It was, until recently, accepted that the two classes of acetylcholine (ACh) receptors are distinct in an important sense: muscarinic ACh receptors signal via heterotrimeric GTP binding proteins (G proteins), whereas nicotinic ACh receptors (nAChRs) open to allow flux of Na+, Ca2+, and K+ ions into the cell after activation. Here we present evidence of direct coupling between G proteins and nAChRs in neurons. Based on proteomic, biophysical, and functional evidence, we hypothesize that binding to G proteins modulates the activity (...) and signaling of nAChRs in cells. It is important to note that while this hypothesis is new for the nAChR, it is consistent with known interactions between G proteins and structurally related ligand‐gated ion channels. Therefore, it underscores an evolutionarily conserved metabotropic mechanism of G protein signaling via nAChR channels.Also watch the Video Abstract. (shrink)

The development of modern programmable pacemaker-systems has led to a series of questions which until now have apparently not existed in the treatment of cardiac rhythm disturbances. These questions touch especially on the problem of whether the relation which usually exists between a diagnostic step and its therapeutic consequence, namely its therapeutic relevance, is abolished or at least changed.

This book is a collection of secondary essays on America's most important philosophic thinkers—statesmen, judges, writers, educators, and activists—from the colonial period to the present. Each essay is a comprehensive introduction to the thought of a noted American on the fundamental meaning of the American regime.

The contributors to The Moral of the Story, all preeminent political theorists, are unified by their concern with the instructive power of great literature. This thought-provoking combination of essays explores the polyvalent moral and political impact of classic world literatures on public ethics through the study of some of its major figures-including Shakespeare, Dante, Cervantes, Jane Austen, Henry James, Joseph Conrad, Robert Penn Warren, and Dostoevsky. Positing the uniqueness of literature's ability to promote dialogue on salient moral and intellectual virtues, (...) editor Henry T. Edmonson III has culled together a wide-ranging exploration of such fundamental concerns as the abuse of authority, the nature of good leadership, the significance of "middle class virtues" and the needs of adolescents. This collection reinvigorates the study of classic literature as an endeavor that is not only personally intellectually satisfying, but also an inimitable and unique way to enrich public discourse. (shrink)

In highly structured organisational fields individual efforts to deal rationally with uncertainty and constraints tend to lead, in the aggregate, to greater homogeneity in structure, culture and output. Drawing on institutional theory, this paper develops research propositions regarding the nature and scope of corporate social responsibility (CSR) engagement at trade/industry association level. The cases of the water and sewerage and film industries are used in order to test these propositions. The findings suggest that (a) trade associations in more homogeneous industries (...) are more likely to engage with CSR‐related issues; (b) trade associations in industries that face greater external scrutiny and threats to legitimacy are more likely to engage with CSR‐related issues; and (c) trade associations are more likely to engage with those substantive CSR issues that are of greater concern to the industry's most salient stakeholders. The findings also suggest that trade associations may have a greater tendency to engage in symbolic legitimation efforts through CSR if faced with the task of repairing industry legitimacy. (shrink)

In highly structured organisational fields individual efforts to deal rationally with uncertainty and constraints tend to lead, in the aggregate, to greater homogeneity in structure, culture and output. Drawing on institutional theory, this paper develops research propositions regarding the nature and scope of corporate social responsibility (CSR) engagement at trade/industry association level. The cases of the water and sewerage and film industries are used in order to test these propositions. The findings suggest that (a) trade associations in more homogeneous industries (...) are more likely to engage with CSR‐related issues; (b) trade associations in industries that face greater external scrutiny and threats to legitimacy are more likely to engage with CSR‐related issues; and (c) trade associations are more likely to engage with those substantive CSR issues that are of greater concern to the industry's most salient stakeholders. The findings also suggest that trade associations may have a greater tendency to engage in symbolic legitimation efforts through CSR if faced with the task of repairing industry legitimacy. (shrink)

The neural correlates of two hypothesized emotional processing modes, i.e., schematic and propositional modes, were investigated with positron emission tomography. Nineteen subjects performed an emotional mental imagery task while mentally repeating sentences linked to the meaning of the imagery script. In the schematic conditions, participants repeated metaphoric sentences, whereas in the propositional conditions, the sentences were explicit questions about specific emotional appraisals of the imagery scenario. Five types of emotional scripts were proposed to the subjects (happiness, anger, affection, sadness, and (...) a neutral scenario). The results supported the hypothesized distinction between schematic and propositional emotional processing modes. Specifically, schematic mode was associated with increased activity in the ventromedial prefrontal cortex whereas propositional mode was associated with activation of the anterolateral prefrontal cortex. In addition, interaction analyses showed that schematic versus propositional processing of happiness (compared with the neutral scenario) was associated with increased activity in the ventral striatum whereas “schematic anger” was tentatively associated with activation of the ventral pallidum. © 2003 Elsevier Science (USA). All rights reserved. (shrink)

This article addresses the problematic relation between Michel Henry’s phenomenology of life and ethics. More specifically, it asks whether Henry’s account of the self’s transcendental birth in the immanent self-generation of life allows for a sense of individual responsibility. I begin by discussing Henry’s generation of the self and show how the historical essence of the self is structured according to the antinomy of affectivity. I then show how, for Henry, this history of life is full and yet incomplete. Accordingly, (...) life is attracted to growth and this growth happens insofar as living beings proceed through a series of stages of despair. I develop these stages by looking at Henry’s analyses of anxiety, desire, and humility in relation to Kierkegaard. I argue that even though there is already an initial sense of responsibility at work in the earliest stirrings of anxiety, it is only in humility that the self comes to know who it truly is and how it ought to relate to others. Cet article se penche sur la relation problématique entre la phéno-ménologie de la vie et l’éthique de Michel Henry. Plus spécifiquement, nous nous demandons si l’explication de la naissance trans-cendantale du soi dans l’auto-génération immanente de la vie que propose Henry permet de rendre compte d’un sens de la responsabilité personnelle. Nous débutons avec une analyse de la génération du soi chez Henry et montrons comment l’essence historique du soi est structurée selon l’antinomie de l’affectivité. Nous montrons en-suite comment, pour Henry, cette histoire du soi est pleine bien qu’incomplète. En conséquence, la vie est attirée par la croissance, et cette croissance se produit dans la mesure où les êtres vivants passent à travers une série de stades du désespoir. Nous dévelop-pons ces divers stades en nous tournant vers les analyses que fait Henry de l’angoisse, du désir, et de l’humilité en relation avec Kierkegaard. Nous soutenons que même s’il y a déjà un sens initial de la responsabilité à l’oeuvre dans le premier éveil de l’angoisse, c’est seulement en atteignant le stade de l’humilité que le soi en vient à savoir qui il est vraiment et comment il doit se rapporter aux autres. (shrink)

This paper explores the ways that Daniel C. Dennett’s bestselling 2006 book Breaking the Spell traffics in a set of distinctly American presumptions about the relationship between religion and science. In this Americanized atheism, religion is presumed to be a set of logically organized propositional beliefs–a misbegotten science in need of correction or elimination. I show that a convergent critique, drawing on both evolutionary theory and deconstruction, highlights the limitations of this approach. This convergence highlights the theme of accident in (...) both pluralist evolutionary biology and continental philosophy of religion. Thematizing accident opens up a new conversational space between a deconstructive approach to religion and postadaptationist evolutionary theory, with implications not only for a philosophical understanding of religion, but for new, postsecular atheisms. (shrink)

This introduction a) presents organized religion as a source of "spiritual goods" and briefly summarizes each of the seventeen tradition-centeredarticles; b) explains why organized religion merits the attention of business ethics; c) categorizes the articles according to rubrics useful for teaching and research; d) further explains the value of these essays to academic researchers, business practitioners, and spiritual seekers.

This introduction a) presents organized religion as a source of "spiritual goods" and briefly summarizes each of the seventeen tradition-centeredarticles; b) explains why organized religion merits the attention of business ethics; c) categorizes the articles according to rubrics useful for teaching and research; d) further explains the value of these essays to academic researchers, business practitioners, and spiritual seekers.

Coronary by-pass surgery has been performed in hundreds of thousands of patients in the last 15 years with a high standard of technical and surgical perfection. The indications for this kind of surgery, however, are still controversial because in spite of many retrospective and several prospective studies it cannot be proven convincingly that in a given patient this surgical procedure will prolong life or prevent myocardial infarction. The present attempt to analyze the causes for this controversy shows that the main (...) reasons for this uncertainty lie: (a) in the enigma of the underlying (ischemic heart) disease itself, which is supposed to lend itself to surgical therapy; (b) in the inadequate methods available up until now for characterizing the state of the disease, its probable course, and its pathogenesis; and (c) in the professional group interests which have a momentum of their own. (shrink)

Coronary by-pass surgery has been performed in hundreds of thousands of patients in the last 15 years with a high standard of technical and surgical perfection. The indications for this kind of surgery, however, are still controversial because in spite of many retrospective and several prospective studies it cannot be proven convincingly that in a given patient this surgical procedure will prolong life or prevent myocardial infarction. The present attempt to analyze the causes for this controversy shows that the main (...) reasons for this uncertainty lie: (a) in the enigma of the underlying (ischemic heart) disease itself, which is supposed to lend itself to surgical therapy; (b) in the inadequate methods available up until now for characterizing the state of the disease, its probable course, and its pathogenesis; and (c) in the professional group interests which have a momentum of their own. (shrink)

The prospect of consumable meat produced in a laboratory setting without the need to raise and slaughter animals is both realistic and exciting. Not only could such in vitro meat become popular due to potential cost savings, but it also avoids many of the ethical and environmental problems with traditional meat productions. However, as with any new technology, in vitro meat is likely to face some detractors. We examine in detail three potential objections: 1) in vitro meat is disrespectful, either (...) to nature or to animals; 2) it will reduce the number of happy animals in the world; and 3) it will open the door to cannibalism. While each objection has some attraction, we ultimately find that all can be overcome. The upshot is that in vitro meat production is generally permissible and, especially for ethical vegetarians, worth promoting. (shrink)

This article explores Franz Brentano's opposition to papal infallibility, and sets this in the context of his development as a Catholic scholar. An active participant in the Catholic revival of the nineteenth century, Brentano contributed to the emergence of neoscholasticism through his philosophical rehabilitation of Aristotle. Brentano ultimately left the Church however as the result of intensive scrutiny of his faith occasioned by his analysis of infallibility. This article explores this crisis of faith by analyzing, for the first time, Brentano's (...) position on papal infallibility, and suggesting ways that it informed his philosophical development. (shrink)

Ethical decision-making frameworks assist in identifying the issues at stake in a particular setting and thinking through, in a methodical manner, the ethical issues that require consideration as well as the values that need to be considered and promoted. Decisions made about the use, sharing, and re-use of big data are complex and laden with values. This paper sets out an Ethics Framework for Big Data in Health and Research developed by a working group convened by the Science, Health and (...) Policy-relevant Ethics in Singapore Initiative. It presents the aim and rationale for this framework supported by the underlying ethical concerns that relate to all health and research contexts. It also describes a set of substantive and procedural values that can be weighed up in addressing these concerns, and a step-by-step process for identifying, considering, and resolving the ethical issues arising from big data uses in health and research. This Framework is subsequently applied in the papers published in this Special Issue. These papers each address one of six domains where big data is currently employed: openness in big data and data repositories, precision medicine and big data, real-world data to generate evidence about healthcare interventions, AI-assisted decision-making in healthcare, public-private partnerships in healthcare and research, and cross-sectoral big data. (shrink)

For people to contribute to discourse, they must do more than utter the right sentence at the right time. The basic requirement is that they add to their common ground in an orderly way. To do this, we argue, they try to establish for each utterance the mutual belief that the addressees have understood what the speaker meant well enough for current purposes. This is accomplished by the collective actions of the current contributor and his or her partners, and these (...) result in units of conversation called contributions. We present a model of contributions and show how it accounts for a variety of features of everyday conversations. (shrink)

The COVID-19 pandemic has both exposed and created deep rifts in society. It has thrust us into deep ethical thinking to help justify the difficult decisions many will be called upon to make and to protect from decisions that lack ethical underpinnings. This paper aims to highlight ethical issues in six different areas of life highlighting the enormity of the task we are faced with globally. In the context of COVID-19, we consider health inequity, dilemmas in triage and allocation of (...) scarce resources, ethical issues associated with research, ethical considerations relating to tracing apps, and exit strategies such as immunity passports and COVID-19 vaccines. Finally, we consider environmental issues in light of COVID-19. The paper also offers some ethical reflection on these areas as many parts of the world contemplate the recovery phase. (shrink)

The predominant view is that a study using health data is observational research and should require individual consent unless it can be shown that gaining consent is impractical. But recent arguments have been made that citizens have an ethical obligation to share their health information for research purposes. In our view, this obligation is sufficient ground to expand the circumstances where secondary use research with identifiable health information is permitted without explicit subject consent. As such, for some studies the Institutional (...) Review Board/Research Ethics Committee review process should not assess the practicality of gaining consent for data use. Instead the review process should focus on assessing the public good of the research, public engagement and transparency. (shrink)

High degrees of uncertainty and a lack of effective therapeutic treatments have characterized the COVID-19 pandemic and the provision of drug products outside research settings has been controversial. International guidelines for providing patients with experimental interventions to treat infectious diseases outside of clinical trials exist but it is unclear if or how they should apply in settings where clinical trials and research are strongly regulated. We propose the Professional Oversight of Emergency-Use Interventions and Monitoring System as an alternative pathway based (...) on guidance developed for the ethical provision of experimental interventions to treat COVID-19 in Singapore. We support our proposal with justifications that establish moral duties for physicians to record outcomes data and for institutions to establish monitoring systems for reporting information on safety and effectiveness to the relevant authorities. Institutions also have a duty to support generation of evidence for what constitutes good clinical practice and so should ensure the unproven intervention is made the subject of research studies that can contribute to generalizable knowledge as soon as practical and that physicians remain committed to supporting learning health systems. We outline key differences between POEIMS and other pathways for the provision of experimental interventions in public health emergencies. (shrink)

The future of health research will be characterised by three continuing trends: rising demand for health data; increasing impracticability of obtaining specific consent for secondary research; and decreasing capacity to effectively anonymise data. In this context, governments, clinicians and the research community must demonstrate that they can be responsible stewards of health data. IRBs and RECs sit at heart of this process because in many jurisdictions they have the capacity to grant consent waivers when research is judged to be of (...) particular value. However, several different terms are used to refer to this value, indicating a lack of conceptual clarity regarding the appropriate test for access to health data for research without consent. In this paper we do three things. First we describe the current confusion and instability in terminology relating to public interest in the context of consent waivers. Second we argue for harmonisation of terminology on the grounds of clarity, transparency and consistency. Third we argue that the term ‘public interest’ best reflects the normative work required to justify consent waivers because it is the broadest of the competing terms. ‘Public interest’ contains within its scope positive and negative implications of a study, as well as welfare, justice and rights considerations. In making this argument, we explain the normative basis for consent waivers, and provide a starting place for further discussion about the precise conditions in which a given study can be said to advance the public interest. Ipsos MORI study found that: … the public would be broadly happy with administrative data linking for research projects provided Those projects have social value, broadly defined. Data are de-identified. Data are kept secure. Businesses are not able to access the data for profit. (shrink)

We study the values on which managers of small and medium-sized enterprises (SMEs) draw when constructing their personal and organizational-level engagement with environmental issues, particularly climate change. Values play an important mediating role in business environmental engagement, but relatively little research has been conducted on individual values in smaller organizations. Using the Schwartz Value System (SVS) as a framework for a qualitative analysis, we identify four “ideal-types” of SME managers and provide rich descriptions of the ways in which values shape (...) their constructions of environmental engagement. In contrast to previous research, which is framed around a binary divide between self-enhancing and self-transcending values, our typology distinguishes between individuals drawing primarily on Power or on Achievement values and indicates how a combination of Achievement and Benevolence values is particularly significant in shaping environmental engagement. This demonstrates the theoretical usefulness of focusing on a complete range of values. Implications for policy and practice are discussed. (shrink)

We define and study a new notion called k-immunity that lies between immunity and hyperimmunity in strength. Our interest in k-immunity is justified by the result that θ does not k-tt reduce to a k-immune set, which improves a previous result by Kobzev [7]. We apply the result to show that Φ′ does not btt-reduce to MIN, the set of minimal programs. Other applications include the set of Kolmogorov random strings, and retraceable and regressive sets. We also give a new (...) characterization of effectively simple sets and show that simple sets are not btt-cuppable. (shrink)

The development of some COVID-19 vaccines by private companies like Moderna and Sanofi-GSK has been substantially funded by various governments. While the Sanofi CEO has previously suggested that countries that fund this development ought to be given some priority, this suggestion has not been taken seriously in the literature. Considerations of nationalism, sustainability, need, and equitability have been more extensively discussed with respect to whether and how much a country is entitled to advance purchase orders of the vaccine under conditions (...) of absolute scarcity. Yet, little attention has been paid to whether prior investment into developing a vaccine entitles a country to some priority with respect to these orders. Moreover, while not a majority view, some survey results show that a significant minority of the populace does endorse some view like this. This article argues that the minority have a point: recognizing funder countries some priority is justified by the weak Lockean claim (WLC). According to the WLC, the fact that someone has contributed to the development of something gives them some entitlement to the resultant product. This article will defend the WLC, and address objections to the argument, including those pertaining to questions of historical injustice and medical need. This argument does not imply an unconstrained entitlement. Rather, contribution to development is one morally relevant factor that must be tempered by and weighed against potentially more substantial claims to priority based on need, equity, and other considerations. (shrink)

This paper argues that one problem that besets black-box AI is that it lacks algorithmic justifiability. We argue that the norm of shared decision making in medical care presupposes that treatment decisions ought to be justifiable to the patient. Medical decisions are justifiable to the patient only if they are compatible with the patient’s values and preferences and the patient is able to see that this is so. Patient-directed justifiability is threatened by black-box AIs because the lack of rationale provided (...) for the decision makes it difficult for patients to ascertain whether there is adequate fit between the decision and the patient’s values. This paper argues that achieving algorithmic transparency does not help patients bridge the gap between their medical decisions and values. We introduce a hypothetical model we call Justifiable AI to illustrate this argument. Justifiable AI aims at modelling normative and evaluative considerations in an explicit way so as to provide a stepping stone for patient and physician to jointly decide on a course of treatment. If our argument succeeds, we should prefer these justifiable models over alternatives if the former are available and aim to develop said models if not. (shrink)

The development of some COVID-19 vaccines by private companies like Moderna and Sanofi-GSK has been substantially funded by various governments. While the Sanofi CEO has previously suggested that countries that fund this development ought to be given some priority, this suggestion has not been taken seriously in the literature. Considerations of nationalism, sustainability, need, and equitability have been more extensively discussed with respect to whether and how much a country is entitled to advance purchase orders of the vaccine under conditions (...) of absolute scarcity. Yet, little attention has been paid to whether prior investment into developing a vaccine entitles a country to some priority with respect to these orders. Moreover, while not a majority view, some survey results show that a significant minority of the populace does endorse some view like this. This article argues that the minority have a point: recognizing funder countries some priority is justified by the weak Lockean claim (WLC). According to the WLC, the fact that someone has contributed to the development of something gives them some entitlement to the resultant product. This article will defend the WLC, and address objections to the argument, including those pertaining to questions of historical injustice and medical need. This argument does not imply an unconstrained entitlement. Rather, contribution to development is one morally relevant factor that must be tempered by and weighed against potentially more substantial claims to priority based on need, equity, and other considerations. (shrink)

An adequate theory of rights ought to forbid the harming of animals to promote trivial interests of humans, as is often done in the animal-user industries. But what should the rights view say about situations in which harming some animals is necessary to prevent intolerable injustices to other animals? I develop an account of respectful treatment on which, under certain conditions, it’s justified to intentionally harm some individuals to prevent serious harm to others. This can be compatible with recognizing the (...) inherent value of the ones who are harmed. My theory has important implications for contemporary moral issues in nonhuman animal ethics, such as the development of cultured meat and animal research. (shrink)

In their response to ‘Public interest in health data research: laying out the conceptual groundwork’, Grewal and Newson critique us for inattention to the law and putting forward an impracticably broad conceptual understanding of public interest. While we agree more work is needed to generate a workable framework for Institutional Review Boards/Research Ethics Committees, we would contend that this should be grounded on a broad conception of public interest. This broadness facilitates regulatory agility, and is already reflected by some current (...) frameworks such as that found in the guidelines approved under Australia’s Privacy Act. It remains unclear which elements of our broad account Grewal and Newson would reject, or indeed where the substantive disagreement with our position lies. (shrink)

Regrettably, in the original version of this article the name of one of the authors was spelt incorrectly. "Li Yan Hsu" should be "Li Yang Hsu".