bluuebunny/crossref_metadata_2025 huggingface dataset:
Remaking the British Atlantic
Authors: Marshall P. J.
Published: May 2012

How did Britain and America face up to the new world of American independence? This book argues that there was a sharp division between political relations and the many other links that had bound British and American people together before the Revolution. There was to be no political rapprochement. Peace was made in 1783, but it was not a peace of reconciliation. Mutual ill feeling remained. Americans continued to denounce what they saw as a corrupted British political system that had betrayed the historic liberties of the ancient British constitution, while British commentators dismissed American republicanism as the tyranny of the mob that undermined effective government. Resentment simmered on for many years' especially, on the American side, over the terms on which Anglo‐American trade was to be resumed, and, on the British side, over the failure of the Americans to pay off their debts. In spite of these disputes, Britons and Americans quickly began to cross the Atlantic again in large numbers, many British and especially Irish people migrated to settle in America and trade continued on a very large scale. Americans consumed British goods and read British books. Shared tastes and a common culture and values ensured that British influences would still be strong and that independent Americans would remain essentially British in outlook for a long time to come.
Introduction
Authors: Marshall Peter J.
Published: May 2012

After explaining how the book is divided into sections, one dealing with continuing political hostility and the other with the resumption of transatlantic links, which amounted to the restoration of a British Atlantic world, the Introduction sets the scene on the British side. It describes the attitudes during the war of those who had been hostile or friendly to the American cause. It shows how many who had supported the war were ultimately willing to accept that American independence would not necessarily do irrecoverable damage to British interests, although they still remained hostile to a new America after the war. This hostility was to be enduring, while wartime professions of friendship by those who had supported the American cause had little effect on post‐war British policies towards the United States.
5 The Politics of Trade
Authors: Marshall Peter J.
Published: May 2012

Commerce was the most contentious issue in Anglo‐American relations after the war. Americans regarded the development of a merchant marine and oceanic trade as essential elements of their independence. They hoped for a connection with Britain based on equality: Britain would have access to their market, while they would be able to trade freely throughout the British empire, especially with the West Indies. Britain hoped to recover American markets, but those who devised post‐war commercial policy were determined both to protect British shipping and to limit American maritime competition by excluding American ships from the West Indies and other British colonies. Negotiations with America for a commercial treaty were broken off. This situation was intensely resented in America. There were advocates in Britain of free trade with the Americans, but the exclusions remained the policy of the British government.
6 Imperial Frameworks
Authors: Marshall Peter J.
Published: May 2012

Failure in America raised questions about the value of colonies and the future of the British empire. British governments, however, considered that certain colonial possessions remained of fundamental importance and that they should continue to be managed on established principles. The prominence given to Ireland and the West Indies together with the remaining North American colonies meant that the Atlantic remained the main sphere of British concerns, although the East India Company's Indian territories was becoming a major imperial commitment which was gaining in consequence. The chapter stresses continuities rather than changes which might be seen as marking any immediate shift towards the creation of second empire different from that before the loss of America. A concluding section notes the beginnings of a new American continental empire purporting to be very different from the British one.
14 Customs in Common
Authors: Marshall Peter J.
Published: May 2012

Ardent republicans hoped that the American Revolution would not only lead to self‐government but to a revolution in ideas and manners that would make America independent of British influences. Americans and Britons had, however, too much in common for such a revolution to take quick effect. Both saw themselves as free people, whose rights were guaranteed by the English common law, which, suitably modified, Americans cherished as their own inheritance. Although often exhorted to, Americans were not prepared to renounce English fashions and models of genteel living. Most of the books they read were published in Britain. They sought recognition of their cultural and artistic achievements in Britain. Americans aspired to eminence in scientific learning, but here too they craved British recognition and created learned societies following British models.
15 Transatlantic Protestants
Authors: Marshall Peter J.
Published: May 2012

During the colonial period British Protestant denominations had established themselves in America. Right up to the Revolution most American Protestants kept close links with their colleagues in Britain, seeking financial and political support from them. Denominations were split by the war, although the established churches of England, outside the American south, and of Scotland tended to favour the British side and many Dissenters adhered to the American cause. Some American denominations were strengthened by the war while others lost ground. Independence brought about significant changes in relations between British and American Protestants. American denominations now generally ran their affairs without much reference to Britain, sometimes obtaining formal recognition of their autonomy. At the same time evangelical revivals were challenging denominations' authority and tending towards their fragmentation or the emergence of wholly new religious movements.
Conclusion
Authors: Marshall Peter J.
Published: May 2012

After a brief restatement of arguments about transatlantic political discord but continuing links in many other respects, the Conclusion goes on to consider the state of the British empire and the American union in the ten years or so after independence. It stresses the strength of ethnic, religious or regional loyalties and the difficulties facing both the British empire and the United States in commanding allegiance. The new America had an ambitious leadership but a population whose commitment to ideals of unity was uncertain. The subjects of the British empire were given to vigorous assertions of what they saw as their rights against imperial authority and were not likely to be enthusiastic adherents to doctrines of Britishness propagated from above. The book concludes that an Atlantic world that linked peoples survived the political developments that had divided them.
Heroic Homosociality and Homophobia in the Helgi Poems
Authors: Clark David
Published: May 2012

This chapter forms part of a pair with Chapter 1, and explores the Helgi poems's perspective on masculinity and homosociality through the character of Helgi Hundingsbani and his namesake Helgi Hjörvarðsson. It also introduces the work of another theoretician of gender and sexuality, Eve Kosofsky Sedgwick, as another way of bringing contemporary perspectives to bear into dialogue with medieval texts.
Kin-slaying in the Poetic Edda: The End of the World?
Authors: Clark David
Published: May 2012

Kin-slaying, and especially fratricide, constitute crucial factors in the history of both gods and men, recurring throughout the Codex Regius. This chapter's argument is that many events in the heroic poems, and in particular Hamðismál, function at least in part as microcosmic analogues of key events in the mythological texts, in particular Völuspá. The explicit references to Ragnarök in heroic poetry are explored, along with the links between the figures of Sigurðr and Baldr, and the way that human strife is thus linked to the archetypal cosmic strife.
Manslaughter and Misogyny: Women and Revenge in Sturlunga saga
Authors: Clark David
Published: May 2012

The final chapter returns to the issues of revenge and its relation to femininity with which we started in Chapter 1, but now in relation to the women of the contemporary sagas. It evaluates the contemporary saga writers’ attitudes to women and their perception of the role of women in the conflicts of the Sturlung Age. It shows that misogynistic tropes such as the scapegoating of women for the results of men's violent actions, and negative images possibly resting on religious constructions of women as irrational and corporeal, or even abject, are employed in Sturlunga saga. However, the picture is not a uniform one, and in several texts in the compilation one finds women acting as mediators or ‘anti-inciters’ who attempt to dissuade men from revenge and destructive acts.
Neuropathic pain
Authors: Moulin Dwight
Published: May 2012

This chapter illustrates with a case study the desired skills, attitudes, and expertise required to diagnose and manage neuropathic pain. It addresses several questions such as: What important features associated with neuropathic pain to look for on physical examination in this patient? What is neuropathic pain? What are the clinical features of neuropathic pain in this patient? What treatment to recommend for the patient?
Methadone and other novel treatments for pain
Authors: Hagen Neil , Ralph Christopher
Published: May 2012

This chapter presents a case study to show the necessary skills, attitudes, and background required to diagnose and manage cancer pain. It describes the use of three agents that have been employed in this setting — methadone, ketamine, and cannabinoids. It examines a number of questions such as: What is the pain diagnosis? What are the likely mechanisms of pain? How does methadone work as an analgesic? What are the main indications for the use of methadone? What are the reported mechanisms of analgesic effect of ketamine? What are the problems associated with the use of ketamine? What is the evidence that cannabinoids are useful for managing pain?
Anorexia–cachexia
Authors: MacDonald Neil
Published: May 2012

This chapter contains a case study to present the valuable skills, attitudes, and knowledge needed to diagnose and manage anorexia-cachexia. It addresses several questions such as: What are the definitions of anorexia and cachexia? What are the clinical characteristics of patients with anorexia-cachexia syndrome? Are some cancers more likely than others to cause cachexia? How does a chronic inflammatory state cause cachexia? What is the framework for your anorexia-cachexia therapeutic platform?
Palliative sedation
Authors: Pereira José , Gratton Valerie , Beauverd Michel
Published: May 2012

This chapter gives case studies which show the desired skills, attitudes, and expertise required for the practice of palliative sedation (PS). It puts forth several questions such as: What is PS? What are the prerequisites for initiating PS? How often is PS required in palliative care practice? What are the indications for using PS? Can PS therapy be misused? Why are clinical practice guidelines essential in the practice of PS? Is this euthanasia? What are the ethical considerations surrounding PS?
The last days
Authors: Henderson David , McIntyre Paul
Published: May 2012

This chapter presents a case study to illustrate the desired skills, attitudes, and knowledge required to integrate the needs of the dying patient and their family when providing care. It considers some questions such as: What is required to understand better and treat Mrs S. B. 's current situation (Mrs S. B. is a seventy-four-year-old woman with non-small-cell lung cancer and liver metastases). What possible reasons might there be for Mrs S. B.'s decline? What resources need to be in place to enable Mrs S. B. to remain at home for her last days and hours? How to assess the patient's and family's insight and understanding? What will dying look like? What needs to happen at the time of death?
Introduction
Authors: James Susan
Published: May 2012

The introduction sets out a distinctive methodological approach to the study of the Theologico‐Political Treatise. In contrast to the stances taken by many other commentators, this book illuminates the argument of the Treatise by setting it in the historical context of the political and theological debates of the Dutch Republic to which Spinoza is contributing. The work emerges as a highly critical intervention in a series of interconnected disputes. Spinoza aims to discredit a range of influential parties and redirect the course of power. At the same time, he attempts to analyse the conditions in which Dutch citizens can best progress towards the good life that he outlines in his Ethics. His argument is conducted on two levels, the philosophical and the imaginary, each of which has its own authority. To understand the Treatise, it is vital to be sensitive to these registers and to Spinoza's continual shifts from one to the other.
What Divine Law Is Not
Authors: James Susan
Published: May 2012

Spinoza's theological opponents agree that the core religious teaching of the Bible is the divine law revealed by the prophets, but disagree about the law's status and content. In order to show what is superstitious in their opinions, Spinoza must confront these disputes. His first step is to establish that the divine law is universal. The claim that the law was ordained for the Jews, as the Old Testament seems to claim, thus rests on a misinterpretation. This chapter examines Spinoza's philosophical argument for this conclusion. It shows how his view threatens Calvinist providentialism, and constitutes an attack on two flourishing seventeenth‐century movements, Christian millenarianism and Jewish Messianism. The argument is therefore not merely about the proper interpretation of the Bible. It is also a theologico‐political intervention in Dutch affairs.
What Divine Law Is
Authors: James Susan
Published: May 2012

Spinoza's positive account of the divine law is an extremely radical one, almost uniquely so in the context of seventeenth‐century debate. God is not a legislator who issues decrees and punishments, and prescriptions only become laws when they are ordained by a human agent. Human beings must therefore take responsibility for the laws under which they live. This chapter analyses Spinoza's complex defence of this position, tracing his distinctions between divine law, divine natural law, and revealed law. It also explains how the Treatise employs these resources to defend a number of controversial claims. Some of these are positive—for example, philosophy rather than Scripture yields the clearest understanding of what divine law prescribes. Many of them are negative—for example, Spinoza's account of law is designed to undermine the providentialism around which Calvinist theology is organized. Here we see Spinoza articulating the practical implications of his own philosophy.
Life in a Republic: The Lessons of Philosophy
Authors: James Susan
Published: May 2012

Living a religious life of the kind Spinoza has described is a theologico‐political enterprise, and depends on the existence of some sort of political community. Focusing on republics, the Treatise asks how this kind of state can best create secure and peaceful conditions in which individuals can live religiously and philosophise freely. Spinoza's discussion begins with an idealized, philosophical account of the process by which rational individuals can freely submit to a sovereign, this forming a state. While he draws heavily on the views of Hobbes, this chapter explores his distinctive treatment of the right of nature, the social contract and sovereign power. Political power or right, as Spinoza envisages it, consists in a balance of the powers held by the sovereign and its subjects, each of which is dependent on the other, and each of which is sustained by fictional narratives such as the story of a social contract.
Sovereignty and Freedom
Authors: James Susan
Published: May 2012

Along with many other Dutch republican writers, Spinoza holds that the sovereign must control sacred as well as civil matters, although in doing so he challenges the Dutch Reformed Church. Drawing on the example of the Hebrew Republic, he advocates the unification of civil and religious law. This suggestion guides an argument to the effect that piety (the goal of true religion and thus divine law) is a condition of peace (the goal of civil law) and vice versa, so that sovereign and citizens must protect both values, together with the religious pluralism and freedom to philosophize on which they depend. How far, exactly, should religious freedom and the freedom to philosophize extend? Spinoza sets out some limits. Nevertheless, republics become more secure as they cultivate a democratic ethos, and develop resources for engaging in the kind of peaceful debate that is the hallmark of genuine philosophy.
Moving beyond the Crisis: Tax Policies for the Soundness of Financial Markets
Authors: Lloyd Geoff
Published: May 2012

Systemic tax biases in favour of corporate debt financing and investment returns in the form of capital gains may have strengthened non-tax incentives to greater leverage, greater risk taking, and a lack of transparency, which were among the root causes of the financial crisis. Such tax biases were in each case exacerbated by increased tax arbitrage activity, tax-driven structured finance, and use of tax havens, facilitated by globalization and financial innovation. While this activity may in part have disappeared as a result of the significant losses incurred by financial institutions, other tax-related asymmetries may come to dominate behaviour in coming years. As part of an overall strategic response to the financial crisis, there is a case for identifying well-targeted reforms that might reduce or remove the incentives to financial instability caused inadvertently by common features of national tax systems. An appendix discusses the tax implications of financial institutions’ losses.
The End of the End of Ideology
Authors: Jost John T.
Published: May 2012

The “end of ideology” was declared by social scientists in the aftermath of World War II. They argued that ordinary citizens lack meaningful, coherent political attitudes that could be classified as “liberal” (or leftist) or “conservative” (or rightist). The end-of-ideologists were so influential that researchers ignored the topic of ideology for many years. However, current political realities, recent data from the American National Election Studies, and results from an emerging psychological paradigm provide strong grounds for returning to the study of ideology. Studies reveal that there are indeed meaningful political and psychological differences that covary with ideological self-placement. Situational variables—including system threat and mortality salience—and dispositional variables—including openness and conscientiousness—affect the degree to which an individual is drawn to liberal versus conservative leaders, parties, and opinions. A psychological analysis is also useful for understanding the political divide between “red states” and “blue states.”
The Policy IAT
Authors: Hanson Jon , Yeboah Mark
Published: May 2012

Since its initial publication, the Implicit Association Test (IAT) has been applied in a diverse array of disciplines. Application to the legal and policy arenas, however, has been uncommon. This is true even though the dominant schemas that shape law and policy are like the attitudes, stereotypes, and other forms of implicit cognition that the IAT is so often harnessed to measure. Based upon research designed to identify the dominant knowledge structures, schemas and categories that shape law and policy, the most significant and salient policy scripts boil down to "markets are good, regulation is bad." This chapter will discuss the initial results of an ongoing Policy IAT intended to investigate the strength of those policy scripts across the ideological spectrum. The results shed light on the variability of policy scripts across political categories and attributional styles along a situationist-dispositionist spectrum as well as the malleability of implicit associations.
Identity, Belief, and Bias
Authors: Cohen Geoffrey L.
Published: May 2012

This chapter presents research on the social psychology of identity and belief. Beliefs tied to long-held identities resist change and bias the processing of new information. Theoe phenomena help explain defensive denigration of victims of social problems, resistance to persuasion, intransigence in negotiation, and discrimination in hiring decisions. In each case, intervention strategies based on a social-psychological analysis provide a potential remedy.
Backlash: The Reaction to Mind Sciences in Legal Academia
Authors: Benforado Adam , Hanson Jon
Published: May 2012

This chapter demonstrates that naive cynicism is a pervasive dynamic that shapes policy debates big and small. It argues that naïve cynicism can operate at a particular moment or over long periods of time, and that naïve cynicism is embraced and encouraged by both elite knowledge-producers and the average person on the street. Examining the reactions of prominent academics to situationist scholarship, the chapter offers evidence that naive cynicism has played a significant role in retarding the growth and influence of insights drawn from social psychology and related fields within the dominant legal theoretical frameworks of the last half-century. Despite providing a more accurate depiction of the behavior of legal actors, this research from the mind sciences has been dismissed for decades in favor of commonsense dispositionist notions of causation, responsibility, and blame.
The Mystique of Instrumentalism
Authors: Tyler Tom , Rankin Lindsay
Published: May 2012

Ideology includes a set of shared assumptions about “truths” which are widely perceived as self-evident. This chapter focuses upon a set of truths concerning human nature in relationship to the law and legal authority. Those truths are united by their exaggerated belief in the effectiveness of instrumental approaches to people. An instrumental approach is one that seeks to shape behavior by either providing people with incentives or threatening to (or actually) punishing them. In law, the focus is on the efficacy of threatening to (or actually) punishing people for rule breaking behavior. This chapter argues for several basic propositions. First, people within our society share the belief that instrumental mechanisms are effective ways of motivating people—that punishment “works.” Second, empirical evidence consistently contradicts that belief. Third, there are alternative approaches that work better. Finally, the persistence of flawed beliefs despite contradictory evidence suggests that these beliefs are part of a culturally transmitted and supported ideology. This chapter concludes by discussing some of the reasons that this ideology persists.
Legal Interpretation and Intuitions of Public Policy
Authors: Furgeson Joshua , Babcock Linda
Published: May 2012

Studies of actual judicial decisions and recent experimental work simulating legal decision-making reveal a strong relationship between ideology and judicial decisions. There is also preliminary evidence linking ideology and constitutional interpretation preferences. This chapter proposes that legal decisions’ policy implications generate an automatic, affective response that biases subsequent information processing. The biased processing can involve: positive-testing or searching mostly for information supporting initial beliefs; counter-arguing or more critically scrutinizing information inconsistent with goals; overweighting information consistent with goals and discounting inconsistent information; and biases in storing and retrieving information. This motivated reasoning is more likely to influence decisions when the legal evidence is more ambiguous. As ideology operates through non-conscious cognitive processes, judges cannot identify ideology’s impact, making debiasing difficult.
Depoliticizing Administrative Law
Authors: Sunstein Cass R. , Miles Thomas J.
Published: May 2012

A large body of empirical evidence demonstrates that judicial review of agency action is highly politicized in both the federal courts of appeals and the Supreme Court. These results hold for both (a) judicial review of agency interpretations of law and (b) judicial review of agency decisions for “arbitrariness” on questions of policy and fact. The empirical results raise an obvious question: what might be done to depoliticize administrative law? Three sets of imaginable solutions have promise: (1) self-correction without formal doctrinal change, produced by a form of “debiasing” that might follow from a clearer judicial understanding of the current situation; (2) doctrinal innovations, as, for example, through rethinking existing deference principles and giving agencies more room to maneuver; and (3) institutional change, through novel voting rules and requirements of mixed panels. An investigation of these solutions has implications for other domains in which judges are divided along political lines, and indeed in which nonjudicial officials show some kind of politicized division or bias.
How we Grow Unequal
Authors: Emmenegger Patrick , Häusermann Silja , Palier Bruno , Seeleib-Kaiser Martin
Published: May 2012

This chapter introduces the concept of dualization. Poverty, inequality, and social exclusion are back on the political agenda in many rich democracies of Western Europe and North America, not only as a consequence of the Great Recession that hit the global economy in 2008. It argues that the translation of structural pressures into policies and outcomes has to be understood as a political process. Dualization is a political process that is characterized by the differential treatment of insiders and outsiders and that can take the form of newly created institutional dualisms or the deepening of existing institutional dualisms (policy output). Thereby, changes in the labor market are translated into the social policy realm, where new distinctions arise or old institutional distinctions are re-activated. Feedback effects and vicious circles are likely to strengthen this effect because weak labor attachment and social exclusion are associated with weaker political representation.
How Rich Countries Cope with Deindustrialization
Authors: Emmenegger Patrick , Häusermann Silja , Palier Bruno , Seeleib-Kaiser Martin
Published: May 2012

This conclusive chapter reviews the comparative evidence accumulated throughout the book on the new, widening and deepening divides between insiders and outsiders. It answers two key questions: who are the outsiders? And what is driving dualization? Most importantly, the comparative evidence discussed in this chapter points to the crucial importance of political choice in shaping the social outcomes of deindustrialization. Hence, insider-outsider divides are not a straightforward consequence of deindustrialization, but rather the result of policy. Finally, the chapter speculates about the future development of dualized societies: are they on a road to ever more inequality and social exclusion, or can we expect new equilibria to last? It argues that several mechanisms - including institutional feedback, the occupational segmentation of labor markets and the weak political mobilization of outsiders – may stabilize the new inequalities brought about by dualization.
Religious Freedom, Democracy, and International Human Rights
Authors: Witte John , Green M. Christian
Published: May 2012

This chapter addresses questions concerning religious freedom, democracy, and human rights in international law. It discusses three particularly controversial issues that have become the focus of international attention and international law: proselytism (or evangelization in Christian terms); conversion (especially when conceived as apostasy); and blasphemy (recent reconceived as “defamation of religions”). Each of these three issues are among the most hotly contested religious freedom issues today, and arise particularly when religious traditions and religious believers confront each other in the current global resurgence of religion.
Where Is the Religion?
Authors: Barnett Michael
Published: May 2012

This chapter uses humanitarianism's androgynous quality—its possession of both religious and secular attributes—to explore two issues regarding the contemporary world order. First, the distinction between the religious and the secular is more deceptive than informative. Second, contemporary Western religious tradition and humanitarianism are equally wary of the “political.” The shifting terrain between religion and secularism within humanitarianism, and the political and the religious in humanitarianism, points to a faith-based world order.
Religion and Development
Authors: Marshall Katherine
Published: May 2012

This chapter argues that while the links between both ideas and practice that touch on religion and development are legion, an exploration of what that really means, intellectually and in practice, is still tentative and quite fragmented. The limitations in systematic investigation of the topic have several explanations. A prime reason is the breadth and complexity of the institutions and issues involved. Special sensitivities around the religion development nexus is another. Perhaps most significant is the historically shaped segmentation of language, relationships, and perspectives among different types of institutions. Despite much overlap and many synergies, the two worlds (development and faith) have largely operated in separate universes, with different institutional, intellectual, and ideological frames. The resulting disconnects and frictions can result in wasted resources and in the kind of tensions that sap will and operational efficiency. They dampen the potential energy and ingenuity that can come from creative partnerships among these different institutions. They matter above all because they represent missed opportunities in the global effort to confront the challenges of global poverty and inequity.
Interreligious Dialogue and International Relations
Authors: Banchoff Thomas
Published: May 2012

In September 2006 a retired German professor was invited back to Regensburg University to address his former colleagues. His presentation, entitled “Faith, Reason, and the University: Memories and Reflections,” explored the relationship between religion and philosophy in an extended academic manner. His erudition, interspersed with reminiscences, delighted his audience. But his words reverberated far beyond the lecture hall. The retired professor was Pope Benedict XVI, and his lecture included unflattering references to the Prophet Mohammed and Islam. Condemnations and protests erupted within the Muslim world. Benedict's Regensburg address and its aftermath pose the question of how interreligious dialogue relates to international relations. This chapter explores both the impact of interreligious dialogue on international relations, and vice-versa. It then returns to the Regensburg controversy as an illustration of both.
Islam and the Promenades of Global Media
Authors: Boroujerdi Mehrzad , Allem Nichole J.
Published: May 2012

This chapter addresses the following questions: Are new media strengthening a global Muslim identity? Or are they putting theology and jurisprudence deeper into the bounds of politics and the chaos of skepticism? Should Muslims have a dystopian vision of new media as a site of debauchery, or an optimistic view of media as the protagonist of a new type of esprit de corps? In recent times, the body of work on Muslims and media seems to have moved beyond past scholarship that dissected the Western voyeuristic gaze cast on Muslims to begin to look at how Muslim actors and groups are using media to achieve their own interests in a globalized economy transformed by communications technology. The vista is decidedly mixed. While savvy Muslim cybernauts have initiated an exciting voyage of discovery and expression, the more numerous members of the religious chattering class live confidently in their own information ghetto.
ACUTE EXUDATIVE POLYMORPHOUS VITELLIFORM MACULOPATHY IN A YOUNG WOMAN
Authors: Wiklund Anna , Peebo Beatrice B.
Published: May 2012

Purpose:

To describe ocular findings before and after the diagnosis of acute exudative polymorphous vitelliform maculopathy, in an otherwise healthy 28-year-old woman.

Methods:

Case report with 21-months of follow-up. Fundus photography, optical coherence tomography, fluorescein angiography, indocyanine green angiography, and autofluorescence were used for imaging the retina. To examine retinal function, full-field electroretinogram, multifocal electroretinogram, electrooculography, and dark adaptometry were performed. Genetic analysis for mutations associated with Best disease was done.

Results:

In the asymptomatic patient before diagnosis, white-yellow, drusen-like, subretinal depositions were found in both eyes. A few months later, the patient developed bilateral visual disturbances. Retinal examination at the acute phase revealed a characteristic pattern of multifocal white-yellow subretinal lesions in both posterior poles, imaged by ophthalmoscopy, fluorescein angiography, indocyanine green angiography, and optical coherence tomography. Additionally, electrooculography and dark adaptometry were abnormal. Full-field electroretinogram was normal, but multifocal electroretinogram revealed central depression of peak amplitudes. During the 21-month follow-up without any treatment, visual acuity recovered, electrooculography and dark adaptometry normalized, and the patient experienced one episode of relapse. Genetic studies excluded mutations in the bestrophin gene (BEST1).

Conclusion:

Acute exudative polymorphous vitelliform maculopathy is still a condition of unknown origin, primarily affecting the pigment epithelium. Earlier reports have discussed whether the condition is inherited or acquired. In this report, the presymptomatic retinal findings in acute exudative polymorphous vitelliform maculopathy are described for the first time, indicating that a condition may be associated with primarily affected retinal pigment epithelium.
RhoB regulates cell migration through altered focal adhesion dynamics
Authors: Vega Francisco M. , Colomba Audrey , Reymond Nicolas , Thomas Mairian , Ridley Anne J.
Published: May 2012

The Rho GTPase RhoB has been shown to affect cell migration, but how it does this is not clear. Here we show that cells depleted of RhoB by RNAi are rounded and have defects in Rac-mediated spreading and lamellipodium extension, although they have active membrane ruffling around the periphery. Depletion of the exchange factor GEF-H1 induces a similar phenotype. RhoB-depleted cells migrate faster, but less persistently in a chemotactic gradient, and frequently round up during migration. RhoB-depleted cells have similar numbers of focal adhesions to control cells during spreading and migration, but show more diffuse and patchy contact with the substratum. They have lower levels of surface β1 integrin, and β1 integrin activity is reduced in actin-rich protrusions. We propose that RhoB contributes to directional cell migration by regulating β1 integrin surface levels and activity, thereby stabilizing lamellipodial protrusions.
A doxycycline-dependent human immunodeficiency virus type 1 replicates in vivo without inducing CD4+ T-cell depletion
Authors: Legrand Nicolas , van der Velden Gisela J. , Fang Raphaël Ho Tsong , Douaisi Marc , Weijer Kees , Das Atze T. , Blom Bianca , Uittenbogaart Christel H. , Berkhout Ben , Centlivre Mireille
Published: May 2012

A novel genetic approach for the control of virus replication was used for the design of a conditionally replicating human immunodeficiency virus (HIV) variant, HIV-rtTA. HIV-rtTA gene expression and virus replication are strictly dependent on the presence of a non-toxic effector molecule, doxycycline (dox), and thus can be turned on and off at will in a graded and reversible manner. The in vivo replication capacity, pathogenicity and genetic stability of this HIV-rtTA variant were evaluated in a humanized mouse model of haematopoiesis that harbours lymphoid and myeloid components of the human immune system (HIS). Infection of dox-fed BALB Rag/γc HIS (BRG-HIS) mice with HIV-rtTA led to the establishment of a productive infection without CD4+ T-cell depletion. The virus did not show any sign of escape from dox control for up to 10 weeks after the onset of infection. No reversion towards a functional Tat–transactivating responsive (TAR) RNA element axis was observed, confirming the genetic stability of the HIV-rtTA variant in vivo. These results demonstrate the proof of concept that HIV-rtTA replicates efficiently in vivo. HIV-rtTA is a promising tool for fundamental research to study virus–host interactions in vivo in a controlled fashion.
The Vascular Pathogen Verticillium longisporum Requires a Jasmonic Acid-Independent COI1 Function in Roots to Elicit Disease Symptoms in Arabidopsis Shoots
Authors: Ralhan Anjali , Schöttle Sonja , Thurow Corinna , Iven Tim , Feussner Ivo , Polle Andrea , Gatz Christiane
Published: May 2012

Verticillium longisporum is a soil-borne vascular pathogen that causes reduced shoot growth and early senescence in Arabidopsis (Arabidopsis thaliana). Here, we report that these disease symptoms are less pronounced in plants that lack the receptor of the plant defense hormone jasmonic acid (JA), CORONATINE INSENSITIVE1 (COI1). Initial colonization of the roots was comparable in wild-type and coi1 plants, and fungal DNA accumulated to almost similar levels in petioles of wild-type and coi1 plants at 10 d post infection. Completion of the fungal life cycle was impaired in coi1, as indicated by the reduced number of plants with microsclerotia, which are detected on dead plant material at late stages of the disease. Contrary to the expectation that the hormone receptor mutant coi1 should display the same phenotype as the corresponding hormone biosynthesis mutant delayed dehiscence2 (dde2), dde2 plants developed wild-type-like disease symptoms. Marker genes of the JA and the JA/ethylene defense pathway were induced in petioles of wild-type plants but not in petioles of dde2 plants, indicating that fungal compounds that would activate the known COI1-dependent signal transduction chain were absent. Grafting experiments revealed that the susceptibility-enhancing COI1 function acts in the roots. Moreover, we show that the coi1-mediated tolerance is not due to the hyperactivation of the salicylic acid pathway. Together, our results have unraveled a novel COI1 function in the roots that acts independently from JA-isoleucine or any JA-isoleucine mimic. This COI1 activity is required for a yet unknown root-to-shoot signaling process that enables V. longisporum to elicit disease symptoms in Arabidopsis.
Rapid T cell repopulation after rabbit anti-thymocyte globulin (rATG) treatment is driven mainly by cytomegalovirus
Authors: Havenith S H C , Remmerswaal E B M , Bemelman F J , Yong S L , van Donselaar- van der Pant K A M I , van Lier R A W , ten Berge I J M
Published: May 2012

Rabbit anti-thymocyte globulin (rATG) induces a long-lasting lymphocytopenia. CD4+ T cells remain depleted for up to 2 years, whereas the CD8+ T cell compartment is refilled rapidly by highly differentiated CD27–CD45RA+CD57+effector-type cells. Because the presence of these highly differentiated CD8+ T cells has been associated with cytomegalovirus (CMV) infection, we questioned to what extent restoration of CMV T cell immunity contributes to the re-emergence of T cells following rATG treatment. We compared T cell repopulation in six CMV-seropositive patients with CMV reactivation (reactivating CMV+) to that in three CMV+ patients without reactivation (non-reactivating CMV+), and to that in three CMV-seronegative recipients receiving a kidney from a CMV-seronegative donor (CMV−/−). All patients received rATG because of acute allograft rejection. Total CD4 and CD8 counts, frequency and phenotype of virus-specific CD8+ T cells were determined. In reactivating CMV+ patients, total CD8+ T cells reappeared rapidly, whereas in non-reactivating CMV+ patients they lagged behind. In CMV−/− patients, CD8+ T cell counts had not yet reached pretransplant levels after 2 years. CMV reactivation was indeed followed by a progressive accumulation of CMV-specific CD8+ T cells. During lymphocytopenia following rATG treatment, serum interleukin (IL)-7 levels were elevated. Although this was most prominent in the CMV-seronegative patients, it did not result in an advantage in T cell repopulation in these patients. Repopulated CD8+ T cells showed increased skewing in their Vβ repertoire in both CMV−/− and reactivating CMV-seropositive patients. We conclude that rapid T cell repopulation following rATG treatment is driven mainly by CMV.
Role of intercellular adhesion molecule‐2 in osteoclastogenesis
Authors: Li Xianglan , Akiyama Masako , Nakahama Ken‐ichi , Koshiishi Taro , Takeda Satoru , Morita Ikuo
Published: May 2012

Osteoclasts, multinucleated bone‐resorbing cells, are specialized cells derived from the monocyte/macrophage lineage. Therefore, it is essential for mononuclear precursors to find a fusion partner during its differentiation. Our previous study showed an important role of cell communication via Mac‐1 (CD11b/CD18) during osteoclastogenesis. However, the counter receptor of Mac‐1 was still unknown. Flow cytometric analysis showed that bone marrow‐derived mononuclear cells, used as osteoclast precursors, expressed intercellular adhesion molecule‐1 and ‐2. Quantitative RT‐PCR analysis revealed that expression level of ICAM‐2 was higher than that of ICAM‐1 in bone marrow cells. The osteoclastogenesis induced by receptor activator of NF‐kappaB ligand (RANKL) was inhibited by anti‐ICAM‐2 neutralizing antibody but not by anti‐ICAM‐1 neutralizing antibody. The inhibitory effect of anti‐ICAM‐2 antibody on osteoclastogenesis was enhanced by simultaneous treatment of anti‐CD11b neutralizing antibody. Furthermore, osteoclastogenesis induced by tumor necrosis factor α (TNFα) was also inhibited by anti‐ICAM‐2 neutralizing antibody. The involvement of lymphocytes in osteoclastogenesis was excluded, because anti‐ICAM‐2 antibody inhibited osteoclastogenesis using bone marrow‐derived cells from immunodeficiency mice. Immunocytochemical staining demonstrated colocalization of ICAM‐2 and Mac‐1 during osteoclastogenesis; however, Mac‐1 immunoreactivity was lost in differentiated multinucleated osteoclast. These results suggest the important role of ICAM‐2/Mac‐1 binding in osteoclastogenesis induced by either RANKL or TNFα.
Kinetics of the interaction between anti‐FVIII antibodies and FVIII from therapeutic concentrates, with and without von Willebrand factor, assessed by surface plasmon resonance
Authors: Grancha S. , Ortiz A. M. , Marañón C. , Hampel K. , Moret A. , Zimmermann B. , Jorquera J. I. , Aznar J. A.
Published: May 2012

The presence of VWF in plasma‐derived FVIII (pdFVIII/VWF) products has been pointed out as a key difference with recombinant FVIII (rFVIII) products with regard to immunogenicity. A Surface Plasmon Resonance (SPR) study was designed to characterize in detail the interaction between anti‐FVIII (IgGs) from a severe haemophilia A patient, and FVIII from concentrates of different sources. Full‐length rFVIII (preincubated or not with purified VWF), B domain‐deleted (BDD)‐rFVIII and pdFVIII/VWF were analysed. To ensure reproducible conditions for accurate determination of kinetic constants, a capture‐based assay format was developed using protein G surfaces for specific and reversible coupling of endogenous anti‐FVIII antibodies. Concentration ranges (nm) of FVIII products tested were 9–0.03 (rFVIII) and 6–0.024 (pdFVIII/VWF). The association with antibodies was monitored for 3–5 min, whereas dissociation of the complex was followed for 5–20–240 min. A strong interaction of rFVIII and BDD‐rFVIII with patient's IgG was detected with the K
D values in the low picomolar range (5.9 ± 3.0 and 12.7 ± 6.9 pm, respectively) and very slow dissociation rates, while pdFVIII/VWF showed only marginal binding signals. The VWF complexed rFVIII displayed reduced binding signals compared with uncomplexed rFVIII, but the K
D was still in the picomolar range (4.1 ± 1.9 pm) indicating insufficient complex formation. rFVIII, alone or bound to exogenously added VWF, showed high affinity for anti‐FVIII IgGs from a severe haemophilia A patient whereas pdFVIII/VWF did not. These results are in agreement with those studies that point towards rFVIII concentrates to be more immunogenic than pdFVIII concentrates.
Large‐scale comparative analyses of immunomarkers for diagnostic subtyping of non‐small‐cell lung cancer biopsies
Authors: Warth Arne , Muley Thomas , Herpel Esther , Meister Michael , Herth Felix J F , Schirmacher Peter , Weichert Wilko , Hoffmann Hans , Schnabel Philipp A
Published: May 2012

Warth A, Muley T, Herpel E, Meister M, Herth F J F, Schirmacher P, Weichert W, Hoffmann H & Schnabel P A  (2012) Histopathology Large‐scale comparative analyses of immunomarkers for diagnostic subtyping of non‐small‐cell lung cancer biopsies

Aims:  Patient stratification according to histological subtype is important for non‐small‐cell lung cancer (NSCLC) therapy. For specimens with uncertain histomorphology, rational and material‐saving algorithms for specific and sensitive immunotyping need to be established.

Methods and results:  One thousand one hundred and forty‐five NSCLCs were immunohistochemically investigated for the expression of cytokeratin 5/6 (CK5/6), CK7, thyroid transcription factor‐1 (TTF‐1), p63, napsin‐A, and desmocollin‐3. Overall, napsin‐A and desmocollin‐3 were the most specific markers (specificity of each, 99%), and CK7 and CK5/6 the most sensitive markers (sensitivity, 96% and 94%) for adenocarcinomatous and squamous differentiation, respectively. However, for NSCLC not otherwise specified (NOS) cases, TTF‐1, p63, CK5/6 and CK7 were found to be the most reliable markers. On the basis of morphology alone, approximately two‐thirds of all NSCLCs could be reliably diagnosed in biopsy specimens. Immunohistochemistry further reduced the NOS fraction to 10%.

Conclusions:  When morphology alone is not reliable, the use of selected markers and marker panels is highly sensitive and specific, and allows reliable distinction between squamous cell carcinoma and adenocarcinoma. Considering the impact of typing for the selection of molecular testing and treatment response, one must be aware of immunomarker expression patterns in NSCLC and their diagnostic value, in order to optimize typing and thereby maximize patient benefit from chemotherapy.