bluuebunny/crossref_metadata_2025 huggingface dataset:
Martin Luther in Norway
Authors: Rasmussen Tarald
Published: March 2017

Until 1814, Norway was under Danish rule, and the story of Luther’s reception in Norway is included in the story of Luther’s reception in Denmark (cf. Niels Henrik Gregersen’s article on Luther in Denmark). The Reformation was introduced in Norway in 1536 along with Danish rule and loss of Norwegian national sovereignty. Most pastors—some Danes, but gradually also more Norwegians—were educated at the University of Copenhagen and were strongly influenced by the training they received there.

In the period of national awakening in the 19th century, national identity and Lutheran identity were more difficult to combine in Norway than in neighboring Lutheran countries like Denmark, Sweden, or Germany. This period lasted quite long after 1814 until a specific tradition for Luther’s reception was established in Norway. Along with the Luther renaissance in Germany and Sweden in the 1920s and 1930s, a new interest in Luther and the Reformation also emerged in Norway. Luther texts (primarily texts from his early career) were translated into Norwegian, a Luther Society was established, and the first academic dissertation dealing with Luther’s theology was published. On the occasion of the 400th anniversary of the Reformation in Denmark/Norway, a comprehensive collection of essays was published in 1937 in order to reintroduce Luther and Reformation topics into religious and public debate. After World War II, scholarly research on Luther gradually increased in importance, and several Luther dissertations were published in international languages during the second half of the 20th century. In 1979 to 1983, six volumes of Luther’s writings were translated into Norwegian.
Luther, Lutheranism, and Post-Christianity
Authors: Hampson Daphne
Published: March 2017

It would not be possible to say that the Lutheran tradition has led to the post-Christian world that is Europe today, the causes of which must be multifarious. Nevertheless, it is thinkers in the Lutheran tradition, as in no other, who have tackled the question as to what the coming of modernity means for the truth of Christian claims. It may be said that Luther himself and those around him took a large step from a Catholic, Aristotelian world into modernity. In the Enlightenment, it was notably German thinkers who had come out of a Lutheran context among them, Immanuel Kant, G. W. F. Hegel, and Ludwig Feuerbach, who advanced a demythologized interpretation of scripture, seeing the Christian myth as a projection of human self-understanding; the form that their secularizing position took being profoundly influenced by their Lutheran context. Meanwhile, the basic paradigm of Lutheranism, a Christocentic faith set over against reason or works, allowed other Lutheran thinkers to proclaim a Christian apologetic in the face of the Enlightenment (Søren Kierkegaard), and 20th-century secularity (Rudolf Bultmann, Dietrich Bonhoeffer). The Lutheran Christocentric apologetic would seem to have ended in incoherence, or to have become irrelevant, in a post-Christian context. It fits ill with forms of post-Christian spirituality. This notwithstanding, it remains the case that ways of thinking that derive from Lutheran thought have profoundly affected the modern world, its philosophy, culture, and psychoanalytic thought. It should be a cause for admiration, not derision, that those who have stood in this tradition—from Luther forward—have been ready to face the intellectual issues of their day and the challenges posed to Christianity. This stands in marked contrast with the comparative failure of the Catholic tradition in this regard.
Drought and the Origins of the Mexican Revolution
Authors: Wolfe Mikael D.
Published: March 2017

What role did drought play in the outbreak of the Mexican Revolution of 1910? Although historians of the Mexican Revolution acknowledge that the effects of drought helped catalyze it, they have not explored in any depth what connects drought to revolution. Instead, they usually subsume it within a more general discussion of agricultural cycles to explain the conduct and fortunes of popular revolutionary armies. In particular, they reference the onset of drought between 1907 and 1909 as exacerbating an economic downturn induced by severe recession in the United States. By then, Mexico had become economically integrated with its northern neighbor through rapidly growing foreign investment, trade, and cross-border migration facilitated by the railroad transportation revolution. These socioeconomic and ecological factors together led to steep declines in wages and earnings, devastating crop failures, spikes in food prices (principally corn and beans), and even famine in the lower and middle classes.

Although suggestive, such passing references to drought in the historiography of the revolution do not furnish a clear picture of its effects and how they may have contributed to social and political conflict. In the 21st century, new technologies, methods, and sources—from historical meteorological reports and climate-related accounts gleaned from archival sources to modern historical climatological data reconstructions—facilitate doing more rigorous climate history. This article provides a sampling of these methods and sources on the role of drought in late 19th- and early 20th-century Mexico that can supplement, elucidate, and even revise our understanding of the origins of the Mexican Revolution.
Cardoso Presidency
Authors: Goertzel Ted
Published: March 2017

Fernando Henrique Cardoso (b. Rio de Janeiro, June 18, 1931) had an influential academic career before going into politics and becoming a senator, foreign minister, finance minister and president of Brazil. His book Dependency and Development in Latin America, co-authored with Enzo Faletto, was translated into several languages and was very widely cited. Cardoso’s academic career was interrupted by a military coup d’état in 1964, forcing him and many other left-leaning Brazilian academics into exile. In 1968 he was allowed to return to Brazil, where he and a number of colleagues started an applied research institute. When the military government began a gradual transition back to democracy, Cardoso joined a movement to rally the middle class and intelligentsia to pressure for direct elections to the presidency. Cardoso was elected an “alternate senator” on an opposition party ticket and later succeeded to the Senate. As a senator, he played a key role in the Constituent Assembly that wrote a new constitution for Brazil in 1988. In 1992, he left the Senate to take the position of minister of external relations. In 1993, President Itamar Franco unexpectedly prevailed on him to accept the position of finance minister. Much to everyone’s surprise, Cardoso and his team succeeded in ending hyperinflation and giving Brazil a stable currency without imposing austerity or hardship. The success of the monetary reform led to his election as president of Brazil in 1994. In 1998, he again won the presidency, but in his second term the economy went into decline, largely due to crises in Mexico, Russia, and elsewhere. In 2002 he passed the presidential sash on to Luiz Inácio Lula da Silva of the Workers Party. In retirement from the presidency, he continued to be active in the leadership of his political party, and served on many international boards and commissions. In 2016, he supported the impeachment of Dilma Rousseff for violations of fiscal responsibility laws.
Latin literature, popular
Authors: Graverini Luca
Published: March 2017

Any attempt at defining popular literature with some precision is fraught with difficulties. A flexible and pragmatic approach is the most rewarding, since it allows one to look at the subject from a few different viewpoints: “popular” can be understood as referring to the Roman people as a whole, or only to its lower social strata; a text can be defined as popular because it has been composed in a popular milieu, and/or because it addresses a popular audience. A mode of reception of literature can also be labelled “popular.” The traditional Roman elite only conceived literature as something useful, which could and should contribute to the instruction of its readers and to the well-being of the State. However, gradually a different attitude emerged: one that appreciated literature, and especially narrative, mostly or even only for its pleasurable and escapist qualities, sometimes even without any concern for its cultural sophistication.

This rather loose definition allows us to discern a popular streak in many literary forms. For example, it is often surmised that ancient drama addressed the Roman people as a whole, without distinction of social class or cultural level. Other forms of theatre, such as Atellanae, mime, and pantomime, had a more farcical nature and were especially favoured by a less sophisticated public, but at least on some occasions they made some demands on the education of their audiences and contributed to the diffusion of traditional Roman culture. Non-elite social classes had literary activities of their own, especially during the Empire, when literacy increased. These texts are extant especially thanks to epigraphical sources, and are often written in an unsophisticated and colloquial language. Narrative in its various forms could address very different audiences, but the possibility of reading a good tale for entertainment more than for instruction was always open, for sophisticated novels such as Apuleius’s Metamorphoses as well as for simpler tales and collections of mirabilia. Edifying Christian narratives were programmatically written in order to be understandable to and appreciated by a large and not necessarily cultured public, whose faith they intended to strengthen and promote. Playful poetry and didactic literature also had a space among midlevel literary activities.
revision in Greek and Latin literature
Authors: Gurd Sean Alexander
Published: March 2017

Revision happens when a text is changed. Its most common name in Greek was διόρθωσις; in Latin, emendatio. It was practised by writers of all styles and levels of ability, working alone and in consultation with others, and in many different genres. Evidence for revision comes from papyri and from descriptions in ancient literature. It occurred on papyri, in wax tablets, and in authors’ minds as they prepared a text, and it was understood by ancient writers as either the inevitable consequence of error or as a valuable exercise leading to greater cognitive and political skill. In addition to reminding us of the fluidity of textuality and the always contingent nature of every literary formation, the study of revision provokes reflection on the relationship between literature and natural language, and on writing’s place in social exchange.
The Acquisition of Color Words
Authors: Wagner Katie , Barner David
Published: March 2017

Human experience of color results from a complex interplay of perceptual and linguistic systems. At the lowest level of perception, the human visual system transforms the visible light portion of the electromagnetic spectrum into a rich, continuous three-dimensional experience of color. Despite our ability to perceptually discriminate millions of different color shades, most languages categorize color into a number of discrete color categories. While the meanings of color words are constrained by perception, perception does not fully define them. Once color words are acquired, they may in turn influence our memory and processing speed for color, although it is unlikely that language influences the lowest levels of color perception.

One approach to examining the relationship between perception and language in forming our experience of color is to study children as they acquire color language. Children produce color words in speech for many months before acquiring adult meanings for color words. Research in this area has focused on whether children’s difficulties stem from (a) an inability to identify color properties as a likely candidate for word meanings, or alternatively (b) inductive learning of language-specific color word boundaries. Lending plausibility to the first account, there is evidence that children more readily attend to object traits like shape, rather than color, as likely candidates for word meanings. However, recent evidence has found that children have meanings for some color words before they begin to produce them in speech, indicating that in fact, they may be able to successfully identify color as a candidate for word meaning early in the color word learning process. There is also evidence that prelinguistic infants, like adults, perceive color categorically. While these perceptual categories likely constrain the meanings that children consider, they cannot fully define color word meanings because languages vary in both the number and location of color word boundaries. Recent evidence suggests that the delay in color word acquisition primarily stems from an inductive process of refining these boundaries.
Flood Risk Analysis
Authors: Merz Bruno
Published: March 2017

Floods affect more people worldwide than any other natural hazard. Flood risk results from the interplay of a range of processes. For river floods, these are the flood-triggering processes in the atmosphere, runoff generation in the catchment, flood waves traveling through the river network, possibly flood defense failure, and finally, inundation and damage processes in the flooded areas. In addition, ripple effects, such as regional or even global supply chain disruptions, may occur.

Effective and efficient flood risk management requires understanding and quantifying the flood risk and its possible future developments. Hence, risk analysis is a key element of flood risk management. Risk assessments can be structured according to three questions: What can go wrong? How likely is it that it will happen? If it goes wrong, what are the consequences? Before answering these questions, the system boundaries, the processes to be included, and the detail of the analysis need to be carefully selected.

One of the greatest challenges in flood risk analyses is the identification of the set of failure or damage scenarios. Often, extreme events beyond the experience of the analyst are missing, which may bias the risk estimate. Another challenge is the estimation of probabilities. There are at most a few observed events where data on the flood situation, such as inundation extent, depth, and loss are available. That means that even in the most optimistic situation there are only a few data points to validate the risk estimates. The situation is even more delicate when the risk has to be quantified for important infrastructure objects, such as breaching of a large dam or flooding of a nuclear power plant. Such events are practically unrepeatable. Hence, estimating of probabilities needs to be based on all available evidence, using observations whenever possible, but also including theoretical knowledge, modeling, specific investigations, experience, or expert judgment. As a result, flood risk assessments are often associated with large uncertainties. Examples abound where authorities, people at risk, and disaster management have been taken by surprise due to unexpected failure scenarios. This is not only a consequence of the complexity of flood risk systems, but may also be attributed to cognitive biases, such as being overconfident in the risk assessment. Hence, it is essential to ask: How wrong can the risk analysis be and still guarantee that the outcome is acceptable?
Hydrodynamic Modeling of Urban Flood Flows and Disaster Risk Reduction
Authors: Sanders Brett F.
Published: March 2017

Communities facing urban flood risk have access to powerful flood simulation software for use in disaster-risk-reduction (DRR) initiatives. However, recent research has shown that flood risk continues to escalate globally, despite an increase in the primary outcome of flood simulation: increased knowledge. Thus, a key issue with the utilization of urban flood models is not necessarily development of new knowledge about flooding, but rather the achievement of more socially robust and context-sensitive knowledge production capable of converting knowledge into action. There are early indications that this can be accomplished when an urban flood model is used as a tool to bring together local lay and scientific expertise around local priorities and perceptions, and to advance improved, target-oriented methods of flood risk communication.

The success of urban flood models as a facilitating agent for knowledge coproduction will depend on whether they are trusted by both the scientific and local expert, and to this end, whether the model constitutes an accurate approximation of flood dynamics is a key issue. This is not a sufficient condition for knowledge coproduction, but it is a necessary one. For example, trust can easily be eroded at the local level by disagreements among scientists about what constitutes an accurate approximation.

Motivated by the need for confidence in urban flood models, and the wide variety of models available to users, this article reviews progress in urban flood model development over three eras: (1) the era of theory, when the foundation of urban flood models was established using fluid mechanics principles and considerable attention focused on development of computational methods for solving the one- and two-dimensional equations governing flood flows; (2) the era of data, which took form in the 2000s, and has motivated a reexamination of urban flood model design in response to the transformation from a data-poor to a data-rich modeling environment; and (3) the era of disaster risk reduction, whereby modeling tools are put in the hands of communities facing flood risk and are used to codevelop flood risk knowledge and transform knowledge to action. The article aims to inform decision makers and policy makers regarding the match between model selection and decision points, to orient the engineering community to the varied decision-making and policy needs that arise in the context of DRR activities, to highlight the opportunities and pitfalls associated with alternative urban flood modeling techniques, and to frame areas for future research.
Evolution of Agricultural Practices and the Transformation of the English Landscape
Authors: Williamson Tom
Published: March 2017

Agriculture has been the principal influence on the physical structure of the English landscape for many thousands of years. Driven by a wider raft of demographic, social, and economic developments, farming has changed in complex ways over this lengthy period, with differing responses to the productive potential and problems of local environments leading to the emergence of distinct regional landscapes. The character and configuration of these, as much as any contemporary influences, have in turn structured the practice of agriculture at particular points in time. The increasing complexity of the wider economy has also been a key influence on the development of the farmed landscape, especially large-scale industrialization in the late 18th and 19th centuries; and, from the late 19th century, globalization and increasing levels of state intervention. Change in agricultural systems has not continued at a constant rate but has displayed periods of more and less innovation.
Carbon Monoxide Releasing Molecules Blunt Placental Ischemia-Induced Hypertension
Authors: George Eric M , Cockrell Kathy , Arany Marietta , Stec David E , Rimoldi John M , Gadepalli Rama SV , Granger Joey P
Published: March 2017

BACKGROUND

Preeclampsia is a pregnancy complication which manifests as new-onset hypertension, proteinuria, and a spectrum of other symptoms. While the underlying causes are still a subject of much debate, it is commonly believed that placental ischemia is a central cause. The ischemic placenta secretes factors which are believed to be responsible for the maternal syndrome; most notably the anti-angiogenic protein soluble fms-like tyrosine kinase 1 (sFlt-1). We have reported that induction of the carbon monoxide (CO) producing protein heme oxygenase-1 restored angiogenic imbalance and reduced blood pressure in a rat model of placental ischemia, and that CO blocks hypoxia-induced sFlt-1 production from placental tissue in vitro. We therefore hypothesized that direct administration of CO by a CO-releasing molecule (CORM) would blunt the placental ischemia-induced increase in sFlt-1 and thus the hypertension characteristic of this model.

METHODS

We administered a soluble CO donor molecule (CORM-3) daily i.v. in control animals or those undergoing placental ischemia from GD14. Blood pressure and renal function were measured on GD19, and angiogenic markers measured by ELISA.

RESULTS

Interestingly, though we found that CORM administration significantly blunted the hypertensive response to placental ischemia, there was no concomitant normalization of sFlt-1 in either the placenta or maternal circulation. We did find, however, that CORM administration caused a significant increase in glomerular filtration rate, presumably by vasodilation of the renal arteries and increased renal plasma flow.

CONCLUSIONS

All in all these data suggest that administration of CO by CORMs do lower blood pressure during placental ischemia mechanisms independent of changes in angiogenic balance.
BEESEM: estimation of binding energy models using HT-SELEX data
Authors: Ruan Shuxiang , Swamidass S Joshua , Stormo Gary D
Published: March 2017

Motivation

Characterizing the binding specificities of transcription factors (TFs) is crucial to the study of gene expression regulation. Recently developed high-throughput experimental methods, including protein binding microarrays (PBM) and high-throughput SELEX (HT-SELEX), have enabled rapid measurements of the specificities for hundreds of TFs. However, few studies have developed efficient algorithms for estimating binding motifs based on HT-SELEX data. Also the simple method of constructing a position weight matrix (PWM) by comparing the frequency of the preferred sequence with single-nucleotide variants has the risk of generating motifs with higher information content than the true binding specificity.

Results

We developed an algorithm called BEESEM that builds on a comprehensive biophysical model of protein–DNA interactions, which is trained using the expectation maximization method. BEESEM is capable of selecting the optimal motif length and calculating the confidence intervals of estimated parameters. By comparing BEESEM with the published motifs estimated using the same HT-SELEX data, we demonstrate that BEESEM provides significant improvements. We also evaluate several motif discovery algorithms on independent PBM and ChIP-seq data. BEESEM provides significantly better fits to in vitro data, but its performance is similar to some other methods on in vivo data under the criterion of the area under the receiver operating characteristic curve (AUROC). This highlights the limitations of the purely rank-based AUROC criterion. Using quantitative binding data to assess models, however, demonstrates that BEESEM improves on prior models.

Availability and Implementation

Freely available on the web at http://stormo.wustl.edu/resources.html.

Supplementary information

Supplementary data are available at Bioinformatics online.
Removal of batch effects using distribution-matching residual networks
Authors: Shaham Uri , Stanton Kelly P , Zhao Jun , Li Huamin , Raddassi Khadir , Montgomery Ruth , Kluger Yuval
Published: March 2017

Motivation

Sources of variability in experimentally derived data include measurement error in addition to the physical phenomena of interest. This measurement error is a combination of systematic components, originating from the measuring instrument and random measurement errors. Several novel biological technologies, such as mass cytometry and single-cell RNA-seq (scRNA-seq), are plagued with systematic errors that may severely affect statistical analysis if the data are not properly calibrated.

Results

We propose a novel deep learning approach for removing systematic batch effects. Our method is based on a residual neural network, trained to minimize the Maximum Mean Discrepancy between the multivariate distributions of two replicates, measured in different batches. We apply our method to mass cytometry and scRNA-seq datasets, and demonstrate that it effectively attenuates batch effects.

Availability and Implementation

our codes and data are publicly available at https://github.com/ushaham/BatchEffectRemoval.git

Supplementary information

Supplementary data are available at Bioinformatics online.
Cardiovascular outcome trials in patients with chronic kidney disease: challenges associated with selection of patients and endpoints
Authors: Rossignol Patrick , Agarwal Rajiv , Canaud Bernard , Charney Alan , Chatellier Gilles , Craig Jonathan C , Cushman William C , Gansevoort Ronald T , Fellström Bengt , Garza Dahlia , Guzman Nicolas , Holtkamp Frank A , London Gerard M , Massy Ziad A , Mebazaa Alexandre , Mol Peter G M , Pfeffer Marc A , Rosenberg Yves , Ruilope Luis M , Seltzer Jonathan , Shah Amil M , Shah Salim , Singh Bhupinder , Stefánsson Bergur V , Stockbridge Norman , Stough Wendy Gattis , Thygesen Kristian , Walsh Michael , Wanner Christoph , Warnock David G , Wilcox Christopher S , Wittes Janet , Pitt Bertram , Thompson Aliza , Zannad Faiez
Published: March 2017

Although cardiovascular disease is a major health burden for patients with chronic kidney disease, most cardiovascular outcome trials have excluded patients with advanced chronic kidney disease. Moreover, the major cardiovascular outcome trials that have been conducted in patients with end-stage renal disease have not demonstrated a treatment benefit. Thus, clinicians have limited evidence to guide the management of cardiovascular disease in patients with chronic kidney disease, particularly those on dialysis. Several factors contribute to both the paucity of trials and the apparent lack of observed treatment effect in completed studies. Challenges associated with conducting trials in this population include patient heterogeneity, complexity of renal pathophysiology and its interaction with cardiovascular disease, and competing risks for death. The Investigator Network Initiative Cardiovascular and Renal Clinical Trialists (INI-CRCT), an international organization of academic cardiovascular and renal clinical trialists, held a meeting of regulators and experts in nephrology, cardiology, and clinical trial methodology. The group identified several research priorities, summarized in this paper, that should be pursued to advance the field towards achieving improved cardiovascular outcomes for these patients. Cardiovascular and renal clinical trialists must partner to address the uncertainties in the field through collaborative research and design clinical trials that reflect the specific needs of the chronic and end-stage kidney disease populations, with the shared goal of generating robust evidence to guide the management of cardiovascular disease in patients with kidney disease.
Spatial patterns of phytoplankton composition and upper-ocean biogeochemistry do not follow carbonate chemistry gradients in north-west European Shelf seas
Authors: Ribas-Ribas M. , Cripps G. L. , Townend M. , Poulton A. J. , Tyrrell T.
Published: March 2017

A key difficulty in ocean acidification research is to predict its impact after physiological, phenotypic, and genotypic adaptation has had time to take place. Observational datasets can be a useful tool in addressing this issue. During a cruise in June–July 2011, measurements of upper-ocean biogeochemical variables, climatically active gases and plankton community composition were collected from northwestern European seas. We used various multivariate statistical techniques to assess the relative influences of carbonate chemistry and other environmental factors on these response variables. We found that the spatial patterns in plankton communities were driven more by nutrient availability and physical variables than by carbonate chemistry. The best subset of variables able to account for phytoplankton community structure was the euphotic zone depth, silicic acid availability, mixed layer average irradiance, and nitrate concentration (59% of variance explained). The spatial variations in phytoplankton and coccolithophores species composition were both found to be more strongly associated with nutrients and physical variables than carbonate chemistry, with the latter only explaining 14 and 9% of the variance, respectively. The plankton community composition and contribution of calcifying organisms was not observed to change under lower calcite saturation state (Ω) conditions, although no regions of undersaturation (Ω < 1) were encountered during the cruise. Carbonate chemistry played a more prominent, but still secondary, role in determining dinoflagellate and diatom assemblage composition (20 and 13% of total variance explained, respectively). Nutrient and physical variables also explained more of the spatial variations of most climatically active gases and selected biogeochemical response variables, although some also appeared to be influenced by carbonate chemistry. This observational study has demonstrated that ocean acidification research needs to be set in context with other environmental forcing variables to fully appreciate the primary, or indeed secondary, role that increasing fugacity of carbon dioxide has on biological communities and associated biogeochemical rates.
Low Back Pain and Radicular Pain
Authors: Huntoon Marc A.
Published: March 2017

Low back pain is one of the most common pain syndromes in the world and a leading cause of disability and physician visits. Although degenerative disc disease and zygapophyseal joint spondylotic changes are common and lead to more permanent problems such as spinal stenosis, the interplay of biological and psychosocial factors is largely key to the chronification of many back pain disorders.
Structure and cell biology of the vessel wall
Authors: van Thiel Bibi S. , van der Pluijm I. , Kanaar Roland , Danser A.H. Jan , Essers Jeroen
Published: March 2017

The purpose of this chapter is to provide a general overview on the structure and composition of blood vessels. Moreover, the cellular constituents of the vessel wall, as well as the different types of blood vessels, are discussed. In addition the effect of ageing on the vascular wall and its role in the pathogenesis of vascular disease is discussed. More detailed insights into the pathogenesis of specific diseases, including atherosclerosis and aneurysms, are provided in other chapters of this book.
Animal models to study pathophysiology of the vasculature
Authors: Gu Wenduo , Xie Yao , Xu Qingbo
Published: March 2017

Animal models are designed to be preliminary tools for a better understanding of the pathogenesis, improvement in diagnosis, prevention, and therapy of vascular diseases in humans. Animal models are easily manageable, as compounding effects of dietary and environmental factors can be controlled experimentally. Blood vessel samples can be taken for detailed experimental and biomolecular examination. A thorough understanding of the animal models used is necessary and complete analysis must be validated so that the data can be extrapolated to humans. There are several species that are used for studying vascular pathophysiology, including mice, rats, rabbits, and pigs. Attracted by the well-defined genetic systems, a number of investigators have begun to use the mouse as an experimental system for arteriosclerosis research. Because vascular disorder is a complicated disease, which includes spontaneous (native) atherosclerosis, transplant arteriosclerosis, vein graft atherosclerosis, and angioplasty-induced restenosis, several models for studying all types of vascular disease have recently been established. Using these animal models, much knowledge concerning the pathogenesis of the disease and therapeutic intervention has been gained. This chapter will not attempt to cover all aspects of animal models, but will rather focus on the major progress in understanding the pathophysiology of the vasculature, the (dis)advantages of a variety of models, and how specific models can be appropriately chosen for different purposes of study.
The endothelial cell
Authors: Fleming Ingrid , Kwak Brenda R. , Meens Merlijn J.
Published: March 2017

The endothelium, a monolayer of cells that lines blood vessels, acts as a physical barrier between circulating blood and vascular smooth muscle cells. The purpose of this chapter is to provide a general overview on the structural heterogeneity of the endothelium. Moreover, the most important physiological functions of the vascular endothelium in blood vessels are discussed. More detailed insights into the pathogenesis of specific diseases, including atherosclerosis and hypertension, are provided in other chapters of this book.
The lymphatic system
Authors: Karaman Sinem , Aspelund Aleksanteri , Detmar Michael , Alitalo Kari
Published: March 2017

The lymphatic vascular system is an integral component of the circulatory system; it forms a one-way conduit that transports tissue interstitial components back to the venous circulation through lymph nodes. Lymphatic vessels extend to most tissues and contribute to the regulation of interstitial fluid homeostasis, trafficking of immune cells, and absorption of dietary fats from the gut. Developmentally, lymphatic vessels originate from embryonic veins and specialized angioblasts. A number of molecules have been identified in the commitment of endothelial cells to the lymphatic lineage, and the sprouting, expansion and maturation of the lymphatic vascular tree. Importantly, the vascular endothelial growth factor (VEGF) family members VEGFC and VEGFD, together with their receptors VEGFR2 and VEGFR3 have been implicated as critical regulators of lymphangiogenesis. Lymphatic vessels are involved in several human diseases, including cancer, where they contribute to tumour metastasis, the leading cause of cancer-related deaths. Lymphatic vessels regulate immune responses against foreign pathogens by transporting leucocytes to lymph nodes, but are also in involved in the regulation of self-tolerance. Defects in the lymphatic vascular system are causal for the development of lymphoedema.
Valvular heart disease
Authors: Kovanen Petri T. , Bäck Magnus
Published: March 2017

The heart valves, which maintain a unidirectional cardiac blood flow, are covered by endothelial cells and structurally composed by valvular interstitial cells and extracellular matrix. Valvular heart disease can be either stenotic, causing obstruction of the valvular flow, or regurgitant, referring to a back-flow through the valve. The pathophysiological changes in valvular heart disease include, for example, lipid and inflammatory cell infiltration, calcification, neoangiogenesis, and extracellular matrix remodelling. The present chapter addresses the biology of the aortic and mitral valves, and the pathophysiology of aortic stenosis and mitral valve prolapse.
Pathophysiology of thrombosis
Authors: Badimon Lina , Tanner Felix C. , Camici Giovanni G. , Vilahur Gemma
Published: March 2017

Ischaemic heart disease and stroke are major causes of death and morbidity worldwide. Coronary and cerebrovascular events are mainly a consequence of a sudden thrombotic occlusion of the vessel lumen. Arterial thrombosis usually develops on top of a disrupted atherosclerotic plaque because of the exposure of thrombogenic material, such as collagen fibrils and tissue factor (TF), to the flowing blood. TF, either expressed by subendothelial cells, macrophage- and/or vascular smooth muscle-derived foam-cells in atherosclerotic plaques, is a key element in the initiation of thrombosis due to its ability to induce thrombin formation (a potent platelet agonist) and subsequent fibrin deposition at sites of vascular injury. Adhered platelets at the site of injury also play a crucial role in the pathophysiology of atherothrombosis. Platelet surface receptors (mainly glycoproteins) interact with vascular structures and/or Von Willebrand factor triggering platelet activation signalling events, including an increase in intracellular free Ca2+, exposure of a pro-coagulant surface, and secretion of platelet granule content. On top of this, interaction between soluble agonists and platelet G-coupled protein receptors further amplifies the platelet activation response favouring integrin alpha(IIb)beta(3) activation, an essential step for platelet aggregation. Blood-borne TF and microparticles have also been shown to contribute to thrombus formation and propagation. As thrombus evolves different circulating cells (red-blood cells and leukocytes, along with occasional undifferentiated cells) get recruited in a timely dependent manner to the growing thrombus and further entrapped by the formation of a fibrin mesh.
Vascular pathophysiology of hypertension
Authors: Guzik Tomasz J. , Touyz Rhian M.
Published: March 2017

Hypertension is a multifactorial disease, in which vascular dysfunction plays a prominent role. It occurs in over 30% of adults worldwide and an additional 30% are at high risk of developing the disease. Vascular pathology is both a cause of the disease and a key manifestation of hypertension-associated target-organ damage. It leads to clinical symptoms and is a key risk factor for cardiovascular disease. All layers of the vascular wall and the endothelium are involved in the pathogenesis of hypertension. Pathogenetic mechanisms, whereby vascular damage contributes to hypertension, are linked to increased peripheral vascular resistance. At the vascular level, processes leading to change sin peripheral resistance include hyper-contractility of vascular smooth muscle cells, endothelial dysfunction, and structural remodelling, due to aberrant vascular signalling, oxidative and inflammatory responses. Increased vascular stiffness due to vascular remodelling, adventitial fibrosis, and inflammation are key processes involved in sustained and established hypertension. These mechanisms are linked to vascular smooth muscle and fibroblast proliferation, migration, extracellular matrix remodelling, calcification, and inflammation. Apart from the key role in the pathogenesis of hypertension, hypertensive vasculopathy also predisposes to atherosclerosis, another risk factor for cardiovascular disease. This is linked to increased transmural pressure, blood flow, and shear stress alterations in hypertension, as well as endothelial dysfunction and vascular stiffness. Therefore, understanding the mechanisms and identifying potential novel treatments targeting hypertensive vasculopathy are of primary importance in vascular medicine.
Adventitia and perivascular adipose tissue—the integral unit in vascular disease
Authors: Yang Zhihong , Ming Xiu-Fen
Published: March 2017

Obesity and obesity-associated metabolic disorders are highly associated with cardiovascular disease. Abnormal ectopic deposition and accumulation of adipose tissue in organs, including perivascular space (perivascular adipose tissue, PVAT) in obesity are emerging to contribute to vascular disease development through pathological paracrine and/or endocrine secretion of cytokines, namely adipokines, which are vasoactive factors including vascular relaxing and contracting factors, smooth muscle growth promoting and inhibiting factors, and pro- and anti-inflammatory factors. In obesity, production of these factors from PVAT is altered and in imbalance which favours vascular contraction, pathological remodelling, and inflammation. In cross-talk with the endothelium, the functional changes of adventitia and PVAT are detrimental and importantly contribute to the acceleration of vascular atherosclerosis and complications associated with obesity and metabolic disorders
Neurobiology of Fetal Alcohol Spectrum Disorders
Authors: Lopez-Arvizu Carmen , Bogle Carmel , Belcher Harolyn M.E.
Published: March 2017

Prenatal exposure to ethanol can result in a wide range of clinical presentations that are grouped under the term “Fetal Alcohol Spectrum Disorders” (FASD). The direct cellular teratogenic effects of ethanol on fetal neurodevelopment include damage to cell survival, proliferation, and migration mechanisms. Dysregulation of neurotransmission and alteration of genetic transcription have also been implicated in the neurotoxic effects of prenatal ethanol exposure. These deleterious events lead to brain volume reduction, corpus callosum dysgenesis, cerebellar, and other neuroanatomical anomalies that have been observed in individuals with FASD. Beyond direct ethanol-induced insults, the impact that ethanol has on maternal nutrition, metabolism, hormonal regulation, and placental physiology also adversely effects fetal development. The complex interactions between numerous neurobiological and psychosocial mechanisms that hinder optimal fetal neurodevelopment are reflected by the heterogeneous clinical presentation of FASD, including impaired growth, dysmorphic facial features, and cognitive and behavioral disorders.
Letter to Alexander Luria
Authors: Winnicott Donald W.
Published: March 2017

In this letter, Winnicott, who had met Luria at a conference in Copenhagen, asks if his work The First Year of Life might be published in Russian.
The Family and Emotional Maturity
Authors: Winnicott Donald W.
Published: March 2017

In this paper, Winnicott discusses the idea of maturity as a maturity appropriate for a particular age. An intact family is fundamental to healthy development and if the family is threatened this becomes very clear. For each family the actual father and mother are alive in the inner psychic reality of the children. But individuals need to become independent of their families for psychic health. Adult political institutions unconsciously reproduce home and family constellations. Children carry unconscious dependence on their actual father and mother, and it is within this dependence that the growing child’s need for independence can be safely asserted. An important feature of emotional development and maturity is the individual’s capacity, after acting out, to rediscover the original maternal care, parental provision and family stability, on which that individual was dependent in the early stages of life.
String: A Technique of Communication
Authors: Winnicott Donald W.
Published: March 2017

In this essay, Winnicott describes his work with a seven-year-old boy in the Psychology Department of the Paddington Green Children’s Hospital. Winnicott noticed the boy’s preoccupation with string and tying things together and described it to the mother as an attempt by the boy to master his fear of separation, a separation deriving from his early emotional life, the mother’s absence for the birth of his sister and the mother’s own depression. This is a case where the parents acted as therapists to the child since sessions with Winnicott were impossible.
Adolescence: Struggling Through the Doldrums
Authors: Winnicott Donald W.
Published: March 2017

In this talk to London County Council Children’s Department senior staff, Winnicott describes the features of adolescence that he believes are important for this audience of his to attend to. He speaks of each adolescent having to negotiate this age-specific phase, whilst also dealing with the onset of puberty, so as to arrive at adulthood. He is aware that adolescent breakdowns put a strain on society and require toleration and treatment. For Winnicott, three social developments have altered the climate of adolescence: treatment for venereal disease, the availability of contraceptive techniques, and the creation of the atom bomb, all of which affects the relationship between adult society and adolescence. The adolescent is pre-potent, and does not accept false solutions. The real cure for adolescence is the passage of time, and to get through this development stage, there will be a period Winnicott calls the adolescent doldrums.
Varieties of Psychotherapy
Authors: Winnicott Donald W.
Published: March 2017

In this talk to an association concerned with the social and medical aspects of mental illness, Winnicott addresses varieties of illness and varieties of therapy. He describes taking good case histories, listening very carefully, and using psychoanalytic tools (like transference and enabling the patient to say whatever comes to mind), and he states that therapy will involve addressing a setback or hitch in the emotional development of the individual. He defines three categories of patient: the psychoneurotic, those who experience early failure of care and the deprived. He indicates how psychotherapy can help in such categories of patient difficulty.
Letter to Dr Joan FitzHerbert
Authors: Winnicott Donald W.
Published: March 2017

In this letter, Winnicott disagrees with Dr FitzHerbert on the subject of extra-sensory perception.
Comments on ‘Problems of Research in Psycho-Analysis’
Authors: Winnicott Donald W.
Published: March 2017

Winnicott responds to a presentation by Sandler on the relationship between scientific research and psychoanalysis and whether psychoanalysis can usefully contribute to scientific research. He quotes Bion, suggesting that psychoanalysis, like science, has to attempt to understand its own dimensions and the meaning of research. Winnicott refers to a case of his own where a psychotic boy is experimenting with and testing reality, as it were, scientifically. He proposes that science is an intellectual study and must be ‘belief free’, whereas the psychoanalyst (though both disciplines ask questions creatively) tests his work against his personal beliefs. Winnicott refers to his work on transitional objects, where perception and apperception, in Sandler’s terms, do not apply. Rather, the self establishes what feels ‘real’ emotionally, even though this may be accepted as illusory. He asks if Sandler accepts this last idea.
Sakari: A Therapeutic Consultation
Authors: Winnicott Donald W.
Published: March 2017

In these notes on and squiggles from a child consultation carried out in Finland and assisted by an interpreter, Winnicott gives an account of the squiggle game that takes place between himself and the child, without offering a specific diagnosis.
Review: The Psychoanalytic Study of the Child, Volume 15
Authors: Winnicott Donald W.
Published: March 2017

In his review of the fifteenth volume of this yearly publication, Winnicott expresses his enthusiasm for the work and its continuing high standards.
Letter to Benjamin Spock
Authors: Winnicott Donald W.
Published: March 2017

In this letter to Benjamin Spock, Winnicott says that analysts must include the infant’s interest in transitional objects in their concept of normality and emphasizes the importance of studying the infant-mother relationship in the development of the child.
Training for Child Psychiatry
Authors: Winnicott Donald W.
Published: March 2017

In this contribution to a symposium on the training for child psychiatry—a new specialty in medicine at this time—Winnicott proposes that doctors who have trained in paediatrics and psychoanalysis should also train as child psychiatrists. Becoming an adult psychiatrist who then trains in child psychiatry is not advisable because the trainee doctor will have missed the development of child physical and emotional health during its maturation.
The Theory of the Parent-Infant Relationship: Contributions to Discussion
Authors: Winnicott Donald W.
Published: March 2017

In this collection of points following the discussion of Congress papers by Winnicott and Greenacre on the parent-infant relationship, Winnicott states that he has learnt from the discussion, in particular from Greenacre’s discussion of aggression. He finds that there is a positive effect of understanding the whole infant-mother relationship as a real and rich experience. He refers to Balint on language, to the subject of predestination raised by Lagache, to Klein on envy, and to Martin James on the false self, quoting Hamlet’s line that Osric ‘did comply with his dug before he sucked it’. He argues finally that abnormalities in the mother-baby relationship can develop very early, noting that this demonstrates that the subject of infancy can be extremely fruitful for psychoanalytic discussion.