudoscience, about all food....
Protein-dependent inborn errors of metabolism
Authors: Hoffmann Georg F. , Kölker Stefan
Published: April 2017

Protein-dependent inborn errors of metabolism are caused by inherited enzyme defects of catabolic pathways or intracellular transport of amino acids. Most result in an accumulation of metabolites upstream of the defective enzyme (amino acids and/or ammonia), causing intoxication.

Protein-dependent metabolic diseases usually have a low prevalence except for some high-risk communities with high consanguinity rates. However, the cumulative prevalence of these disorders is considerable (i.e. at least >1:2000 newborns) and represents an important challenge for all public health systems....
Glycogen storage diseases
Authors: Lee Philip , Bhattacharya Kaustuv
Published: April 2017

Glycogen metabolism is regulated by a number of different enzymes, defects in any of which result in several types of glycogen storage disease.

Types I, III, VI, and IX have predominantly hepatic manifestations: they typically present in infancy with failure to thrive and hepatomegaly, and they are associated with fasting hypoglycaemia. Diagnosis can be made in many cases by detection of gene mutation or functional tests of red blood cells or white blood cells. Most patients require an intensive dietary regimen providing a constant source of exogenous glucose, particularly in childhood. In illness, glucose requirements increase and it is necessary to continue to provide glucose either enterally or intravenously to prevent hypoglycaemia and secondary metabolic disturbances....
The porphyrias
Authors: Cox T.M.
Published: April 2017

The porphyrias are metabolic disorders characterized by overproduction of haem precursors, principally in the liver and bone marrow. Most porphyrias are inborn errors that affect enzymatic steps in a tightly regulated biosynthetic pathway for haem; acquired forms also occur.

Hepatic synthesis of haem undergoes rapid and wide oscillations, but haem formation for erythropoiesis is generally constant; it increases many fold as the erythron expands to meet the demands of blood loss or destruction, or as a consequence of ineffective erythropoiesis....
Lipid and lipoprotein disorders
Authors: Durrington P.N.
Published: April 2017

Lipids are a heterogeneous group of substances that are distinguished by their low solubility in water and their high solubility in nonpolar (organic) solvents. They are essential as energy stores and respiratory substrates, as structural components of cells, as vitamins, as hormones, for the protection of internal organs, for heat conservation, for digestion, and for lactation....
Hereditary haemochromatosis
Authors: Griffiths William J. H. , Cox T. M.
Published: April 2017

Haemochromatosis is a hereditary disorder generally caused by inappropriate absorption of iron by the small intestine which leads to iron deposition in the viscera, endocrine organs, and other sites, causing structural injury and impaired function. The most common form is classical adult haemochromatosis, but juvenile and neonatal forms are recognized, and several other genetic syndromes associated with iron storage have been identified; these may rarely involve specific tissues selectively, such as the lens of the eye or basal ganglia of the brain, or a characteristic range of tissues including the liver, heart, and endocrine system. Early-onset (juvenile) haemochromatosis has a predilection for the heart, pituitary gonadotrophs and the pancreatic islet—thus myocardial disease (which may be fatal if untreated), hypogonadism and diabetes mellitus are prominent features. Prompt diagnosis and depletion of tissue iron by chelating agents—and venesection where possible—may be life-saving. Unravelling the molecular genetics of haemochromatosis is underpinning promising new therapies for disorders of iron homeostasis....
Disorders of peroxisomal metabolism in adults
Authors: Wierzbicki Anthony S.
Published: April 2017

The peroxisome is a specialized organelle which employs molecular oxygen in the oxidation of complex organic molecules including lipids. Enzymatic pathways for the metabolism of fatty acids, including very long-chain fatty acids (VLCFA) enable this organelle to carry out β‎-oxidation in partnership with mitochondria. A peroxisomal pathway for isoprenoid lipids derived from chlorophyll, such as phytanic acid, utilizes ...
Amyloidosis
Authors: Pepys M.B. , Hawkins P.N.
Published: April 2017

Amyloidosis is the clinical condition caused by extracellular deposition of amyloid in the tissues. Amyloid deposits are composed of amyloid fibrils, abnormal insoluble protein fibres formed by misfolding of their normally soluble precursors. About 30 different proteins can form clinically or pathologically significant amyloid fibrils in vivo as a result of either acquired or hereditary abnormalities. Small, focal, clinically silent amyloid deposits in the brain, heart, seminal vesicles, and joints are a universal accompaniment of ageing. However, clinically important amyloid deposits usually accumulate progressively, disrupting the structure and function of affected tissues and lead inexorably to organ failure and death. No treatment yet exists which can specifically clear amyloid deposits, but intervention which reduces the availability of the amyloid fibril precursor proteins may lead to amyloid regression with clinical benefit....
Thyroid cancer
Authors: Weetman Anthony P.
Published: April 2017

Thyroid cancers account for less than 1% of all malignancies but are much the most frequent cancers of endocrine organs.

Follicular epithelial cell cancer—the commonest type; may be induced by exposure to radiation; can be highly undifferentiated or differentiate into recognizable follicular cells, sometimes with retention of hormone biosynthesis; typically present with an asymptomatic thyroid nodule; usually diagnosed by fine needle aspiration biopsy; treatment is typically by total or near total thyroidectomy, with radio-iodine then administered to remove any remaining thyroid tissue (followed by long-term thyroid replacement therapy)....
Small-bowel bacterial overgrowth
Authors: Schatz Richard A. , Toskes Phillip P.
Published: April 2017

Case History—A 78 yr old woman presenting with a five-year history of diarrhoea.

Updates

Pathogenesis—discussion of the possible role of proton pump inhibitors.

Diagnosis—comparison of lactulose hydrogen, glucose hydrogen, and 14C D-xylose breath tests; preliminary studies of circulating CdtB antibodies as a diagnostic tool....
Cancers of the gastrointestinal tract
Authors: Bridgewater J.A. , Pereira S.P.
Published: April 2017

Cancers of the gastrointestinal tract are one of the most rewarding interfaces in translational medicine—particularly on colorectal cancer—leading to greater understanding of the genetic mechanisms leading to cancer and the development of novel targeted therapies.

Diagnosis of gastrointestinal tract cancers is usually made or suspected at endoscopy, confirmed by biopsy....
Blood vessels and the endothelium
Authors: Vallance Patrick , Channon Keith
Published: April 2017

The blood vessel wall consists of the intima, the media, and the adventitia. Not all vessels have each layer, and the layers vary in size and structure between vessels. (1) The intima is made up of a single layer of endothelial cells on a basement membrane, beneath which—depending on vessel size—there may be a layer of fibroelastic connective tissue and an internal elastic lamina that provides both structure and flexibility. Embedded in the intima are pericytes. (2) The media is made up of smooth muscle cells, elastic laminae and extracellular matrix. (3) The adventitia is the outermost part of the vessel, composed mainly of fibroelastic tissue but also containing nerves, small feeding blood vessels (the vasa vasorum), and lymph vessels. The adventitia is directly related to the surrounding perivascular adipose tissue....
Electrocardiography
Authors: Houghton Andrew R. , Gray David
Published: April 2017

The ECG has been recognized as a valuable diagnostic tool since the end of the 19th century. The normal ECG waveform consists of P, QRS, and T waves (and sometimes U waves)—P waves result from atrial depolarization, QRS complexes from ventricular depolarization, and T waves from ventricular repolarization. The standard 12-lead ECG utilizes 4 limb electrodes and 6 precordial electrodes to generate 12 leads or ‘views’ of the heart’s electrical activity. There are six limb leads (termed I, II, III, aVR, aVL, and aVF) and six precordial leads (termed V1, V2, V3, V4, V5, and V6). Supplementary ‘views’ can be obtained by using additional leads, such as V7, V8, and V9 to assess the posterior aspect of the heart and right-sided chest leads to look for a right ventricular myocardial infarction....
Cardiac investigation—nuclear and other imaging techniques
Authors: Sabharwal Nikant , Kelion Andrew , Karamitsos Theo , Neubauer Stefan
Published: April 2017

Myocardial perfusion scintigraphy (MPS) provides physiological information about the coronary circulation, in contrast to the anatomical information provided by angiography.

Three radionuclide-labelled perfusion tracers are routinely used in single photon emission computed tomography (SPECT) imaging: thallium-201 and the technetium-99 m-labelled complexes sestamibi and tetrofosmin. Imaging is performed following tracer injection during stress (exercise or pharmacological) and at rest; comparison allowing determination of whether regional perfusion is normal, or if there is inducible hypoperfusion or infarction/scar....
Epidemiology and general pathophysiological classification of heart failure
Authors: McDonagh Theresa A , Guha Kaushik
Published: April 2017

Definition and classification—heart failure is a clinical syndrome caused by cardiac dysfunction, most commonly left ventricular systolic dysfunction (LVSD). Many epidemiological studies focus on characterizing the incidence and/or prevalence of LVSD, using cut off points ranging from less than 30% to less than 50%. Patients with heart failure symptoms or signs and normal or near normal LV function are often classified as having heart failure with preserved ejection fraction (HF-PEF), but there is no clear and generally accepted definition of this condition.
Epidemiology—estimates of incidence and prevalence are heavily influenced by definition. An echocardiographic study of a random sample of the general population aged 25–74 years in Glasgow (Scotland) estimated a prevalence of heart failure of 1.5%, with a further 1.4% having asymptomatic LVSD. Prevalence rises significantly with age, with a median age of first presentation in the mid seventies. Longitudinal data suggests that the incidence of heart failure has remained fairly stable over the last few decades, but prevalence is increasing as more people survive cardiovascular disease earlier in life.
Aetiology—determining the aetiology of heart failure in epidemiological studies is difficult: the commonest cause in the developed world is coronary artery disease, followed by hypertension, which predominates in those with a diagnosis of HF-PEF.
Prognosis and morbidity—data from the United States of America and the United Kingdom show the death rates of those admitted to hospital with a diagnosis of heart failure have a mortality of over 30% at one year. The outcome has improved in recent years, perhaps linked to the increased usage of angiotensin inhibitors and β‎-blockers. Heart failure accounts for around 5% of all adult general medical admissions, and in developed countries the condition consumes 1 to 2% of health care budgets.
Heart valve disease
Authors: Henein Michael
Published: April 2017

Rheumatic valve disease remains prevalent in developing countries, but over the last 50 years there has been a decline in the incidence of rheumatic valve disease and an increase in the prevalence of degenerative valve pathology in northern Europe and North America. In all forms of valve disease, the most appropriate initial diagnostic investigation is almost always the echocardiogram....
Myocarditis
Authors: Mason Jay W.
Published: April 2017

Myocarditis has many infectious and noninfectious aetiologies; in most regions, viral infections are the main cause, with notable exceptions such as Chagas myocarditis in South America. The condition often results in congestive heart failure and is a common cause of chronic dilated cardiomyopathy, and it can also present with chest pain and/or ventricular arrythmias....
The cardiomyopathies: hypertrophic, dilated, restrictive, and right ventricular
Authors: McKenna William J. , Elliott Perry
Published: April 2017

The term cardiomyopathy is used to describe heart muscle disease unexplained by abnormal loading conditions (hypertension, valve disease, etc.), congenital cardiac abnormalities, and ischaemic heart disease. The current classification is based on the predominant phenotype, i.e. hypertrophic, dilated, arrhythmogenic right ventricular, restrictive and unclassifiable (including left ventricular noncompaction), and—where possible—incorporating inheritance and genotype. Cardiomyopathies associated with systemic diseases are described in ...
Congenital heart disease in the adult
Authors: Thorne S. A.
Published: April 2017

Adults with congenital heart disease are a growing population, and now outnumber children with congenital heart disease in the United Kingdom. Many patients with repaired hearts can now, with specialist care, expect to live a normal or near normal lifespan. Other survivors have complex, surgically altered hearts and circulations that reflect the surgical and interventional practices of the preceding two decades. Their long-term outlook is unknown and they remain at lifelong risk of complications that may require further intervention. The organization of services to provide specialist care is key to their long-term survival....
Cardiac bypass and valve surgery
Authors: Cooper Graham
Published: April 2017

Coronary artery bypass grafting (CABG)—the two main indications for are for relief of symptoms, usually angina and/or breathlessness, that persist even with optimal medical therapy (OMT), and/or prognosis. There is a prognostic benefit of CABG in patients with large volumes of ischaemia (i.e. affecting >12% of the ventricular mass), and the benefit of revascularization increases with increasing volumes of ischaemia. The overall mortality for elective CABG in the United Kingdom is around 1% and has continued to fall over the last decade despite an increasingly adverse risk profile of patients undergoing surgery. In randomized trials and large propensity-matched cohort registries CABG, in comparison to percutaneous coronary intervention (PCI) even with drug-eluting stents, has been shown to improve survival and to reduce the subsequent risk of myocardial infarction and recurrent angina. Approximately 80% of patients are alive a decade after surgery of whom around 70% are still free from angina....
Peripheral arterial disease
Authors: Powell Janet , Davies Alun
Published: April 2017

The most common presentations of peripheral arterial disease are intermittent claudication and abdominal aortic aneurysm. In patients under 50 years of age the cause of disease is most likely to be genetic, congenital, immunological, infectious, or traumatic; over 50 years of age the principal risk factor is smoking....
Deep venous thrombosis and pulmonary embolism
Authors: Stein Paul D. , Matta Fadi
Published: April 2017

Deep venous thrombosis (DVT) is diagnosed in 1 to 2% of hospitalized patients, but is often silent and is found much more frequently at autopsy. Patients typically complain of pain and/or swelling of the leg, but often the diagnosis will be considered only when the physician detects unilateral leg swelling....
Diagnosis, assessment, and treatment of essential hypertension
Authors: Williams Bryan , Firth John D.
Published: April 2017

Essential hypertension is almost invariably symptomless, and usually detected by routine screening or opportunistic measurement of blood pressure. Key questions to answer in the assessment of a person presenting with an elevated blood pressure are: (1) Do they have hypertension, i.e. is the blood pressure persistently elevated? (2) Are there any associated clinical features that might warrant further evaluation to exclude secondary causes of hypertension? (3) Are there factors that might be contributing to an elevated blood pressure, including lifestyle or dietary factors or concomitant medication? (4) Is there any associated target organ damage or comorbidity that influences the overall cardiovascular disease risk and subsequent treatment of the patient?...