Randomized controlled trial trial designs exist on an explanatory-pragmatic spectrum, depending on the degree to which a study aims to address a question of efficacy or effectiveness. As conceptualized by Schwartz and Lellouch in 1967, an explanatory approach to trial design emphasizes hypothesis testing about the mechanisms of action of treatments under ideal conditions, whereas a pragmatic approach emphasizes testing effectiveness of two or more available treatments in real-world conditions. Interest in, and the number of, pragmatic trials has grown substantially (...) in recent years, with increased recognition by funders and stakeholders worldwide of the need for credible evidence to inform clinical decision-making. This increase has been accompanied by the onset of learning healthcare systems, as well as an increasing focus on patient-oriented research. However, pragmatic trials have ethical challenges that have not yet been identified or adequately characterized. The present study aims to explore the views of key stakeholders with respect to ethical issues raised by the design and conduct of pragmatic trials. It is embedded within a large, four-year project that seeks to develop guidance for the ethical design and conduct of pragmatic trials. As a first step, this study will address important gaps in the current empirical literature with respect to identifying a comprehensive range of ethical issues arising from the design and conduct of pragmatic trials. By opening up a broad range of topics for consideration within our parallel ethical analysis, we will extend the current debate, which has largely emphasized issues of consent, to the range of ethical considerations that may flow from specific design choices. Semi-structured interviews with key stakeholders, across multiple jurisdictions, identified based on their known experience and/or expertise with pragmatic trials. We expect that the study outputs will be of interest to a wide range of knowledge users including trialists, ethicists, research ethics committees, journal editors, regulators, healthcare policymakers, research funders and patient groups. All publications will adhere to the Tri-Agency Open Access Policy on Publications. (shrink)

Are we paying enough attention? At least since the nineteenth century, critics have alleged a widespread and profound failure of attentiveness—to others, to ourselves, to the world around us, to what is truly worthy of focus. Why is there such great anxiety over attention? What is at stake in understanding attention and the challenges it faces? This book investigates attention from a range of disciplinary perspectives, including philosophy, history, anthropology, art history, and comparative literature. Each chapter begins with a concrete (...) scene whose protagonists are trying—and often failing—to attend. Authors examine key moments in the history of the study of attention; pose attention as a philosophical problem; explore the links between attention, culture, and technology; and consider the significance of attention for conceptualizations of human subjectivity. Readers encounter nineteenth-century experiments in boredom, ornithologists conveying sound through field notations, wearable attention-enhancing prosthetics, students using online learning platforms, and inquiries into attention as a cognitive state and moral virtue. Amid mounting concern about digital mediation of experience, the rise of “surveillance capitalism,” and the commodification of attention, Scenes of Attention deepens the thinking that is needed to protect the freedom of attention and the forms of life that make it possible. (shrink)

A great achievement makes one’s life go better independently of its results, but what makes an achievement great? A simple answer is—its difficulty. I defend this view against recent, pressing objections by interpreting difficulty in terms of competitiveness. Difficulty is determined not by how hard the agent worked for the end but by how hard others would need to do in order to compete. Successfully reaching a goal is a valuable achievement because it is difficult, and it is difficult because (...) it is competitive. Hence, both virtuosic performances and lucky successes can be valuable achievements. (shrink)

A prominent tradition in Nietzsche scholarship reads his views about will to power as a psychological thesis and his claims about the value of power as an attempt to derive normativity from psychological necessity. This article shows that these interpretations have failed to articulate a cogent reading faithful to Nietzsche’s texts, and so casts doubt on such an approach. My argument bears not only on how we read Nietzsche, but also on the viability of one recent constitutivist reading. After presenting (...) these critical arguments, I consider an original interpretation of will to power in terms of the motivation to grow. This revised interpretation, however, still fails to support the tradition’s derivation of normativity. Thus, I conclude we should look elsewhere for Nietzsche’s normative argument. (shrink)

The real history of the covey of attention-artists who call themselves "The Birds." A great deal of uncertainty--and even some genuine confusion--surrounds the origin, evolution, and activities of the so-called Avis Tertia or "Order of the Third Bird." Sensational accounts of this "attentional cult" emphasize histrionic rituals, tragic trance-addictions, and the covert dissemination of obscurantist ontologies of the art object. Hieratic, ecstatic, and endlessly evasive, the Order attracts sensual misfits and cabalistic aesthetes--both to its ranks, and to its scholarship. In (...) recent years, however, the revisionist work of the research collective ESTAR(SER) has done much to clear the air, bringing archival precision to the history of this covey of attention-artists who call themselves "The Birds." Gathering the best articles of the last twenty years of The Proceedings of ESTAR(SER), this volume represents a landmark in the history of aesthetic practices, and will be a point of departure for future work wading the muddy marshes at the limits of historicism."--Publisher description. (shrink)

From Galileo to the Bhopal tort litigation, Scopes to OncoMouse®, Lysenko to the lie detector, the agonistic and alethic forum of the courtroom has offered unique opportunities to witness science and scientists being made and unmade. Evolving legal systems have consistently been forced to draw on (or defensibly away from) scientific knowledge, scientific methods, and scientific experts in the pursuit of truth and justice. At the same time, courts—in many ways the original site for the production of social facts—have to (...) a significant extent shaped both the theories and the practices of knowledge production central to the emergence of modern science. This Focus section draws together a set of scholars at work on these borrowings and aims to stimulate more research in an important and fast‐expanding area of scholarship. (shrink)

An introductory text on the philosophy of chiropractic, for both chiropractic students and practitioners and those interested in the practice and philosophy of ...

Why does it seem better to be a pauper who becomes a king rather than a king who becomes a pauper even when each life contains an equivalent sum of goods to the other? Many argue that only the pauper-to-king life can be told as a redemption story and that it is good for you to live a redemption story. This paper calls that explanation into question and proposes an alternative: upward-trending lives reveal growth. I argue that growth is a (...) valuable feature of a life, that redemption is not, and that growth explains intuitions cited in favor of redemption. (shrink)

Recent scholarship has shown Nietzsche to offer an original and insightful moral psychology centering on a motivational feature he calls ‘will to power.’ In many places, though, Nietzsche presents will to power differently, as the ‘essence of life,’ an account of ‘organic function,’ even offering it as a correction to physiologists. This paper clarifies the scope and purpose of will to power by identifying the historical physiological view at which Nietzsche directs his criticisms and by identifying his purpose in doing (...) so. Nietzsche’s criticism, it is argued, is a widespread and pre-Darwinian description of the basic dispositions of organisms and their internal processes. The purpose of this criticism is to undermine the efforts of Herbert Spencer and Arthur Schopenhauer to derive moral-psychological insights from that description. The paper concludes that Nietzsche’s proposal to conceive of ‘organic function’ in terms of will to power is of little import for his moral psychology besides clearing away competing views. (shrink)

While “green marketing” has emerged as powerful competitive force, many markets lack clear institutional standards or knowledgeable customers to allow firms committed to sustainable practices to differentiate themselves from opportunistic, green-washing competitors. Within these contexts we propose a firm-level lens based on authentic firm reputation as an important, yet poorly understood, competitive force. Drawing on interview data from the architectural design services context we identify the elements that firms use to communicate their own authenticity, as well as discourage green-washing behavior (...) of peers, and present these elements as the “Diamond” model of authentic green marketing, consisting of: The ability to appear above commercial considerations; The ability to frame production methods as craft; The use of corporate visual identity; and An organization's social network of stakeholders. We conclude by discussing the generalizability and implications of our framework for practitioners as well as opportunities for future research. (shrink)

Nietzsche argues in the Genealogy of Morality (GM) that key aspects of modern European morality arose as “cures” for widespread human sickness but are ultimately making us sicker (“poisoning” us). This article provides a systematic overview of how Nietzsche believes morality has functioned as a cure and poison for European humanity. Drawing on my own previous work on Nietzsche’s concept of health, I sketch an overview of the (1) sicknesses, (2) treatments, and (3) pathogeneses discussed in each of the three (...) treatises in terms of a single (and plausible) concept of health. The result is a systematic interpretive overview of the core polemical argument in GM. (shrink)

In this article, I explore the impact of disability on one of life’s goods: achievement. Contra Campbell, Nyholm, and Walter, I argue that construing the magnitude of achievements in terms of subjective effort trivializes what it means to achieve. This poses a problem for the authors’ argument that disability, in general, does not reduce access to this good. I draw on an alternative construal of achievement that I have proposed elsewhere in order to show that, indeed, many disabilities do not (...) restrict access to achievement. I defend this argument against an objection that it problematically relativizes the achievements of persons with disability, and I close with general lessons for future work. (shrink)

ABSTRACT In this article, the author offers a reconstruction and criticism of Brian Leiter's interpretation of Nietzsche's criticism of conventional morality in Nietzsche on Morality. Leiter's interpretation is said to falter because it attributes to Nietzsche an implausible combination of positions. First, Nietzsche is said to be a value antirealist. But he is also said to defer to the value of the flourishing of his audience, who are limited to a certain subset of “higher” humans. The author argues that, in (...) spite of Leiter's attempt to defend this view, he ultimately fails to explain how Nietzsche can be confident in the normative force of the higher humans' flourishing and, so, his criticism of morality. Since the author takes the problems of Leiter's reading to bear on a prevalent general reading of Nietzsche, the author concludes with a brief sketch of a plausible alternative. (shrink)

There is broad agreement in aesthetics that some artworks are greater than others despite bearing equivalent (or lesser) aesthetic value. One explanation of this difference in artistic value is that creation of the greater artwork represents a greater achievement. The aim of this article is to refine this explanation and to defend it against recent criticisms. First, I present a prima facie case in favor of the achievement explanation. Second, I draw on the history of photography to motivate three objections (...) to it: namely, that it wrongly excludes (1) lucky, (2) easy, and (3) failed creations from being artistically great. Third, I present my refined version of the achievement explanation and show how it avoids these objections. On my view, an artistic achievement consists in creating a work it would have been especially hard for comparable artists to create. Finally, I raise and address several additional objections. In responding to these objections, I argue, among other things, that my explanation of artistic value enhances our understanding of good-bad art: specifically, it allows us to see how good-bad art is artistically great despite being aesthetically flawed. (shrink)

Nurse Ethicists bring a unique perspective to clinical ethics consultation. This perspective provides an appreciation of ethical tensions that will exist beyond the consult question into the moral space of patient care. These tensions exist even when an ethically preferable plan of action is identified. Ethically appropriate courses of action can still lead to moral dilemmas for others. The nurse ethicist provides a lens well suited to identify and respond to these dilemmas. The nurse–patient relationship is the ethical foundation of (...) nursing practice and this relational ontology is well suited to addressing ethical dilemmas that exist prior to and beyond the initial consult question. This paper will describe one nurse ethicist’s phronetic and pragmatic approach to a clinical ethics consult elucidated through feminist ethics and systems thinking. This paper will describe the theoretical basis for this method, present a case, and describe how this consultation approach provides a rich analysis based around relationships and responsibilities that also highlights the important ethical tensions within the social structure that exists around the patient and continue after the consult question is answered. (shrink)

The neonatologist was describing the dire situation, the complexity of the fetus's anomalies, and the options—comfort care, some resuscitation—and finished by saying, “We would not recommend ECMO …” “We would not recommend” is a curious phrase. There is something ambiguous, very nebulous about it, something passive, noncommittal, maybe even deflective. As a bioethics researcher, I wondered how this phrase is interpreted, how it influences parents' moral deliberation over their options.

Navigating tragic circumstances in pediatrics requires consideration of parental grief responses. We meet parents where they are, not where we might want them to be. Different parents grieve differ...

Caruso Brown brings forward an argument that clinicians and ethicists have a duty to consider decision-makers marginalized by hierarchical structures. The author presents a pragmatic approac...

Mammalian AMP‐activated protein kinase is the central component of a protein kinase cascade which inactivates three key enzymes involved in the synthesis or release of free fatty acids and cholesterol inside the cell. The kinase cascade is activated by elevation of AMP, and perhaps also by fatty acid and cholesterol metabolites. The system may fulfil a protective function, preventing damage caused by depletion of ATP or excessive intracellular release of free lipids, a type of stress response. Recent evidence suggests that (...) it may have been in existence for at least a billion years, since a very similar protein kinase cascade is present in higher plants. This system therefore represents an early eukaryotic protein kinase cascade, which is unique in that it is regulated by intracellular metabolites rather than extracellular signals or cell cycle events. (shrink)

The RecQ family of DNA helicases have been shown to be important for the maintenance of genomic integrity in all organisms analysed to date. In human cells, representatives of this family include the proteins defective in the cancer predisposition disorder Bloom's syndrome and the premature ageing condition, Werner's syndrome. Several pieces of evidence suggest that RecQ family helicases form associations with one or more of the cellular topoisomerases, and together these heteromeric complexes manipulate DNA structure to effect efficient DNA replication, (...) genetic recombination, or both. Here, we propose that RecQ helicases are required for ensuring that structural abnormalities arising during replication, such as at sites where replication forks encounter DNA lesions, are corrected with high fidelity. In mutants defective in these proteins, not only is replication abnormal, but cells display aberrant responses to DNA-damaging agents or inhibitors of DNA synthesis. We suggest that RecQ helicases may be important for the integration of cellular responses to these insults, such as by linking cell cycle checkpoint responses to recombinational repair. BioEssays 21:286–294, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

The DNA of all species is constantly under threat from both endogenous and exogenous factors, which damage its chemical structure. Probably the most common lesion that arises in cellular DNA is the loss of a base to generate an abasic site, which is usually referred to as an apurinic or apyrimidinic (AP) site. Since these lesions are potentially both cytotoxic and mutagenic, cells of all organisms express dedicated repair enzymes, termed AP endonucleases, to counteract their damaging effects. Indeed, many organisms (...) consider it necessary to express two or more of these lesion‐specific endonucleases, underscoring the requirement that exists to remove AP sites for the maintenance of genome integrity and cell viability. Most AP endonucleases are very versatile enzymes, capable of performing numerous additional repair roles. In this article, we review the AP endonuclease class of repair enzymes, with emphasis on the evolutionary conservation of structural features, not only between prokaryotic and eukaryotic homologues, but also between these enzymes and the RNase H domain of one class of reverse transcriptase. (shrink)