Epistasis plays an important role in the genetic architecture of common human diseases and can be viewed from two perspectives, biological and statistical, each derived from and leading to different assumptions and research strategies. Biological epistasis is the result of physical interactions among biomolecules within gene regulatory networks and biochemical pathways in an individual such that the effect of a gene on a phenotype is dependent on one or more other genes. In contrast, statistical epistasis is defined as deviation from (...) additivity in a mathematical model summarizing the relationship between multilocus genotypes and phenotypic variation in a population. The goal of this essay is to review definitions and examples of biological and statistical epistasis and to explore the relationship between the two. Specifically, we present and discuss the following two questions in the context of human health and disease. First, when does statistical evidence of epistasis in human populations imply underlying biomolecular interactions in the etiology of disease? Second, when do biomolecular interactions produce patterns of statistical epistasis in human populations?Answers to these two reciprocal questions will provide an important framework for using genetic information to improve our ability to diagnose, prevent and treat common human diseases. We propose that systems biology will provide the necessary information for addressing these questions and that model systems such as bacteria, yeast and digital organisms will be a useful place to start. BioEssays 27:637–646, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Pleiotropy, in which one mutation causes multiple phenotypes, has traditionally been seen as a deviation from the conventional observation in which one gene affects one phenotype. Epistasis, or gene–gene interaction, has also been treated as an exception to the Mendelian one gene–one phenotype paradigm. This simplified perspective belies the pervasive complexity of biology and hinders progress toward a deeper understanding of biological systems. We assert that epistasis and pleiotropy are not isolated occurrences, but ubiquitous and inherent properties of biomolecular networks. (...) These phenomena should not be treated as exceptions, but rather as fundamental components of genetic analyses. A systems level understanding of epistasis and pleiotropy is, therefore, critical to furthering our understanding of human genetics and its contribution to common human disease. Finally, graph theory offers an intuitive and powerful set of tools with which to study the network bases of these important genetic phenomena. (shrink)

Equipoise is an essential condition to justify a clinical trial. The term, describes a state of uncertainty: the data suggest but do not prove a drug's safety and efficacy The only way to resolve this uncertainty is further study In many cases, a clinical trial seems to be the most efficient way to prove safety and efficacy Equipoise is therefore not an esoteric philosophic construct applied to research ethics. Rather, since it is vital for the justification of clinical trials, it (...) is part of how society regulates medical progress. Where there is equipoise, drug design and development proceeds according to Food and Drug Administration and Health and Human Services regulations. When that equipoise ends, a drug is either not approved or becomes standard care. (shrink)

Equipoise is an essential condition to justify a clinical trial. The term, describes a state of uncertainty: the data suggest but do not prove a drug's safety and efficacy The only way to resolve this uncertainty is further study In many cases, a clinical trial seems to be the most efficient way to prove safety and efficacy Equipoise is therefore not an esoteric philosophic construct applied to research ethics. Rather, since it is vital for the justification of clinical trials, it (...) is part of how society regulates medical progress. Where there is equipoise, drug design and development proceeds according to Food and Drug Administration and Health and Human Services regulations. When that equipoise ends, a drug is either not approved or becomes standard care. (shrink)

While experience often affords important knowledge and insight that is difficult to garner through observation or testimony alone, it also has the potential to generate conflicts of interest and unrepresentative perspectives. We call this tension the paradox of experience. In this paper, we first outline appeals to experience made in debates about access to unproven medical products and disability bioethics, as examples of how experience claims arise in bioethics and some of the challenges raised by these claims. We then motivate (...) the idea that experience can be an asset by appealing to themes in feminist and moral epistemology, distinguishing between epistemic and justice-based appeals. Next, we explain the concern that experience may be a liability by appealing to empirical work on cognitive biases and theoretical work about the problem of partial representation. We conclude with preliminary recommendations for addressing the paradox and offer several questions for future discussion. (shrink)

Individualism is one of most criticized and least understood ideas in social and political thought. Is individualism the ability to act independently amidst a web of social forces? A vital element of personal liberty and a shield against conformity? Does it lead to or away from unifying individuals with communities? Individualism: A Reader provides a wealth of illuminating essays from the 17th to the early 20th centuries. In 26 selections from 25 writers individualism is explained and defended, often from unusual (...) perspectives. This anthology includes not only selections from well-known writers, but also many lesser-known pieces--reprinted here for the first time--by philosophers, social theorists, and economists who have been overlooked in standard accounts of individualism. The depth and complexity of ideas about individualism are reflected in the six sections in this collection. The first examines individuality generally, with the following five detailing social, moral, political, religious, and economic individualism. Throughout, individualism is analyzed and defended through the lenses of classical liberalism, free-market libertarianism, individual anarchism, voluntary socialism, religious individualism, abolitionism, free thought, and radical feminism. Both richly historical and sharply contemporary, Individualism: A Reader provides a multitude of perspectives and insights on personal liberty and the history of freedom. (shrink)

Singularity Hypotheses: A Scientific and Philosophical Assessment offers authoritative, jargon-free essays and critical commentaries on accelerating technological progress and the notion of technological singularity. It focuses on conjectures about the intelligence explosion, transhumanism, and whole brain emulation. Recent years have seen a plethora of forecasts about the profound, disruptive impact that is likely to result from further progress in these areas. Many commentators however doubt the scientific rigor of these forecasts, rejecting them as speculative and unfounded. We therefore invited prominent (...) computer scientists, physicists, philosophers, biologists, economists and other thinkers to assess the singularity hypotheses. Their contributions go beyond speculation, providing deep insights into the main issues and a balanced picture of the debate. (shrink)

Differences across fields and experience levels are frequently considered in discussions of ethical decision making and ethical behavior. In the present study, doctoral students in the health, biological, and social sciences completed measures of ethical decision making. The effects of field and level of experience with respect to ethical decision making, metacognitive reasoning strategies, social-behavioral responses, and exposure to unethical events were examined. Social and biological scientists performed better than health scientists with respect to ethical decision making. Furthermore, the ethical (...) decision making of health science students decreased as experience increased. Moreover, these effects appeared to be linked to the specific strategies underlying participants' ethical decision making. The implications of these findings for ethical decision making are discussed. (shrink)

Volume 20, Issue 2, February 2020, Page 66-68.

Hastings Center Report, Volume 52, Issue 1, Page 42-50, January/February 2022.

Introduction: What is the critical spirit?--Utopianism, ancient and modern, by M.I. Finley.--Primitive society in its many dimensions, by S. Diamond.--Manicheanism in the Enlightenment, by R.H. Popkin.--Schopenhauer today, by M. Horkheimer.--Beginning in Hegel and today, by K.H. Wolff.--The social history of ideas: Ernst Cassirer and after, by P. Gay.--Policies of violence, from Montesquieu to the Terrorist, by E.V. Walter.--Thirty-nine articles: toward a theory of social theory, by J.R. Seeley.--History as private enterprise, by H. Zinn.--From Socrates to Plato, by H. Meyerhoff.--Rational society (...) and irrational art, by H. Read.--The quest for the Grail; Wagner and Morris, by C.E. Schorske.--Valéry; Monsieur Teste, by L. Goldmann.--History and existentialism in Sartre, by L. Krieger.--German popular biographies; culture's bargain counter, by L. Lowenthal.--The Rechtsstaat as magic wall, by O. Kirchheimer. (shrink)

Bibliographical footnotes. Introduction: What is the critical spirit?--Utopianism, ancient and modern, by M.I. Finley.--Primitive society in its many dimensions, by S. Diamond.--Manicheanism in the Enlightenment, by R.H. Popkin.--Schopenhauer today, by M. Horkheimer.--Beginning in Hegel and today, by K.H. Wolff.--The social history of ideas: Ernst Cassirer and after, by P. Gay.--Policies of violence, from Montesquieu to the Terrorist, by E.V. Walter.--Thirty-nine articles: toward a theory of social theory, by J.R. Seeley.--History as private enterprise, by H. Zinn.--From Socrates to Plato, by H. (...) Meyerhoff.--Rational society and irrational art, by H. Read.--The quest for the Grail; Wagner and Morris, by C.E. Schorske.--ValeÌ ry; Monsieur Teste, by L. Goldmann.--History and existentialism in Sartre, by L. Krieger.--German popular biographies; culture's bargain counter, by L. Lowenthal.--The Rechtsstaat as magic wall, by O. Kirchheimer. Revolution from above: some notes on the decision to collectivize Soviet agriculture, by E.H. Carr.--Winston Churchill, power politician and counter revolutionary, by A.J. Mayer.--Brahmins and business, 1870-1914; a hypothesis on the social basis of success in American history, by G. Kolko.--On the limits of professional thought, by M.R. Stein.--The limits of integration, by P. Mattick.--The society nobody wants; a look beyond Marxism and liberalism.--Marcuse as teacher, by W. Leiss, J.D. Ober and E. Sherover.--Marcuse bibliography, by W. Leiss, J.D. Ober and E. Sherover (p. 427-433). (shrink)

In recent years, we have seen a new concern with ethics training for research and development professionals. Although ethics training has become more common, the effectiveness of the training being provided is open to question. In the present effort, a new ethics training course was developed that stresses the importance of the strategies people apply to make sense of ethical problems. The effectiveness of this training was assessed in a sample of 59 doctoral students working in the biological and social (...) sciences using a pre-post design with follow-up and a series of ethical decision-making measures serving as the outcome variable. Results showed not only that this training led to sizable gains in ethical decision making but also that these gains were maintained over time. The implications of these findings for ethics training in the sciences are discussed. (shrink)

Ethical decision making measures are widely applied as the principal dependent variable used in studies of research integrity. However, evidence bearing on the internal and external validity of these measures is not available. In this study, ethical decision making measures were administered to 102 graduate students in the biological, health, and social sciences, along with measures examining exposure to ethical breaches and the severity of punishments recommended. The ethical decision making measure was found to be related to exposure to ethical (...) events and the severity of punishments awarded. The implications of these findings for the application of ethical decision making measures are discussed. (shrink)

It is commonly held that early career experiences influence ethical behavior. One way early career experiences might operate is to influence the decisions people make when presented with problems that raise ethical concerns. To test this proposition, 102 first-year doctoral students were asked to complete a series of measures examining ethical decision making along with a series of measures examining environmental experiences and climate perceptions. Factoring of the environmental measure yielded five dimensions: professional leadership, poor coping, lack of rewards, limited (...) competitive pressure, and poor career direction. Factoring of the climate inventory yielded four dimensions: equity, interpersonal conflict, occupational engagement, and work commitment. When these dimensions were used to predict performance on the ethical decision-making task, it was found that the environmental dimensions were better predictors than the climate dimensions. The implications of these findings for research on ethical conduct are discussed. (shrink)

Mystical Theology and Platonism in the Time of Cusanus engages with the history of mystical theology and Neoplatonic philosophy through the lens of the 15th century philosopher and theologian, Nicholas of Cusa. The volume comprises nineteen essays that break down the barriers between medieval and Renaissance studies, reinterpreting Cusanus’ place in the history of thought by exploring the archive that informed his thinking, while also interrogating his works by exploring them from the standpoint of their later reception by modern philosophers (...) and theologians. The volume also offers tribute to the career of Donald F. Duclow, a leading scholar in the field of Cusanus studies in particular and of the history of mystical theology and Neoplatonic philosophy more generally. (shrink)

Literary and philosophical reflections combine with true-life farm anecdotes to offer commentary on seeking the good life in the modern age.

How should clinical ethicists be trained? Scholars have stated that clinical ethics fellowships create well-trained, competent ethicists. While this appears intuitive, few features of fellowship programs have been publicly discussed, let alone debated. In this paper, we examine how fellowships can foster effective mentoring relationships. These relationships provide the foundation for the fellow’s transition from novice to competent professional. In this essay, we begin by discussing our pedagogical commitments. Next, we describe the structures our program has created to assist our (...) fellows in becoming competent ethicists. We then outline the kinds of knowledge, skills, and professional attributes mentors should possess. Following this, we focus on the knowledge, skills, and professional attributes that fellows develop as they co-create effective mentoring relationships. We will not prescribe a single approach to fellowship training; instead, our perspective will, we hope, become a catalyst for further conversation on training and mentoring clinical ethics fellows. (shrink)

This editorial, introducing the Journal for Theoretical & Marginal Mathematics Education, is historically situated in a moment when the field of mathematics education research is on the precipice of acknowledging that the old world is dying. That is to say, the way research has been done before is no longer adequate for operating within the White, Colonial, cis-hetero Patriarchal, Abled Capitalist dystopia we find ourselves. This inadequacy is, however, not a reason for despair but instead for celebration. Instead of directing (...) our resources towards reifying existing norms and structures, towards adopting exhausted methods and theories—as is the way of the old world—we can instead foster a ‘new aesthetics’ of mathematics education research, wherein we remake the very material that constitutes mathematics education research itself. In doing so, we engage with the politics of the margins of mathematics education research. We discuss the critical, philosophical, and psychoanalytic as three potential, but non-exhaustive, departures from mathematics education research as it has been. Each of these marginal approaches, in their own way, points to the ways that presuming a fixed mathematics education research enacts exclusionary politics and precludes change. Let this be our manifesto, written from the margins, for a more root-grasping, more self-reflective, and freer mathematics education research. (shrink)

Moss (2018) argues that rational agents are best thought of not as having degrees of belief in various propositions but as having beliefs in probabilistic contents, or probabilistic beliefs. Probabilistic contents are sets of probability functions. Probabilistic belief states, in turn, are modeled by sets of probabilistic contents, or sets of sets of probability functions. We argue that this Mossean framework is of considerable interest quite independently of its role in Moss’ account of probabilistic knowledge or her semantics for epistemic (...) modals and probability operators. It is an extremely general model of uncertainty. Indeed, it is at least as general and expressively powerful as every other current imprecise probability framework, including lower probabilities, lower previsions, sets of probabilities, sets of desirable gambles, and choice functions. In addition, we partially answer an important question that Moss leaves open, viz., why should rational agents have consistent probabilistic beliefs? We show that an important subclass of Mossean believers avoid Dutch bookability iff they have consistent probabilistic beliefs. (shrink)

What has been the historical relationship between set theory and logic? On the one hand, Zermelo and other mathematicians developed set theory as a Hilbert-style axiomatic system. On the other hand, set theory influenced logic by suggesting to Schröder, Löwenheim and others the use of infinitely long expressions. The questions of which logic was appropriate for set theory - first-order logic, second-order logic, or an infinitary logic - culminated in a vigorous exchange between Zermelo and Gödel around 1930.

This article considers the emergence of world environmental history as a rapidly growing but undertheorized research field. Taking as its central problematic the gap between the fertile theorizations of environmentally-oriented social scientists and the empirically rich studies of world environmental historians, the article argues for a synthesis of theory and history in the study of longue dureesocio-ecological change. This argument proceeds in three steps. First, I offer an ecological reading of Immanuel Wallerstein's The Modern World-System. Wallerstein's handling of the ecological (...) dimensions of the transition from feudalism to capitalism is suggestive of a new approach to world environmental history. Second, I contend that Wallerstein's theoretical insights may be effectively complemented by drawing on Marxist notions of value and above all the concept of “metabolic rift,” which emphasize the importance of productive processes and regional divisions of labor within the modern world-system. Finally, I develop these theoretical discussions in a short environmental history of the two great “commodity frontiers” of early capitalism – the sugar plantation and the silver mining complex. (shrink)