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)

Pendant l’été 2012, les artistes Ellen Rothenberg et Délia Popa participèrent à un projet d’échange culturel avec une famille rom vivant dans une petite communauté agraire du comté de Sibiu, vieille région de Transylvanie. Le deuxième volet de ce projet comprenait une exposition des œuvres inspirées par cette expérience, dans les Galeries d’Art Contemporain du Musée National de Brukenthal, à l’automne 2013. Intitulée « Chelen Amenca (Danse avec nous) », cette exposition fut organisée par la c...

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)

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 ...

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)

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)

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)

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)

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)

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...

Although high-performance human resource practices do not directly affect corporate social performance strengths, they do positively affect CSP strengths in companies that are highly innovative or have high levels of slack. High-performance human resource management practices also directly and negatively affect CSP concerns. Drawing on the resource-based view and using secondary data from an objective, third-party database, the authors develop and test hypotheses about how high-performance HRM affects a company’s CSP strengths and concerns. Findings suggest that HRM and innovation are (...) important capabilities because they create and enhance other capabilities. (shrink)

By Jerome Rothenberg. Contributions by Steven Clay, Rodney Phillips.

Ellen Meiksins Wood is a leading contemporary political theorist who has elaborated an innovative approach to the history of political thought, the social history of political theory .

Although affective facial pictures are widely used in emotion research, standardised affective stimuli sets are rather scarce, and the existing sets have several limitations. We therefore conducted a validation study of 490 pictures of human facial expressions from the Karolinska Directed Emotional Faces database (KDEF). Pictures were evaluated on emotional content and were rated on an intensity and arousal scale. Results indicate that the database contains a valid set of affective facial pictures. Hit rates, intensity, and arousal of the 20 (...) best KDEF pictures for each basic emotion are provided in an appendix. (shrink)

This document presents the Bonn PRINTEGER Consensus Statement: Working with Research Integrity—Guidance for research performing organisations. The aim of the statement is to complement existing instruments by focusing specifically on institutional responsibilities for strengthening integrity. It takes into account the daily challenges and organisational contexts of most researchers. The statement intends to make research integrity challenges recognisable from the work-floor perspective, providing concrete advice on organisational measures to strengthen integrity. The statement, which was concluded February 7th 2018, provides guidance on (...) the following key issues: § 1.Providing information about research integrity § 2.Providing education, training and mentoring § 3.Strengthening a research integrity culture § 4.Facilitating open dialogue § 5.Wise incentive management § 6.Implementing quality assurance procedures § 7.Improving the work environment and work satisfaction § 8.Increasing transparency of misconduct cases § 9.Opening up research § 10.Implementing safe and effective whistle-blowing channels § 11.Protecting the alleged perpetrators § 12.Establishing a research integrity committee and appointing an ombudsperson § 13.Making explicit the applicable standards for research integrity. (shrink)

Putting the ethical tools of philosophy to work, Ellen K. Feder seeks to clarify how we should understand "the problem" of intersex. Adults often report that medical interventions they underwent as children to "correct" atypical sex anatomies caused them physical and psychological harm. Proposing a philosophical framework for the treatment of children with intersex conditions—one that acknowledges the intertwined identities of parents, children, and their doctors—Feder presents a persuasive moral argument for collective responsibility to these children and their families.

Offers information on "Philosophy Now" magazine, published quarterly in London, England. Includes subscription details, an events calendar, and online discussion forums. Highlights features and news from the current issue.

Some health care organizations allow physicians to withhold cardiopulmonary resuscitation from a patient, despite patient or surrogate requests that it be provided, when they believe it will be more harmful than beneficial. Such cases usually involve patients with terminal diagnoses whose medical teams argue that aggressive treatments are medically inappropriate or likely to be harmful. Although there is state-to-state variability and a considerable judicial gray area about the conditions and mechanisms for refusals to perform CPR, medical teams typically follow a (...) set of clearly defined procedures for these decisions. The procedures are based on the principle of nonmaleficence and typically include consultation with hospital ethics committees, reflecting the guidelines of relevant professional associations. Ethical debates about when CPR can and should be limited tend to rely more on discussions of theory, principles, and case studies than systematic empirical study of the situations in which such limitations are applied. Sociologists of bioethics call for empirical study, arguing that what ethicists and health professionals believe they are doing when they draft policies or invoke principles does not always mirror what is happening on the ground. In this article, we begin the task of modeling the empirical analyses sociologists call for, focusing on a cohort at Massachusetts General Hospital. We inductively analyzed ethics committee notes and medical records of nineteen patients whose surrogates did not accept the decision to withhold CPR. (shrink)

Philosophical questions surrounding skill and expertise can be traced back as far as Ancient Greece, China, and India. In the twentieth century skilled action was an important factor in the work of phenomenologists such as Heidegger and Merleau-Ponty and analytic philosophers including Gilbert Ryle. However, as a subject in its own right it has, until now, remained largely in the background. The Routledge Handbook of Philosophy of Skill and Expertise is an outstanding reference source and the first major collection of (...) its kind, reflecting the explosion of interest in the topic recent years. Comprising thirty-nine chapters written by leading international contributors, the Handbook is organised into six clear parts: Skill in the History of Philosophy Skill in Epistemology Skill, intelligence, and agency Skill in Perception, Imagination, and Emotion Skill, Language, and, Social Cognition Skill and Expertise in Normative Philosophy. Essential reading for students and researchers in philosophy of mind and psychology, epistemology and ethics, The Routledge Handbook of Philosophy of Skill and Expertise is also suitable for those in related disciplines such as social psychology and cognitive science. It is also relevant to those who are interested in conceptual issues underlying skill and expertise in fields such as sport, the performing arts, and medicine. (shrink)

One antidote to moral distress is stronger moral agency—that is, an enhanced ability to act to bring about change. The Clinical Ethics Residency for Nurses, an educational program developed and run in two large northeastern academic medical centers with funding from the Health Resources and Services Administration, intended to strengthen nurses’ moral agency. Drawing on Improving Competencies in Clinical Ethics Consultation: An Education Guide, by the American Society for Bioethics and Humanities, and on the goals of the nursing profession, CERN (...) sought to change attitudes, increase knowledge, and develop skills to act on one's knowledge. One of the key insights the faculty members brought to the design of this program is that knowledge of clinical ethics is not enough to develop moral agency. In addition to lecture‐style classes, CERN employed a variety of methods based in adult learning theory, such as active application of ethics knowledge to patient scenarios in classroom discussion, simulation, and the clinical practicum. Overwhelmingly, the feedback from the participants (sixty‐seven over three years of the program) indicated that CERN achieved transformative learning. (shrink)

This study examines the extent to which scientific and biomedical journals have adopted conflict of interest (COI) policies for authors, and whether the adoption and content of such policies leads to the publishing of authors’ financial interest disclosure statements by such journals. In particular, it reports the results of a survey of journal editors about their practices regarding COI disclosures. About 16 percent of 1396 highly ranked scientific and biomedical journals had COI policies in effect during 1997. Less than 1 (...) percent of the articles published during that year in the journals with COI policies contained any disclosures of author personal financial interests while nearly 66 percent of the journals had zero disclosures of author personal financial interests. Nearly three fourths of journal editors surveyed usually publish author disclosure statements suggesting that low rates of personal financial disclosures are either a result of low rates of author financial interest in the subject matter of their publications or poor compliance by authors to the journals’ COI policies. (shrink)

There is strong theoretical support for a relationship between various characteristics of religiousness and attitudes towards business ethics. This paper examines three frequently- studied dimensions of religiousness (fundamentalism, conservatism, and intrinsic religiousness) and their ability to predict students' willingness to behave unethically. Because prior research indicated a possible relationship between the religious affiliation of an institution and its members' ethical orientation, we studied students at universities with three different types of religious affiliation: evangelical, Catholic, and none.Results of the study lend (...) support to a negative relationship between the above-mentioned dimensions of religiousness and willingness to behave unethically. In addition, students at the Evangelical university were far less willing to engage in unethical behavior than were students at either the Catholic or the unaffiliated institutions. (shrink)