bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal solution and optimality condition of the Hunter-Saxton equation
Authors: Shen Chunyu
Published: February 2018

This paper is devoted to the optimal distributed control problem governed by the Hunter-Saxton equation with constraints on the control. We first investigate the existence and uniqueness of weak solution for the controlled system with appropriate initial value and boundary conditions. In contrast with our previous research, the proof of solution mapping is local Lipschitz continuous, which is one big improvement. Second, based on the well-posedness result, we find a unique optimal control and optimal solution for the controlled system with the quadratic cost functional. Moreover, we establish the sufficient and necessary optimality condition of an optimal control by means of the optimal control theory, not limited to the necessary condition, which is another major novelty of this paper. We also discuss the optimality conditions corresponding to two physical meaningful distributed observation cases.
Force-extension behavior of DNA in the presence of DNA-bending nucleoid associated proteins
Authors: Dahlke K. , Sing C. E.
Published: February 2018

Interactions between nucleoid associated proteins (NAPs) and DNA affect DNA polymer conformation, leading to phenomena such as concentration dependent force-extension behavior. These effects, in turn, also impact the local binding behavior of the protein, such as high forces causing proteins to unbind, or proteins binding favorably to locally bent DNA. We develop a coarse-grained NAP-DNA simulation model that incorporates both force- and concentration-dependent behaviors, in order to study the interplay between NAP binding and DNA conformation. This model system includes multi-state protein binding and unbinding, motivated by prior work, but is now dependent on the local structure of the DNA, which is related to external forces acting on the DNA strand. We observe the expected qualitative binding behavior, where more proteins are bound at lower forces than at higher forces. Our model also includes NAP-induced DNA bending, which affects DNA elasticity. We see semi-quantitative matching of our simulated force-extension behavior to the reported experimental data. By using a coarse-grained simulation, we are also able to look at non-equilibrium behaviors, such as dynamic extension of a DNA strand. We stretch a DNA strand at different rates and at different NAP concentrations to observe how the time scales of the system (such as pulling time and unbinding time) work in concert. When these time scales are similar, we observe measurable rate-dependent changes in the system, which include the number of proteins bound and the force required to extend the DNA molecule. This suggests that the relative time scales of different dynamic processes play an important role in the behavior of NAP-DNA systems.
Near-perfect terahertz wave amplitude modulation enabled by impedance matching in VO2 thin films
Authors: Zhu Hong-Fu , Du Liang-Hui , Li Jiang , Shi Qi-Wu , Peng Bo , Li Ze-Ren , Huang Wan-Xia , Zhu Li-Guo
Published: February 2018

We present a terahertz (THz) amplitude modulation method with near perfect E-field amplitude modulation depths that is based on impedance matching in VO2 thin films during the thermally induced insulator-metal transition (IMT). It was observed that the impedance matching-induced THz amplitude modulation was sensitive to the resistance switching characteristics of the VO2 thin films. By designing the VO2 thin films to have four orders of magnitude of change in resistance during the IMT, we experimentally achieved an E-field amplitude modulation depth of 94.5% (intensity modulation depth of 99.7%) between the insulator phase of VO2 and the impedance matching state, and an E-field amplitude modulation depth of 97.6% (intensity modulation depth of 99.94%) between the impedance matching state and the metallic phase of VO2 at 0.5 THz. The experimental results were consistent with the results of simulations based on the transmission matrix model.
Porin self-association enables cell-to-cell contact in
Providencia stuartii
floating communities
Authors: El-Khatib Mariam , Nasrallah Chady , Lopes Julie , Tran Que-Tien , Tetreau Guillaume , Basbous Hind , Fenel Daphna , Gallet Benoit , Lethier Mathilde , Bolla Jean-Michel , Pagès Jean-Marie , Vivaudou Michel , Weik Martin , Winterhalter Mathias , Colletier Jacques-Philippe
Published: February 2018

Significance

We report that porins, the main gateway for hydrophilic nutrients and ions into bacterial cells, assemble face-to-face in crystals, yielding dimers of trimers (DOTs). Further investigation suggests that DOTs could support cell-to-cell contact in the floating communities formed by
Providencia stuartii
, and could enable direct communication between adjacent cells. Self-matching steric zipper interactions are observed at the dimer interface, suggesting a means by which DOT formation could be restricted to cells of the same clonal origin.
Karyopherin α-3 is a key protein in the pathogenesis of spinocerebellar ataxia type 3 controlling the nuclear localization of ataxin-3
Authors: Sowa Anna Sergeevna , Martin Elodie , Martins Inês Morgado , Schmidt Jana , Depping Reinhard , Weber Jonasz Jeremiasz , Rother Franziska , Hartmann Enno , Bader Michael , Riess Olaf , Tricoire Hervé , Schmidt Thorsten
Published: February 2018

Significance

Ataxin-3 is the affected protein in the neurodegenerative disorder spinocerebellar ataxia type 3 (SCA3). Nuclear ataxin-3 has been linked to disease progression and formation of aggregates. Our present findings implicate karyopherin alpha 3 (KPNA3) in the in vitro transport of ataxin-3 and in the SCA3-related phenotypes inDrosophilaand mouse models. We have demonstrated that altering transport proteins has an effect on both pathogenic mechanisms (e.g., the intracellular localization and the formation of aggregates) and key features of ataxin-3 toxicity such as anxiety, total activity, and gait abnormalities. A better appreciation of this cellular mechanism can enhance our understanding of polyglutamine diseases and the role of nuclear/cytoplasmic compartments in toxicity and clearance of ataxin-3.
Slovenes: “a nation of owners of one of the three original European languages?”
Authors: Flere Sergej
Published: February 2018

The Slovene national movement of the late nineteenth century was based primarily on the myth of an eternal linguistic community, an essentialist position within historiography. The national development itself best fits into patterns described by Hroch and Gellner. Although most objective conditions for national constitution were met by 1929, it is not clear if subjective ones had been met by that time. World War II revitalized the nation-constitution process, particularly by warring Communist- and Catholic-supported political and military factions, both claiming to fight for a Slovene identity, while Communists also claimed to be fighting for a “Greater” (Megali) Slovenia. With the war's end, and Slovenia becoming a Yugoslav republic and expanding geographically, there was no doubt of a Slovene national identity, as understood by Connor, among the general population. However, important developments followed in nation-constitution after 1945, particularly upon gaining independence in 1991. The process need not be considered completed. Slovenes may be considered leaning towards a cultural type nation, with a cultural nucleus in an essentialist understanding of the Slovene language.
Interview with David Powley
Authors: Dix Ann
Published: February 2018

This interview with David Powley, one of the pioneers of dramatherapy, took place in May 2017 and was conducted by Ann Dix. It is one of a series of interviews where the founders of dramatherapy in the UK are invited to reflect on their experiences and the development of dramatherapy as a profession.
Biocompatibility of highly purified bovine milk‐derived extracellular vesicles
Authors: Somiya Masaharu , Yoshioka Yusuke , Ochiya Takahiro
Published: February 2018

Extracellular vesicles (EVs) deliver biologically active cargos from donor cells to recipient cells for intercellular communication. Since the existence of RNA cargo was discovered, EVs have been considered to be useful drug‐delivery systems. Specifically, EVs from bovine milk (mEV) are one of the most promising platforms, since bovine milk is a scalable source of EVs for mass production. However, it is still difficult to isolate pure EVs from bovine milk owing to the complexity of raw materials. Furthermore, the biocompatibility and immunotoxicity of mEVs are still unclear. In this study, we developed a new method for isolating bovine milk‐derived EVs by employing acid treatment and ultracentrifugation. Isolated mEVs are spherical in shape, measure 120 nm in diameter and contain typical EV marker proteins, such as tetraspanins. Compared with the previously reported method, our method can isolate purer mEVs. When mEVs are contacted with the mouse macrophage cell line Raw264.7, mEVs are readily taken up by the cells without a cytotoxic effect, suggesting that mEVs can deliver the cargo molecules into cells. While systemic administration of mEVs into mice resulted in the absence of systemic toxicity, certain types of cytokines were slightly induced. No anaphylaxis effect was observed after serial administration of mEVs in mice. Thus, mEVs isolated using our method are well tolerated in vivo and may be useful for the drug‐delivery application.
Class IIa histone deacetylases link cAMP signaling to the myelin transcriptional program of Schwann cells
Authors: Gomis-Coloma Clara , Velasco-Aviles Sergio , Gomez-Sanchez Jose A. , Casillas-Bajo Angeles , Backs Johannes , Cabedo Hugo
Published: February 2018

Schwann cells respond to cyclic adenosine monophosphate (cAMP) halting proliferation and expressing myelin proteins. Here we show that cAMP signaling induces the nuclear shuttling of the class IIa histone deacetylase (HDAC)–4 in these cells, where it binds to the promoter and blocks the expression of c-Jun, a negative regulator of myelination. To do it, HDAC4 does not interfere with the transcriptional activity of MEF2. Instead, by interacting with NCoR1, it recruits HDAC3 and deacetylates histone 3 in the promoter of c-Jun, blocking gene expression. Importantly, this is enough to up-regulate Krox20 and start Schwann cell differentiation program–inducing myelin gene expression. Using conditional knockout mice, we also show that HDAC4 together with HDAC5 redundantly contribute to activate the myelin transcriptional program and the development of myelin sheath in vivo. We propose a model in which cAMP signaling shuttles class IIa HDACs into the nucleus of Schwann cells to regulate the initial steps of myelination in the peripheral nervous system.
TAPAS: tool for alternative polyadenylation site analysis
Authors: Arefeen Ashraful , Liu Juntao , Xiao Xinshu , Jiang Tao
Published: February 2018

Motivation

The length of the 3′ untranslated region (3′ UTR) of an mRNA is essential for many biological activities such as mRNA stability, sub-cellular localization, protein translation, protein binding and translation efficiency. Moreover, correlation between diseases and the shortening (or lengthening) of 3′ UTRs has been reported in the literature. This length is largely determined by the polyadenylation cleavage site in the mRNA. As alternative polyadenylation (APA) sites are common in mammalian genes, several tools have been published recently for detecting APA sites from RNA-Seq data or performing shortening/lengthening analysis. These tools consider either up to only two APA sites in a gene or only APA sites that occur in the last exon of a gene, although a gene may generally have more than two APA sites and an APA site may sometimes occur before the last exon. Furthermore, the tools are unable to integrate the analysis of shortening/lengthening events with APA site detection.

Results

We propose a new tool, called TAPAS, for detecting novel APA sites from RNA-Seq data. It can deal with more than two APA sites in a gene as well as APA sites that occur before the last exon. The tool is based on an existing method for finding change points in time series data, but some filtration techniques are also adopted to remove change points that are likely false APA sites. It is then extended to identify APA sites that are expressed differently between two biological samples and genes that contain 3′ UTRs with shortening/lengthening events. Our extensive experiments on simulated and real RNA-Seq data demonstrate that TAPAS outperforms the existing tools for APA site detection or shortening/lengthening analysis significantly.

Availability and implementation

https://github.com/arefeen/TAPAS

Supplementary information

Supplementary data are available at Bioinformatics online.
Psychological research in amyotrophic lateral sclerosis: Past, present, and future
Authors: Watermeyer Tamlyn J. , Goldstein Laura H.
Published: February 2018

This chapter, of particular interest to those interested in psychological treatments for people with amyotrophic lateral sclerosis (ALS), outlines earlier work that sought to identify correlates of reduced well-being and quality of life in people with ALS and delineates possible targets for intervention. In this context, the chapter then evaluates several studies that have investigated psychological interventions for optimizing well-being in people with ALS and their caregivers. The chapter reviews current efforts to address the paucity of interventional research in this patient group, focusing on five therapies that have so far been evaluated for treatment efficacy. These therapies include hypnosis, mindfulness, cognitive behavioural therapy, expressive disclosure therapy, and dignity therapy. The main findings from these studies and their clinical implications for people with ALS and their families are discussed. Recommendations for future research are considered, together with a discussion of the implementation of such interventions in therapeutic or multidisciplinary settings.
Quality of life in ALS: What is it and how do we measure it?
Authors: Zaccheo Vincenzo , Simmons Zachary
Published: February 2018

Because of the limited range of treatments available for ALS, care is centred on maximizing quality of life (QoL). There is no universal definition of QoL, and no single instrument of choice with which to measure it. Health-related QoL (HRQOL) refers to physical and mental health status, whereas global QoL incorporates socioeconomic and existential factors outside the medical realm. Instruments for measuring may be generic or disease-specific. With the exception of bulbar function, QoL in patients with ALS is largely independent of physical strength and function, but is related to psychological and existential factors, and possibly to social supports, religiosity, and multidisciplinary clinic care. The ‘response shift’ phenomenon generally results in stable QoL over time in those with ALS. The choice of a QoL instrument depends on the goals of the user, and depends on whether it is being used for individual clinical care, measuring research outcomes, or assessing groups of individuals.
Complementary and alternative medicines and ALS
Authors: Palmieri Arianna , Pagnini Francesco , Gibbons Chris
Published: February 2018

Complementary and alternative medicines (CAMs) are medical practices and products that are not part of conventional medical practice, including drugs, diets, mind–body approaches, herbs, and exercises. Given the lack of conventional treatments, it is worth exploring alternative medicines, with the aim of improving the general well-being of the person with ALS. CAMs should be approached with an open attitude by the physicians, who can recognize the potential not only for the treatment itself, but also for re-establishing a sort of perceived control. Some of these treatments have provided interesting results. In particular, the uses of hypnosis and meditation have been explored more rigorously. Both approaches lead to an improvement of well-being and a reduction of psychological distress.
Resilience and coping strategies in ALS patients and caregivers
Authors: Felgoise Stephanie H. , Dube Michelle L.
Published: February 2018

The experience of living with amyotrophic lateral sclerosis (ALS) necessitates adaptation by the person living with ALS (PALS) and their caregiver. In the face of an incurable illness, many PALS and their caregivers report a significant decline in their physical and psychosocial-spiritual health, whereas others endure the illness with great fortitude and demonstrate positive adjustment and wellbeing. This heterogeneity in adjustment has led researchers to conjecture about why or how some people maintain their quality of life while others do not. Psychosocial processes that facilitate adjustment to ALS are coping and a variety of resilience factors including hope, optimism, social problem solving, spirituality and religiosity, and social support and relationship satisfaction. Therapeutic interventions that may foster resilience and coping in PALS and their caregivers include communication, dignity therapy, Buddhist psychology and mindfulness, social problem-solving therapy, constructivist grief therapy, and quality of life therapy (QOLT).
Cognitive and behavioural dysfunction in ALS and its assessment
Authors: Abrahams Sharon , Crockford Christopher
Published: February 2018

Cognitive and behavioural dysfunction in amyotrophic lateral sclerosis (ALS) occurs in up to half of patients with a spectrum from ALS with no cognitive or behavioural impairment to ALS with frontotemporal dementia (FTD). ~ 15% have a full blown ALS-FTD syndrome, while ~ 35% show milder and specific deficits on verbal fluency, executive and language functions and social cognition. Patients may show a behavioural syndrome that ranges from mild specific difficulties to changes that fulfil diagnostic criteria for behavioural variant-FTD. Apathy is the most prevalent symptom, but disinhibition, perseveration, loss of sympathy/empathy, and change in eating behaviour are also described. The importance of assessment is increasingly recognized. A distinction is made between brief assessment tools useful within ALS clinics and more extensive neuropsychological assessment by a qualified clinical neuropsychologist. Newly developed assessments specifically designed for ALS are available and will make valuable contribution to clinical care.
Neglected needs: Sexuality, intimacy, anger
Authors: Marconi Anna
Published: February 2018

ALS diagnosis and progression causes a series of major physical losses and emotional responses. Each patient reacts in a personal way, but the most common emotions during the initial stages are initiated by feelings of loss and by sentiments linked to grief. The first part of the chapter shows how emotions may follow one another during each stage of the disease. It subsequently provides an analysis of the sexuality construct and offers two case reports that show a representation of intimacy, especially tenderness, as an essential dimension for couples dealing with this disease. A good conjugal intimacy, intended as a physical and communicative relationship with no quarrelling, could guarantee the strength necessary to confront difficulties arising from ALS and to maintain quality of life in general. Finally, because health care professionals may find intimacy a difficult topic to discuss with a patient, it suggests four main points to consider.
Cardiovascular system
Authors: Coghlan J. Gerry , Schreiber Benjamin E.
Published: February 2018

Rheumatology, as a specialty that encounters many multisystem diseases, requires knowledge of many of the more exotic cardiovascular conditions including large- and small-vessel vasculitis, pulmonary hypertension, and myopericarditis. In addition, many rheumatology patients will suffer from cardiovascular pathology due to its common nature and association with an older population, since many previously lethal conditions are now associated with better survival. This requires a detailed knowledge of the drug—drug interactions that arise and the off-target consequences of rheumatological therapies that may aggravate atheroma and hypertension. The rheumatologist therefore needs a broad knowledge of cardiovascular diseases.
The kidney
Authors: Little Mark , Salama Alan
Published: February 2018

Kidney dysfunction is common in patients with rheumatological disease, be it secondary to renal (usually glomerular) involvement by a multisystem rheumatological disorder, renal impairment due to nephrotoxic medication use, or incidentally noted during a rheumatological work-up. It is therefore important for the rheumatologist to know how to assess kidney function biochemically and radiologically, to appreciate when an organ-threatening process is present, and to understand the basic steps to take in the event of acute kidney injury. This chapter reviews assessment of kidney function with respect to estimating excretory function, and the degree of proteinuria and haematuria. It provides an in-depth review of the causes, assessment, and management of acute kidney injury as encountered in rheumatological practice, and a summary of the causes and approach to chronic kidney disease.
Environment
Authors: Holroyd Christopher R. , Harvey Nicholas C. , Edwards Mark H. , Cooper Cyrus
Published: February 2018

Musculoskeletal disease covers a broad spectrum of conditions whose aetiology comprises variable genetic and environmental contributions. More recently it has become clear that, particularly early in life, the interaction of gene and environment is critical to the development of later disease. Additionally, only a small proportion of the variation in adult traits such as bone mineral density has been explained by specific genes in genome-wide association studies, suggesting that gene-environment interaction may explain a much larger part of the inheritance of disease risk than previously thought. It is therefore critically important to evaluate the environmental factors which may predispose to diseases such as osteorthritis, osteoporosis, and rheumatoid arthritis both at the individual and at the population level. In this chapter we describe the environmental contributors, across the whole life course, to osteoarthritis, osteoporosis and rheumatoid arthritis, as exemplar conditions. We consider factors such as age, gender, nutrition (including the role of vitamin D), geography, occupation, and the clues that secular changes of disease pattern may yield. We describe the accumulating evidence that conditions such as osteoporosis may be partly determined by the early interplay of environment and genotype, through aetiological mechanisms such as DNA methylation and other epigenetic phenomena. Such studies, and those examining the role of environmental influences across other stages of the life course, suggest that these issues should be addressed at all ages, starting from before conception, in order to optimally reduce the burden of musculoskeletal disorders in future generations.
Assessment of synovial joint fluid
Authors: Abdelattif Engy , Freemont Anthony J. , Mangham DC
Published: February 2018

Assessment of synovial joint fluid is a simple, cheap, and relatively non-invasive test that can be applied to the whole spectrum of joint diseases, provided there is sufficient fluid within the joint to aspirate. The chapter outlines the key steps in undertaking microscopic analysis of synovial fluid in order to maximize the diagnostic and prognostic return, while placing the features seen within the context of some of the most important joint diseases. The chapter also examines the changing face of microbiological examination of synovial fluid to diagnose joint infection as a primary event and also the increasingly important problem of infection secondary to joint replacement surgery.
Training and certification in acute cardiac care
Authors: Price Susanna , Gaevert Sofie , Sionis Alessandro , Bonnefoy Eric , Heras Magda
Published: February 2018

Advances in the treatment of cardiovascular diseases have changed their natural course and resulted in improved outcomes with prolongation of life. In parallel, subspecialization in cardiology has meant that training in the advanced management of critically ill cardiac patients to the level that is now required is no longer met within general cardiology. The growing demand for training in intensive cardiac care has led to the recognition of acute cardiac care as a subspecialty in its own right. This chapter describes the concept of clinical competence and its assessment within this challenging field. It also details the core curriculum and certification process established by the Acute Cardiovascular Care Association of the European Society of Cardiology to train and certify physicians in acute cardiac care.
Chest pain and chest pain units
Authors: Durand Eric , Chaib Aurès , Puymirat Etienne , Danchin Nicolas
Published: February 2018

Patients presenting at the emergency department with acute chest pain and suspected to represent an acute coronary syndrome were classically admitted as routine to the cardiology department, resulting in expensive and time-consuming evaluations. However, 2-5% of patients with acute coronary syndromes were discharged home inappropriately, resulting in increased mortality. To address the inability to exclude the diagnosis of acute coronary syndrome, chest pain units were developed, particularly in the United States. These provide an environment where serial electrocardiograms, cardiac biomarkers, and provocative testing can be performed to confirm or rule out an acute coronary syndrome. Eligible candidates include the majority of patients with non-diagnostic electrocardiograms. The results have been impressive; chest pain units have markedly reduced adverse events, while simultaneously increasing the rate of safe discharge by 36%. Despite evidence to suggest that care in chest pain units is more effective for such patients, the percentage of emergency or cardiology departments setting up chest pain units remains low in Europe.
Ethical issues in cardiac arrest and acute cardiac care: a European perspective
Authors: Vincent Jean-Louis
Published: February 2018

Acute cardiac syndromes are common and responsible for considerable mortality and morbidity. Decision making in such patients can be difficult clinically but can also be complex and challenging from an ethical perspective. This chapter reviews some of the ethical problems, including organ donation and withholding/withdrawing, that can occur in the acutely ill adult cardiac patient, starting with a brief look at the ethical principles that should guide our decision making: beneficence, non-maleficence, autonomy, and distributive justice. The role of advance directives and considerations related to family presence during cardiopulmonary resuscitation will also be discussed. With the increasing incidence and prevalence of coronary artery disease worldwide, the number of patients with cardiac arrest and requiring acute cardiac care is going to increase, and doctors will increasingly be faced with difficult ethical decisions associated with these patients. Open discussion and debate about these issues and good communication among patients, family members, and members of the health care team are essential to ensure that all patients receive the best possible end-of-life care.
Computed tomography angiography and other applications of computed tomography
Authors: de Graaf Michiel A , Scholte Arthur JHA , Kroft Lucia , Bax Jeroen J
Published: February 2018

Patients presenting with acute chest pain constitute a common and important diagnostic challenge. This has increased interest in using computed tomography for non-invasive visualization of coronary artery disease in patients presenting with acute chest pain to the emergency department; particularly the subset of patients who are suspected of having an acute coronary syndrome, but without typical electrocardiographic changes and with normal troponin levels at presentation. As a result of rapid developments in coronary computed tomography angiography technology, high diagnostic accuracies for excluding coronary artery disease can be obtained. It has been shown that these patients can be discharged safely. The accuracy for detecting a significant coronary artery stenosis is also high, but the presence of coronary artery atherosclerosis or stenosis does not imply necessarily that the cause of the chest pain is related to coronary artery disease. Moreover, the non-invasive detection of coronary artery disease by computed tomography has been shown to be related with an increased use of subsequent invasive coronary angiography and revascularization, and further studies are needed to define which patients benefit from invasive evaluation following coronary computed tomography angiography. Conversely, the implementation of coronary computed tomography angiography can significantly reduce the length of hospital stay, with a significant cost reduction. Additionally, computed tomography is an excellent modality in patients whose symptoms suggest other causes of acute chest pain such as aortic aneurysm, aortic dissection, or pulmonary embolism. Furthermore, the acquisition of the coronary arteries, thoracic aorta, and pulmonary arteries in a single computed tomography examination is feasible, allowing ‘triple rule-out’ (exclusion of aortic dissection, pulmonary embolism, and coronary artery disease). Finally, other applications, such as the evaluation of coronary artery plaque composition, myocardial function and perfusion, or fractional flow reserve, are currently being developed and may also become valuable in the setting of acute chest pain in the future.
Cardiac magnetic resonance in the intensive and cardiac care unit
Authors: Schwitter Juerg , Bremerich Jens
Published: February 2018

Current applications of cardiac magnetic resonance offer a wide spectrum of indications in the setting of acute cardiac care. In particular, cardiac magnetic resonance is helpful for the differential diagnosis of chest pain by the detection of ischaemia, myocardial stunning, myocarditis, and pericarditis. Also, Takotsubo cardiomyopathy and acute aortic diseases can be evaluated by cardiac magnetic resonance and are important differential diagnoses in patients with acute chest pain. In patients with restricted windows for echocardiography, according to guidelines, cardiac magnetic resonance is the method of choice to evaluate complications of an acute myocardial infarction. In an acute myocardial infarction, cardiac magnetic resonance allows for a unique characterization of myocardial damage by quantifying necrosis, microvascular obstruction, oedema (i.e. area at risk), and haemorrhage. These features will help us to understand better the pathophysiological events during infarction and will also allow us to assess new treatment strategies in acute myocardial infarction. To which extent the information on tissue damage will guide patient management is not yet clear, and further research, e.g. in the setting of the European Cardiovascular MR registry, is ongoing to address this issue. Recent studies also demonstrated the possiblity to reduce costs in the management of acute coronary syndromes when cardiac magnetic resonance is integrated into the routine work-up. In the near future, applications of cardiac magnetic resonance will continue to expand in the acute cardiac care units, as manufacturers are now strongly focusing on this aspect of user-friendliness. Finally, in the next decade or so, magnetic resonance imaging of other nuclei, such as fluorine and carbon, might become a reality in clinics, which would allow for metabolic and targeted molecular imaging with excellent sensitivity and specificity.
Non-invasive ventilation
Authors: Masip Josep , Planas Kenneth , Mas Arantxa
Published: February 2018

During the last 25 years, the use of non-invasive ventilation has grown substantially. Non-invasive ventilation refers to the delivery of positive pressure to the lungs without endotracheal intubation and plays a significant role in the treatment of patients with acute respiratory failure and in the domiciliary management of some chronic respiratory and sleep disorders. In the intensive and acute care setting, the primary aim of non-invasive ventilation is to avoid intubation, and it is mainly used in patients with chronic obstructive pulmonary disease exacerbations, acute cardiogenic pulmonary oedema, immunocompromised or in the context of weaning, situations in which a reduction in mortality has been demonstrated. The principal techniques are continuous positive airway pressure, bilevel pressure support ventilation and more recently, high flow nasal cannula. Whereas non-invasive pressure support ventilation requires a ventilator, the other two techniques are simpler and can be easily used in non-equipped areas by less experienced teams, including the pre-hospital setting. The success of non-invasive ventilation is related to an adequate timing, proper selection of patients and interfaces, close monitoring as well as the achievement of a good adaptation to patients’ demand.
Implanted cardiac support devices
Authors: Morley-Smith Andrew C , Simon André R , Pepper John
Published: February 2018

Mechanical circulatory support forms a crucial and expanding element of advanced heart failure management. Short-term assistance is delivered in emergency situations or where the underlying condition is likely to quickly worsen, and these approaches are discussed in Chapter 30. This chapter focuses on implantable devices intended for the medium and long term. The first half of the chapter is aimed directly at practical clinical management, whilst the second half considers the evidence base for contemporary practice. The chapter concludes by considering new paradigms for implantable cardiac support. Most frequently, these devices support left ventricular function (left ventricular assist devices), and this comprises the majority of our discussion.
Nutrition support in acute cardiac care
Authors: Casaer Michael P , Van den Berghe Greet
Published: February 2018

Malnutrition in cardiac and critical illness is associated with a compromised clinical outcome. The aim of nutrition therapy is to prevent these complications and particularly to attenuate lean tissue wasting and the loss of muscle force and of physical function. During the last decade, several well-powered randomized controlled nutrition trials have been performed. Their results challenge the existing nutrition practices in critically ill patients. Enhancing the nutritional intake and the administration of specialized formulations failed to evoke clinical benefit. Some interventions even provoked an increased mortality or a delayed recovery. These unexpected new findings might be, in part, caused by an important leap forward in the methodological quality in the recent trials. Perhaps reversing early catabolism in the critically ill patient by nutrition or anabolic interventions is impossible or even inappropriate. Nutrients effectively suppress the catabolic intracellular autophagy pathway. But autophagy is crucial for cellular integrity and function during metabolic stress, and consequently its inhibition early in critical illness might be deleterious. Evidence from large nutrition trials, particularly in acute cardiac illness, is scarce. Nutrition therapy is therefore focused on avoiding iatrogenic harm. Some enteral nutrition is administered if possible and eventually temporary hypocaloric feeding is tolerated. Above all, the refeeding syndrome and other nutrition-related complications should be prevented. There is no indication for early parenteral nutrition, increased protein doses, specific amino acids, or modified lipids in critical illness.
The use of biomarkers for acute cardiovascular disease
Authors: Jaffe Allan S
Published: February 2018

Understanding the proper use of biomarkers requires clinicians to appreciate some critical pre-analytic and analytic issues, as well as how to use the markers properly. The bene?ts of such an approach will not only facilitate the care of patients today, but will also prepare clinicians to understand and embrace the new generation of markers that is coming and that will continue to make this area transformational for cardiology. Two fundamental concepts underlie the clinical use of biomarkers: First, biomarkers should always be used in conjunction with all other clinical information. Second, in order to maximize their diagnostic and prognostic use, biomarkers should be interpreted as quantitative variables. For example, a cardiac troponin level which is 50 times the upper limit of normal has a much higher positive predictive value for the presence of an acute myocardial infarction, compared to a level just above the upper limit of normal.
Biomarkers in acute coronary syndromes
Authors: Giannitsis Evangelos , Katus Hugo A
Published: February 2018

Biomarker testing in the evaluation of a patient with acute chest pain is best established for cardiac troponins that allow the diagnosis of myocardial infarction, risk estimation of short- and long-term risk of death and myocardial infarction, and guidance of pharmacological therapy, as well as the need and timing of invasive strategy. Newer, more sensitive troponin assays have become commercially available and have the capability to detect myocardial infarction earlier and more sensitively than standard assays, but they are hampered by a lack of clinical specificity, i.e. the ability to discriminate myocardial ischaemia from myocardial necrosis not related to ischaemia such as myocarditis, pulmonary embolism, or decompensated heart failure. Strategies to improve clinical specificity (including strict adherence to the universal myocardial infarction definition and the need for serial troponin measurements to detect an acute rise and/or fall of cardiac troponin) will improve the interpretation of the increasing number of positive results. Other biomarkers of inflammation, activated coagulation/fibrinolysis, and increased ventricular stress mirror different aspects of the underlying disease activity and may help to improve our understanding of the pathophysiological mechanisms of acute coronary syndromes. Among the flood of new biomarkers, there are several novel promising biomarkers, such as copeptin that allows an earlier rule-out of myocardial infarction in combination with cardiac troponin, whereas MR-proANP and MR-proADM appear to allow a refinement of cardiovascular risk. GDF-15 might help to identify candidates for an early invasive vs conservative strategy. A multi-marker approach to biomarkers becomes more and more attractive, as increasing evidence suggests that a combination of several biomarkers may help to predict individual risk and treatment benefits, particularly among normal-troponin subjects. Future goals include the acceleration of rule-in and rule-out of patients with suspected acute coronary syndrome, in order to shorten lengths of stay in the emergency department, and to optimize patient management and the use of health care resources. New algorithms using high-sensitivity cardiac troponin assays at low cut-offs alone, or in combination with additional biomarkers, allow to establish accelerated rule-out algorithms within 1 or 2 hours.
Biomarkers in acute heart failure
Authors: Choudhary Rajiv , Shah Kevin , Maisel Alan
Published: February 2018

Acute heart failure continues to be a worldwide medical problem, associated with frequent readmissions, high mortality, and a profound economic impact on national health care systems. In the past decade, biomarkers have shifted the way in which acute heart failure is managed by the cardiologist. The search for the ideal biomarker to aid in the diagnosis, prognosis, and treatment of acute heart failure is ongoing. The natriureticfc peptides have proved extremely useful in determining whether acute dyspnoea has a cardiac aetiology. In addition, recent trials have demonstrated the use of natriuretic peptides in inpatient and outpatient prognosis, as well as in titrating medications in outpatients with chronic heart failure to prevent acute heart failure hospitalizations. Other emerging acute heart failure biomarkers include mid-regional pro-adrenomedullin, mid-regional proatrial natriuretic peptide, troponin, ST2, and neutrophil gelatinase-associated lipocalin.
Systems of care for patients with acute ST elevation myocardial infarction (STEMI networks)
Authors: Huber Kurt , Quinn Tom
Published: February 2018

Although primary percutaneous coronary intervention is the preferred strategy for patients with ST elevation myocardial infarction, offering a fast access to this procedure often remains difficult, because of local resources and capabilities and a lack of cooperation and organization. Accordingly, for most countries worldwide, primary percutaneous coronary intervention can be provided for only part of the population. Moreover, not all patients referred for primary percutaneous coronary intervention receive an optimal mechanical reperfusion within the recommended time intervals with the procedure performed in an experienced centre by an experienced team. Intravenous thrombolytic therapy, preferably administered pre-hospital and as part of a pharmacoinvasive strategy, offers a reasonable therapeutic option in selected cases. Network organization is central to offering fast and optimal reperfusion treatment in the individual case. It has been shown repeatedly that an early recognition of ST elevation myocardial infarction, as well as minimizing time delays, is important for the achievement of optimal clinical results. These findings should encourage the building up of regional networks, according to specific local constraints, and the monitoring of their effectiveness by ongoing registries. Financial, regulatory, and political barriers can be resolved, and a prompt guideline-recommended care becomes feasible and affordable if stakeholders and participants agree and cooperate.
Non-ST-segment elevation acute coronary syndromes
Authors: Bueno Héctor , Barrabés José A
Published: February 2018

Non-ST-segment elevation acute coronary syndromes are life-threatening disorders, usually caused by acute coronary thrombosis and subsequent myocardial ischaemia, presenting without persistent ST-segment elevation in the initial electrocardiogram. According to the occurrence of myocardial necrosis, non-ST-segment elevation acute coronary syndromes are divided into non-ST-segment myocardial infarction or unstable angina. The management of non-ST-segment elevation acute coronary syndromes requires an early diagnosis and risk stratification, urgent hospitalization, monitoring, and medical treatment, including antithrombotic therapy with dual antiplatelet therapy (aspirin plus one P2Y12 inhibitor) and parenteral anticoagulation, anti-ischaemic treatment, and preventative therapies. After the initial medical therapy is established, an invasive strategy, consisting of coronary angiography with coronary revascularization (either percutaneous coronary intervention or coronary bypass graft surgery), as appropriate, should be decided. The timing of the invasive strategy should be adjusted, according to the patient’s risk. Given the high event rate of patients with non-ST-segment elevation acute coronary syndromes after hospital discharge, an aggressive long-term preventative therapy should be put in place to improve prognosis.
Coronary artery bypass graft surgery
Authors: Davierwala Piroze M , Mohr Friedrich W
Published: February 2018

The surgical management of acute coronary syndrome still remains a challenge for the cardiac surgeon. Although most patients can be managed by percutaneous coronary intervention, for patients with complex multivessel or left main coronary artery disease (high SYNTAX score), in whom percutaneous coronary intervention is not possible or is unsuccessful, urgent or emergent coronary artery bypass graft surgery is the only available option. It is very important for surgeons to determine the optimum timing of surgical intervention, which is usually based on the clinical presentation, coronary anatomy, and biomarkers. Surgeons should be conversant with the different operative techniques, whether off- or on-pump coronary artery bypass graft surgery, that would help in achieving the best possible outcomes in such situations. Early and late survival of patients depends not only on an efficiently executed operation, but also on the competency of the post-operative care delivered. Modern perioperative management is reinforced by the availability of a variety of mechanical cardiopulmonary assist devices, like the intra-aortic balloon pump, the extracorporeal membrane oxygenation, and an array of ventricular assist devices, which aid us in managing very sick patients presenting with cardiogenic shock. The results of coronary artery bypass graft surgery for acute coronary syndrome, as published in the literature, vary significantly, because of the heterogeneity of patient populations, operative timing, and haemodynamic status, making a comparison of surgical outcomes almost impossible. Only one randomized trial has been conducted to that effect, to date. A heart team approach, involving an interventional cardiologist and a cardiac surgeon, is mandatory to determine the best treatment strategy and achieve the best possible outcomes in patients with acute coronary syndrome.
Cardiogenic shock in patients with acute coronary syndromes
Authors: Thiele Holger , Zeymer Uwe
Published: February 2018

Cardiogenic shock complicating an acute coronary syndrome is observed in up to 10% of patients and is associated with high mortality still approaching 50%. The extent of ischaemic myocardium has a profound impact on the initial, in-hospital, and post-discharge management and prognosis of the cardiogenic shock patient. Careful risk assessment for each patient, based on clinical criteria, is mandatory, to decide appropriately regarding revascularization by primary percutaneous coronary intervention or coronary artery bypass grafting, drug treatment by inotropes and vasopressors, mechanical left ventricular support, additional intensive care treatment, triage among alternative hospital care levels, and allocation of clinical resources. This chapter will outline the underlying causes and diagnostic criteria, pathophysiology, and treatment of cardiogenic shock complicating acute coronary syndromes, including mechanical complications and shock from right heart failure. There will be a major focus on potential therapeutic issues from an interventional cardiologist’s and an intensive care physician’s perspective on the advancement of new therapeutical arsenals, both mechanical percutaneous circulatory support and pharmacological support. Since studying the cardiogenic shock population in randomized trials remains challenging, this chapter will also touch upon the specific challenges encountered in previous clinical trials and the implications for future perspectives in cardiogenic shock.
Gender considerations in acute coronary syndromes
Authors: Swahn Eva , Alfredsson Joakim , Lawesson Sofia Sederholm
Published: February 2018

It is a very important issue to enlighten on gender differences and similarities regarding the management of patients with acute coronary syndromes. It is a fact that women have not been included in clinical trials in numbers equal to men, for whatever reason. In the future, it will be necessary to individualize, as much as possible, the management of patients, regardless of gender. To get there, it is necessary to have sufficient numbers of patients from both genders included in trials, or otherwise it is not possible to draw proper conclusions. Until now, most results regarding women and acute coronary syndromes have been based on substudy analyses with inadequate statistical power. If gender differences have become evident in studies with gender-mixed populations, it seems obvious that the calculated power to show significant differences is also inadequate for men. There is an urgent need of more research in this area, in order not to harm our patients with our treatment because of a paucity of knowledge. It is also as important not to withdraw proper treatment from certain individuals when they can benefit from it.