The identification of Smad proteins as molecular components of the transforming growth factor-β (TGF-β) signaling cascade has enhanced our understanding of how ligand-mediated activation of TGF-β receptors leads to modulation of target gene transcription. Recent studies have identified a distinct, structurally related class of Smads which inhibits, rather than transduces, TGF-β family signals. The molecular mechanism of action and the exact signaling pathways that are targeted by antagonistic Smads are not completely understood. These proteins appear to participate in autoregulatory negative (...) feedback loops in which signaling initiated by specific TGF-β family ligands induces the expression of an inhibitory Smad that then functions to modulate the amplitude or duration of signaling. Negative feedback circuits such as these play important roles in fine-tuning the activity of multifunctional signaling molecules during embryonic patterning and in response to pathologic stimuli in adults. BioEssays 21:382–390, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

This article analyses domestic and foreign reactions to a 2008 report in the British Medical Journal on the complementary and, as argued, synergistic relationship between palliative care and euthanasia in Belgium. The earliest initiators of palliative care in Belgium in the late 1970s held the view that access to proper palliative care was a precondition for euthanasia to be acceptable and that euthanasia and palliative care could, and should, develop together. Advocates of euthanasia including author Jan Bernheim, independent from but (...) together with British expatriates, were among the founders of what was probably the first palliative care service in Europe outside of the United Kingdom. In what has become known as the Belgian model of integral end-of-life care, euthanasia is an available option, also at the end of a palliative care pathway. This approach became the majority view among the wider Belgian public, palliative care workers, other health professionals, and legislators. The legal regulation of euthanasia in 2002 was preceded and followed by a considerable expansion of palliative care services. It is argued that this synergistic development was made possible by public confidence in the health care system and widespread progressive social attitudes that gave rise to a high level of community support for both palliative care and euthanasia. The Belgian model of so-called integral end-of-life care is continuing to evolve, with constant scrutiny of practice and improvements to procedures. It still exhibits several imperfections, for which some solutions are being developed. This article analyses this model by way of answers to a series of questions posed by Journal of Bioethical Inquiry consulting editor Michael Ashby to the Belgian authors. (shrink)

Medical, scientific and societal progress has been such that, in a universalist humanist perspective such as the WHO’s, it has become an ethical imperative for the primary endpoints in evidence based health care research to be expressed in e.g. Quality Adjusted Life Years (QALYs). The classical endpoints of discrete health‐related functions and duration of survival are increasingly perceived as unacceptably reductionistic. The major problem in ‘felicitometrics’ is the measurement of the ‘quality’ term in QALYs. That the mental, physical and social (...) domains, each containing many dimensions and items, all contribute to QOL is uncontroversial. What is controversial, is the weight of the different dimensions in overall QOL. It has been shown to be very different between different patient populations. In human individuals, assuredly complex systems, the many dimensions and items of QOL observably interact, probably sometimes also in chaotic ways. In these conditions, the weights of isolated items in individuals become for all practical purposes meaningless. Therefore, the much used multi‐item questionnaires at best describe, but do not evaluate QOL, neither in individuals, nor in populations. For example, allergic patients treated with cetirizine scored better than those a placebo on all dimensions of the SF‐36, a standard QOL questionnaire. Here there is no serious doubt that the treatment improved QOL, because it is highly unlikely that any important dimension on which the patient groups would have scored otherwise is missing in the SF‐36. However, whether piracetam treatment of acute stroke, which improved the surrogate endpoints neurological and functional scores, also improved QOL is plausible, but will be proven only when comprehensive QOL measurement will have been done. And suppose in randomised populations of end‐stage metastatic solid cancer patients, one would compare palliative last‐line chemotherapy with only palliative care, and one would, as can be expected, find no significant differences in average survival, and chemotherapy superior for the mental domain, but inferior for the physical comfort domain: we would not know which treatment, on aggregate, would be the better. The problem is that QOL is an individual and emergent construct, the resultant of a great many intractions, and of a different order than its contributing components. Overall QOL can therefore best be captured only as the Gestalt of a global self‐assessment. Just as people in everyday life, while acting under uncertainty, make global assessments all the time, so they can seriously answer the serious question: ‘How have you been?’ A solemn, practical, non peer‐relativistic, non‐cultural, experiential, and well tolerated way to obtain such responses is Anamnestic Comparative Self Assessment (ACSA), in which the subjects' memories of the best and the worst times in their life experience define their individual scale of QOL. ACSA is thus both exquisitely idiosyncratic, and yet can in a universalist humanistic perspective be considered generic. Using both a multi‐item questionnaire and a global assessment allows by one logistic regression, to estimate the weights of the dimensions and items in populations, and thus identify those whose improvement would most contribute to the QOL of the greatest number. A combined approach to measurement of QOL is necessary to maximise the utility of QOL interventions. (shrink)

Recently, heated discussions about artificial intelligence, creativity, and work have re-emerged. Despite the dominant focus on the novelty of this entanglement, it is rich with history. In this paper, I will first introduce creativity as a historical and socio-culturally embedded concept, looking at how and why we have invented creativity in the guises we have. The focus will mostly be on the political and ideological backdrop of these historical processes–for instance how creativity was repeatedly cast as the positive counterimage of (...) (industrial and bureaucratic) alienated labour, and hence stood in a complex relationship to automation, robotization, and so on. Based on this I will then discuss a series of scenarios that are related to the (perhaps) forthcoming automation of creativity, more specifically four ways in which automation might in different ways impact (the fields of) creative practices and labour. (shrink)

The use of quality of life (QOL) outcomes in clinical trials is increasing as a number of practical, ethical, methodological, and regulatory reasons for their use have become apparent. It is important, then, that QOL measurements and differences between QOL scores be readily interpretable. We study interpretation in two contexts: when determining QOL and when basing decisions on QOL differences. We consider both clinical situations involving individual patients and research contexts, e.g., randomized clinical trials, involving groups of patients. We note (...) the ethical importance of such understanding: proper interpretation and communication facilitate health care decision making. Communication that facilitates interpretation is of moral significance since better communication can attenuate ethical problems and inform choices. Much of what is communication worthy about QOL assessments is determined by the particular QOL instrument used in the assessment and how it is administered. In practice, these choices will be driven by the purpose of the assessment, but, it is argued, to maximize understanding, we should combine the information garnered from traditional standardized QOL instruments, from individualized QOL assessments, and from a recently proposed dialogic paradigm, where QOL is determined by shared conversation regarding the interpretation of texts. And, while some studies can surely succeed using abbreviated methods of administration (e.g., postal surveys may suffice for certain purposes), we will focus on methods of administration involving interviewer–respondent interaction. We suggest that during the QOL elicitation process, interviewer and respondent should engage in a two-way conversation in order to achieve a shared understanding of the “answers” to QOL “questions” and, finally, to reach a shared interpretation of the individual’s QOL. (shrink)

Data Safety and Monitoring Boards were introduced in the 1960s to monitor data in clinical trials to ensure subject safety. It was thought important that DSMB members be experts in the field of interest, but not otherwise involved in the study in order to maximize objectivity. Since then, the use of DSMBs has increased dramatically, and their scope has expanded to include scientific issues — in particular, to avoid bias that can result when trials are stopped early because of evidence (...) that one treatment has greater efficacy or causes greater harm than another; or that no treatment is likely to do better than any other. (shrink)

During the 1980s many communities turned to grassroots activities to promote economic development, rather than relying on industrial recruitment strategies. We evaluate the characteristics of these projects, their benefits and costs, and obstacles they face in the development process. The data are drawn from a survey of more than one hundred communities in the United States. Self-development efforts do not appear to replace traditional rural economic development activities, but may complement them. Self-development activities produce a wide variety of jobs that (...) are taken primarily by local residents. The cost and availability of credit are major obstacles for self-development projects. Although self-development strategies should not be considered the primary economic development strategy for most rural communities, they do enable communities to build a more viable local economy. (shrink)

Introduction [Nancy L. Rosenblum] I. Varieties of Liberalism Today 1. The Liberalism of Fear [Judith N. Shklar] 2. Humanist Liberalism [Susan Moller Okin] 3. Liberal Democracy and the Costs of Consent [Benjamin R. Barber] II. Education and the Moral Life 4. Undemocratic Education [Amy Gutmann] 5. Civic Education in the Liberal State [William Galston] III. Moral Conflict 6. Class Conflict and Constitutionalism in J. S. Mill’s Thought [Richard Ashcraft] 7. Making Sense of Moral Conflict [Steven Lukes] 8. Liberal Dialogue (...) Versus a Critical Theory of Discursive Legitimation [Seyla Benhabib] IV. Repairing Individualist and Communitarian Failings 9. Cross-Purposes: The Liberal--Communitarian Debate [Charles Taylor] 10. Democratic Individuality and the Meaning of Rights [George Kateb] 11. Pluralism and Self-Defense [Nancy L. Rosenblum] 12. The Permanent Structure of Antiliberal Thought [Stephen Holmes]. (shrink)

How the new conspiracists are undermining democracy—and what can be done about it Conspiracy theories are as old as politics. But conspiracists today have introduced something new—conspiracy without theory. And the new conspiracism has moved from the fringes to the heart of government with the election of Donald Trump. In A Lot of People Are Saying, Russell Muirhead and Nancy Rosenblum show how the new conspiracism differs from classic conspiracy theory, why so few officials speak truth to conspiracy, and (...) what needs to be done to resist it. Classic conspiracy theory insists that things are not what they seem and gathers evidence—especially facts ominously withheld by official sources—to tease out secret machinations. The new conspiracism is different. There is no demand for evidence, no dots revealed to form a pattern, no close examination of shadowy plotters. Dispensing with the burden of explanation, the new conspiracism imposes its own reality through repetition and bare assertion. The new conspiracism targets democratic foundations—political parties and knowledge-producing institutions. It makes it more difficult to argue, persuade, negotiate, compromise, and even to disagree. Ultimately, it delegitimates democracy. Filled with vivid examples, A Lot of People Are Saying diagnoses a defining and disorienting feature of today's politics and offers a guide to responding to the threat. (shrink)

Rosenblum argues that we should judge associations not only by what they do for civic virtue, but also by what they do for individual members.

Elements of the relation between religion and politics are standard themes in political theory: toleration and free exercise rights; the parameters of separation of church and state; arguments for and against constraints imposed on religious discourse by philosophic norms of public reason. But religious parties and partisanship are no part of political theory, despite contemporary interest in value pluralism and in liberal democratic theory's capacity to address multicultural, religious, and ethnic group claims. This essay argues that religious parties are missing (...) elements in discussions of identity politics. They play an important role not just in expressing but also in constructing and mobilizing religious political identity. Political activity linked to parties is a principal way of bringing diffuse, politically unorganized groups, whose leaders are self-appointed and not regularly accountable for the way they represent co-religionists in political life, into the democratic mainstream. With political organization and especially partisanship, the fact of pluralism is made concrete for democratic purposes. (shrink)

How our everyday interactions as neighbors shape—and sometimes undermine—democracy "Love thy neighbor" is an impossible exhortation. Good neighbors greet us on the street and do small favors, but neighbors also startle us with sounds at night and unleash their demons on us, they monitor and reproach us, and betray us to authorities. The moral principles prescribed for friendship, civil society, and democratic public life apply imperfectly to life around home, where we interact day to day without the formal institutions, rules (...) of conduct, and means of enforcement that guide us in other settings. In Good Neighbors, Nancy Rosenblum explores how encounters among neighbors create a democracy of everyday life, which has been with us since the beginning of American history and is expressed in settler, immigrant, and suburban narratives and in novels, poetry, and popular culture. During disasters, like Hurricane Katrina, the democracy of everyday life is a resource for neighbors who improvise rescue and care. Degraded, this framework can give way to betrayal by neighbors, as faced by the Japanese Americans interned during World War II, or to terrible violence such as the lynching of African Americans. Under extreme conditions the barest act of neighborliness is a bulwark against total ethical breakdown. The elements of the democracy of everyday life—reciprocity, speaking out, and "live and let live"—comprise a democratic ideal not reducible to public principles of justice or civic virtue, but it is no less important. The democracy of everyday life, Rosenblum argues, is the deep substrate of democracy in America and can be its saving remnant. (shrink)

One under-theorized aspect of "multiculturalism and the antidiscrimination principle" is religious and ethnicity based political parties. With political organization, the fact of pluralism is made concrete for democratic purposes. When the struggle for empowerment is "waged within the world of democratic politics" it is waged through parties. That is the associational form modern democracies have settled on for participation, representation, and governing, and for countervailing power and regular opposition. Particularist parties and bloc voting are key instruments of political conflict and, (...) as important, of political integration. This Paper looks at the challenges these parties pose to democracy; specifically, at the principal reasons given for banning parties from participation in electoral politics. I identify four categories of justification for disqualification: violent overthrow, incitement to hate, altering the character of the nation, and outside support or control. This is a preliminary to setting out regulative principles of "defensive democracy.". (shrink)

These are the challenges taken up in Obligations of Citizenship and Demands of Faith, an exploration of the place of religion in contemporary public life.