Cascades of transcriptional regulation are the common source of the forward drive in all developmental systems. Increases in complexity and specificity of gene expression at successive stages are based on the collaboration of varied combinations of transcription factors already expressed in the cells to turn on new genes, and the logical relationships between the transcription factors acting and becoming newly expressed from stage to stage are best visualized as gene regulatory networks. However, gene regulatory networks used in different developmental contexts (...) underlie processes that actually operate through different sets of rules, which affect the kinetics, synchronicity, and logical properties of individual network nodes. Contrasting early embryonic development in flies and sea urchins with adult mammalian hematopoietic development from stem cells, major differences are seen in transcription factor dosage dependence, the silencing or damping impacts of repression, and the impact of cellular regulatory history on the parts of the genome that are accessible to transcription factor action in a given cell type. These different features not only affect the kinds of models that can illuminate developmental mechanisms in the respective biological systems, but also reflect the evolutionary needs of these biological systems to optimize different aspects of development. (shrink)

The vertebrate immune system provides a remarkable showcase of the different ways the genome can be used to specify cellular identity and to mediate cellular function. It is arguably the leading mammalian system in which gene regulation programs that drive the acquisition of specific cell-type identities have been elucidated at the single cell level. More broadly for molecular genomics, the activation-induced gene expression pathways used in immune effector responses have provided textbook cases for fundamental elements of transcription factor assembly at (...) enhancers ; and immune system genes and gene clusters have provided key paradigms for the roles of long-range.. (shrink)

The development of T cells and B cells from pluripotent hematopoietic precursors occurs through a stepwise narrowing of developmental potential that ends in lineage commitment. During this process, lineage-specific genes are activated asynchronously, and lineage-inappropriate genes, although initially expressed, are asynchronously turned off. These complex gene expression events are the outcome of the changes in expression of multiple transcription factors with partially overlapping roles in early lymphocyte and myeloid cell development. Key transcription factors promoting B-cell development and candidates for this (...) role in T-cell development are discussed in terms of their possible modes of action in fate determination. We discuss how a robust, stable, cell-type–specific gene expression pattern may be established in part by the interplay between endogenous transcription factors and signals transduced by cytokine receptors, and in part by the network of effects of particular transcription factors on each other. BioEssays 21:726–742, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

The European Union Commission’s whitepaper on Artificial Intelligence proposes shaping the emerging AI market so that it better reflects common European values. It is a master plan that builds upon the EU AI High-Level Expert Group guidelines. This article reviews the masterplan, from a culture cycle perspective, to reflect on its potential clashes with current societal, technical, and methodological constraints. We identify two main obstacles in the implementation of this plan: the lack of a coherent EU vision to drive future (...) decision-making processes at state and local levels and the lack of methods to support a sustainable diffusion of AI in our society. The lack of a coherent vision stems from not considering societal differences across the EU member states. We suggest that these differences may lead to a fractured market and an AI crisis in which different members of the EU will adopt nation-centric strategies to exploit AI, thus preventing the development of a frictionless market as envisaged by the EU. Moreover, the Commission aims at changing the AI development culture proposing a human-centred and safety-first perspective that is not supported by methodological advancements, thus taking the risks of unforeseen social and societal impacts of AI. We discuss potential societal, technical, and methodological gaps that should be filled to avoid the risks of developing AI systems at the expense of society. Our analysis results in the recommendation that the EU regulators and policymakers consider how to complement the EC programme with rules and compensatory mechanisms to avoid market fragmentation due to local and global ambitions. Moreover, regulators should go beyond the human-centred approach establishing a research agenda seeking answers to the technical and methodological open questions regarding the development and assessment of human-AI co-action aiming for a sustainable AI diffusion in the society. (shrink)

We are drowning in information, while starving for wisdom.Are the smartest people also the wisest? Not necessarily. While traditional intellectual reasoning and procedural knowledge have helped build the communities we live in, there is a growing scientific understanding that we need emotionally balanced and better-fitting prosocial frameworks for coping with the uncertainties and complexities of life and addressing new challenges of the modern world. We are now poised on the edge of a new science of wisdom.The concept of wisdom, long (...) considered the “pinnacle of insight into the human condition”, has been that of an intangible, subjective, culturally specific entity—an unscientific... (shrink)

This book discusses ways for people to handle today's bioethical issues in the context of America's history and culture--and from the perspective of various ...

While a significant literature has appeared discussing theoretical ethical concerns regarding COVID-19, particularly regarding resource prioritization, as well as a number of personal reflections on providing patient care during the early stages of the pandemic, systematic analysis of the actual ethical issues involving patient care during this time is limited. This single-center retrospective cohort mixed methods study of ethics consultations during the first surge of the COVID 19 pandemic in Massachusetts between March 15, 2020 through June 15, 2020 aim to (...) fill this gap. Results indicate that there was no significant difference in the median number of monthly consultation cases during the first COVID-19 surge compared to the same period the year prior and that the characteristics of the ethics consults during the COVID-19 surge and same period the year prior were also similar. Through inductive analysis, we identified four themes related to ethics consults during the first COVID-19 surge including (1) prognostic difficulty for COVID-19 positive patients, (2) challenges related to visitor restrictions, (3) end of life scenarios, and (4) family members who were also positive for COVID-19. Cases were complex and often aligned with multiple themes. These patient case-related sources of ethical issues were managed against the backdrop of intense systemic ethical issues and a near lockdown of daily life. Healthcare ethics consultants can learn from this experience to enhance training to be ready for future disasters. (shrink)

From February 2020, the COVID-19 pandemic led to closures of educational institutions to reduce the spread of infectious disease. This forced the U.S. education system into a massive experiment with online education. Despite conducting online bioethics education for nearly twenty years, our bioethics program, a joint endeavor of Clarkson University and Icahn School of Medicine at Mount Sinai, was not immune to this disruption because our curriculum features intensive, one-week onsite courses. Even in the face of historic disruptions, it is (...) vital to ensure minimal interruptions to teaching and assessing students to provide effective education. This paper reviews the steps we took to successfully convert the onsite components of our curriculum to a synchronous online format, and it focuses on how we preserved instruction and assessment of practical skills that comprise these courses’ core. It also explains how we fostered interactive classroom environments. (shrink)

Objective Although patients exercise greater autonomy than in the past, and shared decision making is promoted as the preferred model for doctor-patient engagement, tensions still exist in clinical practice about the primary locus of decision-making authority for complex, scarce, and resource-intensive medical therapies: patients and their surrogates, or physicians. We assessed physicians’ attitudes toward decisional authority for adult venoarterial extracorporeal membrane oxygenation (VA-ECMO), hypothesizing they would favor a medical locus. Design, Setting, Participants A survey of resident/fellow physicians and internal medicine (...) attendings at an academic medical center, May to August 2013. Measurements We used a 24-item, internet-based survey assessing physician-respondents’ demographic characteristics, knowledge, and attitudes regarding decisional authority for adult VA-ECMO. Qualitative narratives were also collected. Main Results A total of 179 physicians completed the survey (15 percent response rate); 48 percent attendings and 52 percent residents/ fellows. Only 32 percent of the respondents indicated that a surrogate’s consent should be required to discontinue VA-ECMO; 56 percent felt that physicians should have the right to discontinue VA-ECMO over a surrogate’s objection. Those who self-reported as “knowledgeable” about VA-ECMO, compared to those who did not, more frequently replied that there should not be presumed consent for VA-ECMO (47.6 percent versus 33.3 percent, p = 0.007), that physicians should have the right to discontinue VAECMO over a surrogate’s objection (76.2 percent versus 50 percent, p = 0.02) and that, given its cost, the use of VA-ECMO should be restricted (81.0 percent versus 54.4 percent, p = 0.005). Conclusions Surveyed physicians, especially those who self-reported as knowledgeable about VA-ECMO and/or were specialists in pulmonary/ critical care, favored a medical locus of decisional authority for VA-ECMO. VA-ECMO is complex, and the data may (1) reflect physicians’ hesitance to cede authority to presumably less knowledgeable patients and surrogates, (2) stem from a stewardship of resources perspective, and/or (3) point to practical efforts to avoid futility and utility disputes. Whether these results indicate a more widespread reversion to paternalism or a more circumscribed usurping of decisional authority occasioned by VA-ECMO necessitates further study. (shrink)

Wisdom is a multi-component trait that is important for mental health and well-being. In this study, we sought to understand gender differences in relative strengths in wisdom. A total of 659 individuals aged 27–103 years completed surveys including the 3-Dimensional Wisdom Scale and the San Diego Wisdom Scale. Analyses assessed gender differences in wisdom and gender’s moderating effect on the relationship between wisdom and associated constructs including depression, loneliness, well-being, optimism, and resilience. Women scored higher on average on the 3D-WS (...) but not on the SD-WISE. Women scored higher on compassion-related domains and on SD-WISE Self-Reflection. Men scored higher on cognitive-related domains and on SD-WISE Emotion Regulation. There was no impact of gender on the relationships between wisdom and associated constructs. Women and men have different relative strengths in wisdom, likely driven by sociocultural and biological factors. Tailoring wisdom interventions to individuals based on their profiles is an important next step. (shrink)

The Tennessee Supreme Court's decision in Davis v. Davis, a case that raises the question of how to allocate frozen embryos in the event of divorce, addresses many of the legal issues posed by in vitro fertilization. The decision considers the interests of the progenitors as well as of the children who may result. For example, the court held that gamete providers' discretion regarding the disposition of embryos can be limited only when their decisions would harm the children who might (...) be born. The court also made clear that efforts to seek genetic parenthood are protected only when accompanied by a desire to raise the resulting children, a conclusion that also affects other reproductive technologies. In addition to elaborating an analytic framework, the court set guidelines for resolving disputes when the couples had made no prior agreements, including holding that while the embryos are ex-utero the desire to avoid genetic parenthood almost always trumps the wish to become a parent. The well-reasoned analysis in Davis v. Davis should help shape legal and ethical discussion regarding the use of in vitro fertilization for many years to come. (shrink)

[v. 1] Thales to Democritus.--[v. 2] The Sophists. Socrates. Plato.--[v. 3] Aristotle.

Can the explanations which Freud gives of neurotic symptoms be seen as fitting into the pattern of rational explanation? After some clarification of the notion of a rational explanation, I shall be examining what I take to be the only plausible ways of trying to construe Freudian explanations as explanations of this type--by treating Freudian cases first as analogous to ordinary cases of pretending (Section II), secondly, as analogous to cases of superstitious belief (Section IV), and finally as analogous to (...) cases involving acts of communication (Section V). I shall be arguing that none of these ways of construing many of the Freudian explanations is successful. (shrink)

v. 1. Ancient and medieval.--v. 2. Modern.

The central goal of this essay is to develop a theory of justified paternalism that will be useful in evaluating and designing paternalistic public policies. The theory is designed for a society that promotes the development of characteristics of autonomy in its members. In the opening chapter I analyze widely-held legal, familial and philosophic conceptions of paternalism, discuss the inadequacies of each of those conceptions and develop a "unified" conception of paternalism. In Chapter II I analyze what it means to (...) be "morally responsible" and base this analysis on the legal, psychological and psychiatric accounts of responsibility that inform an autonomist society. From these analyses I develop two principles which inform an autonomist society: Respect for Others and Non-Interference and discuss the restraints on justifiable paternalism entailed by them. In Chapter III I discuss the roles of voluntariness and consent in the legal, phychiatric and philosophic concepts of moral responsibility and turn to an analysis of the disappointing treatments of these concepts in traditional philosophic justifications for paternalism. I argue that "unencumbered consent" is an appropriate concept of consent to utilize in any philosophic justification for paternalism that would be consistent with the concepts of moral responsibility and autonomy and the principles of respect for others and of non-interference. Chapter IV offers a decision-theoretic model justifying acting paternalistically for others. Each of the necessary conditions for justified paternalism is drawn from the aforementioned concepts and principles. In Chapter V, I show that if Rawls is to be consistent, he must adopt a theory of paternalism similar to mine, and I argue that my theory of paternalism overcomes libertarian, utilitarian and statistical arguments against it. I then apply the theory to specific forms of paternalism including involuntary commitment and guardianship, mandatory blood transfusions, flouridation of public water supplies, mandatory motorcycle helmets and seatbelts, social security taxation, mandatory education of children and suicide intervention. A 267-entry bibliography is appended. (shrink)

The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 19 (COVID-19) has led to the imposition of severely restrictive measures by governments in the Western hemisphere. We feel a contrast between these measures and our freedom. This contrast, we argue, is a false perception. It only appears to us because we look at the issue through our contemporary moral philosophy of utilitarianism and an understanding of freedom as absence of constraints. Both these views can be (...) substituted with more sophisticated alternatives, namely an ethics of virtue and a notion of freedom of the will. These offer a fuller picture of morality and enable us to cooperate with the current restrictions by consciously choosing to adhere to them instead of perceiving them as draconian and immoral. We ask whether we should collaborate with the restrictions and argue that considerations of virtue will lead to an affirmative answer. More broadly, virtue ethics permits to deal with the practical concerns about how an individual should behave during this pandemic, given the current lockdown measures or lack thereof. -/- In section 1, we present how utilitarianism and a notion of freedom as negative liberty support the opposition to restrictive measures. In section 2, we outline an alternative based on an ethics of virtue and a more elaborated notion of free will. In the concluding section 3, we argue that considerations of virtue should guide the individual and public response to the emergency. (shrink)

Medical assistance in dying legislation in Canada followed much deliberation after the Supreme Court of Canada’s ruling in Carter v. Canada. Included in this deliberation was the Special Joint Committee on Physician Assisted Dying’s recommendation to extend MAID legislation beyond the inclusion of adults to mature minors. Children's agency is a construct advanced within childhood studies literature which entails eliciting children’s voices in order to recognise children as active participants in constructing their own childhoods. Using this framework, we consider the (...) possible extension of MAID legislation to most minors. We highlight important questions regarding how insights from children’s voices could be mobilised in the life or death context of MAID. We conclude that children’s voices have the potential to help determine their eligibility for MAID; however, incorporating children's voices in the context of MAID requires careful consideration due to the complexity of voice. (shrink)

In Roman Catholic Political Philosophy author James V. Schall tries to demonstrate that Roman Catholicism and political philosophy—-revelation and reason—are not contradictory. It is his contention that political philosophy, the primary focus of the book, asks certain questions about human purpose and destiny that it cannot, by itself, answer. Revelation is the natural complement to these important questions about God, human being, and the world. Schall manages to avoid polemicism or triumphalism as he shows that revelation and political thought contribute (...) to a fuller understanding of each other. (shrink)

Writing in 1999, legal ethics scholar Brad Wendel noted that “[v]ery little empirical work has been done on the moral decision making of lawyers.” Indeed, since the mid-1990s, few empirical studies have attempted to explore how attorneys deliberate about ethical dilemmas they encounter in their practice. Moreover, while past research has explored some of the ethical issues confronting lawyers practicing in certain specific areas of practice, no published data exists probing the moral mind of health care lawyers. As signaled by (...) the creation of a regular column “devoted to ethical issues arising in the practice of health law” in the Journal of Law, Medicine & Ethics, the time to address the empirical gap in the professional ethics literature is now. Accordingly, this article presents data collected from 120 health care lawyers. Presenting this population with a number of hypothetical scenarios relating to how they would respond when confronting an ethical dilemma without an obvious solution or when facing a situation in which their personal values were in tension with their professional obligations, this article represents a first step toward better understanding how lawyers who practice in health care settings understand and resolve the moral discomfort they encounter in their professional lives. (shrink)

In Roman Catholic Political Philosophy author James V. Schall tries to demonstrate that Roman Catholicism and political philosophy—-revelation and reason—are not contradictory. It is his contention that political philosophy, the primary focus of the book, asks certain questions about human purpose and destiny that it cannot, by itself, answer. Revelation is the natural complement to these important questions about God, human being, and the world. Schall manages to avoid polemicism or triumphalism as he shows that revelation and political thought contribute (...) to a fuller understanding of each other. (shrink)

This essay fills in some historical, conceptual, and pedagogical gaps that appear in the most visible and recent professional efforts to “revive” Philosophy as a Way of Life (PWOL). I present “American Philosophy and Self-Culture” as an advanced undergraduate seminar that broadens who counts in and what counts as philosophy by immersing us in the lives, writings, and practices of seven representative U.S.-American philosophers of self-culture, community-building, and world-changing: Benjamin Franklin (1706–1790), Frederick Douglass (1818–1895), William Ellery Channing (1780–1842), Henry David (...) Thoreau (1817–1862), Margaret Fuller (1810-1850), Henry Bugbee (1915–1999), and Gloria Anzaldúa (1942–2004). Students enter the class with preconceptions about who philosophers are, what they do, how they write, and the languages in which they write. Students walk out with new senses of self, place, and language that emerge through new ways of seeing, doing, and writing philosophy. (shrink)

This paper aims to open up a problem for discussion and further research based on the three concepts of its title. It examines how these concepts are linked by a line of reasoning developed by the French philosopher, Louis Althusser. Althusser argues that liberal education is an ideological practice that serves to reproduce capitalist social formations. It directs people into preestablished, functional, class positions in society, yet it disguises this operation by keeping attention focused on the myth of our essential (...) subjectivity. This myth, which permeates the discourse of liberal education, is what constitutes humanism. In response to this skeptical view of liberal education and humanism, I start to develop Althusser’s formulations in a different direction. I argue that a humanism that takes fuller responsibility for theorizing the practice of liberal education may be able to revise that practice so that it serves socially transformative, rather than reproductive, ends. Such a humanism may be able to ground itself on an understanding of our subjectivity that emphasizes its reliance on a community of learning, one whose values intrinsically oppose those of capitalism. (shrink)

This paper examines the relationship between the public health community and the tobacco industry within the framework of a two-factor model of trust and distrust (Lewicki, McAllister & Bies, 1998). We assert that public health’s historical and current interaction with Big Tobacco is best characterized as one of Low Trust/High Distrust, marked by ongoing hostility and preemption. Forced-trust measures based on regulation and litigation and efforts by the tobacco industry to collaborate with public health activists are unlikely to elevate the (...) longer-term level of trust in this relationship, without significantly fuller or more voluntary compliance by tobacco companies. We conclude that distrust of the industry has served and continues to serve multiple purposes for public health activists. There is little incentive for tobacco control activists to adopt a more trusting stance toward the industry, and significant justification for them to maintain a high level of distrust. (shrink)

The source and inspiration of French “eclecticism” in the first half of last century was historical; its immediate purpose, the reconstitution of philosophical doctrines of the past; its riper though remoter effects, the formation of a tradition which insisted on reinterpretation as an indispensable preliminary to further construction. And it is largely a result of this that we to-day find commonplace the declaration: “A peculiarity of systems that are epoch-making is that their influence should extend beyond their own generation, and (...) that they should prepare, as it were in secret, the thought that is to come.” So far as fuller and comparative scholarship have been applied to the elucidation of Cartesian philosophy and science, the results appear to fall into three groups. First, largely a result of the impetus of Cousin's teaching at the École Normale, there is the ample story of the development and modifications of Cartesianism in Bouillier's Histoire, and the Cartésianisme of Bordas-Demoulin. Later in the century, after the reaction against Cousin, come the invaluable study of Liard, insisting on the greater importance of Descartes' methodology and physics and the priority of the latter over his metaphysics, and the elegant monograph of Fouillee stressing the “voluntarist” tendencies in Descartes. (shrink)

Ellen Fox and collaborators have produced the most detailed description of healthcare ethics practices in the United States available. Some findings are shocking for anyone committed to promoting q...

This book is of fundamental importance in political philosophy as well as in theology, philosophy itself, and history. The fact that it lacks an Index is unconscionable. The book consists of some one hundred six pages of precious correspondence between Strauss and Voegelin, plus a reprinting of Strauss's famous essays "Jerusalem and Athens" and "The Mutual Influence of Theology and Philosophy," with Voegelin's "The Gospel and Culture" and "Immortality: Experience and Symbol." To complete these essays and letters are perceptive, often (...) brilliant, essays by James Wiser, Hans-Georg Gadamer, Stanley Rosen, Timothy Fuller, Ellis Sandoz, Thomas Pangle, and David Walsh. It would be difficult to find a more profound and stimulating book covering the whole history and understanding of faith and reason in Western intellectual history. (shrink)

I propose this: Ellen [a graduate student] laughs because she is re-creating her identity. This theory differs from the others because "identity" is not simply a category that is filled or not, like "incongruity" or "superiority" which become variables in an "if this, then that" explanation. "If there is a sudden incongruity, people will laugh." Rather, identity is a further question, a way of asking, Can I understand Ellen's actions as a theme and variations? Moreover, any such interpretation (...) is itself a part of the interpreter's actions, hence a function of his - in this case, my - identity. The principle is general, but putting it into practice in each instance is unique. Unlike an "if this, then that" which leads to closure, an explanation through identity leads to a continuing dialogue. One asks questions of an individual situation, like Ellen's laughing at [B.] Kliban's cartoons. One gets answers that lead to a fuller understanding of that situation. The answers can be generalized into questions, leading to more and closer questioning and more answers that lead to more questions, all within the general principle of identity re-creation as embodied in the unique situation.Norman N. Holland is the James H. McNulty Professor of English at the State University of New York at Buffalo. He has written a book on the theory of laughter presented in the present essay. His previous contributions to Critical Inquiry are "Literary Interpretation and Three Phases of Psychoanalysis" and "Human Identity". (shrink)

In his new book, Knowledge: The Philosophical Quest in History, Steve Fuller returns to core themes of his program of social epistemology that he first outlined in his 1988 book, Social Epistemology. He develops a new, unorthodox theology and philosophy building upon his testimony in Kitzmiller v. Dover Area School District in defense of intelligent design, leading to a call for maximal human experimentation. Beginning from the theological premise rooted in the Abrahamic religious tradition that we are created in (...) the image of God, Fuller argues that the spark of the divine within us distinguishes us from animals. I argue that Fuller’s recent work takes us away from key insights of his original work. In contrast, I advocate for a program of social epistemology rooted in evolutionary science rather than intelligent design, emphasize a precautionary and ecological approach rather than a proactionary approach that favors risky human experimentation, and attend to our material and sociological embeddedness rather than a transhumanist repudiation of the body. (shrink)

In Plato's Laws, the Athenian Stranger claims that the gods will smile only on a city where the law This passage is the origin of the slogan an abbreviation of which forms our phrase From Plato and Aristotle, through John Adams and John Marshall, down to us, no idea has proven more central to Western political and legal culture. Yet the slogan turns on a very dubious metaphor. Laws do not rule, and the is actually a specific form of rule (...) by men (including, nowadays, a few women). These rulers are not slaves to anything. Furthermore, the construction of the sloganhas unfortunate connotations. It suggests that the personal qualities of the human rulers required to secure the rule of law are nothing more than forbearance and disinterestedness—a resolution to stay out of law's way.Footnotes* I have received helpful comments and criticisms from a number of readers, including the other contributors to this volume and participants in the Georgetown University Law Center faculty workshop. In addition, I should like to thank Brian Bix, Ellen Frankel Paul, Fred Schauer, and Wibren van der Burg for extensive written comments on an earlier draft of this essay. (shrink)