In a number of membrane-bound viruses, ion channels are formed by integral membrane proteins. These channel proteins include M2 from influenza A, NB from influenza B, and, possibly, Vpu from HIV-1. M2 is important in facilitating uncoating of the influenza A viral genome and is the target of amantadine, an anti-influenza drug. The biological roles of NB and Vpu are less certain. In all cases, the protein contains a single transmembrane α-helix close to its N-terminus. Channels can be formed by (...) homo-oligomerization of these proteins, yielding bundles of transmembrane helices that span the membrane and surround a central ion-permeable pore. Molecular modeling may be used to integrate and interpret available experimental data concerning the structure of such transmembrane pores. This has proved successful for the M2 channel domain, where two independently derived models are in agreement with one another, and with solid-state nuclear magnetic resonance (NMR) data. Simulations based on channel models may yield insights into possible ion conduction and selectivity mechanisms. BioEssays 20:992–1000, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

Plato's Euthyrphro, Apology, andCrito portray Socrates' words and deeds during his trial for disbelieving in the Gods of Athens and corrupting the Athenian youth, and constitute a defense of the man Socrates and of his way of life, the philosophic life. The twelve essays in the volume, written by leading classical philosophers, investigate various aspects of these works of Plato, including the significance of Plato's characters, Socrates's revolutionary religious ideas, and the relationship between historical events and Plato's texts.

Professor Gostin is a leading authority on health law, whose writing and teaching are among the most authoritative in the United States, as exemplified by his recent work, Public Health Law: Power, Duty, Restraint. Gostin's article in this issue of the Journal of Law, Medicine & Ethics pays homage to Jonathan Mann by expressing the debt he feels toward this extraordinary doctor and public health official with whom he had collaborated on several projects.As many will remember, Mann held high-level positions (...) at the Centers for Disease Control and worked on AIDS research in Central Africa before setting up the World Health Organization's Global Programme on AIDS, which he ran from 1986 to 1990. Thanks to his profound commitment and consummate communication skills, he achieved the unprecedented feat of raising the budget within two years to almost $100 million from the initial set-up of “himself, a secretary, and one typewriter,” as described by Daniel Tarantola. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Russell's leviathan by Mark S. Lippincott 1. INTRODUCTION BERTRAND RUSSELL'S POLITICAL thought underwent several metamorphoses in his nearly seventy years of political activism and writing. Indeed, many commentators on Russell take this as the overarching attribute ofhis politics. Alan Ryan writes that "Russell's career defies summary analysis; his life was much too long and his activities too various. His philosophical allegiances were no more stable than his emotional (...) allegiances, and his political allegiances no more stable than either."1 Likewise, Benjamin Barber suggests that "Russell had to contend with staying alive; and by the time he was ninety, consistency must have seemed to him less like the hobgoblin of little minds than the hallmark Of a short life."2 Ryan, Barber and others come to different conclusions about Russell's engagements with pacifism, anarcho-syndicalism, socialism and liberalism, but their efforts, taken collectively, signal a growing appreciation for the fluidity of Russell's politics. This essay treats the diversity of Russell's "political allegiances" as a first step 1 Alan Ryan, Bertrand Russell: a Political Life (London: Allen Lane The Penguin Press, 1988), p. l. 2 Benjamin R. Barber, "Solipsistic Politics: Bertrand Russell and Empiricist Liberalism", in his The Conquest ofPolitics: Liberal Philosophy in Democratic Times (Princeton: Princeton U. P., 1988), p. 25. Russell's leviathan 7 toward a new understanding of his political thought. Yet, unlike so much commentary on Russell, the search for the overarching concept or unifying theme is eschewed. The core premise of the argument is that to understand the political Russell, it is necessary to suspend the urge to unify. What is crucial is an openness to the extraordinary variety and range of his political interests and reflections. Once this step is taken, it becomes possible to uncover the degree to which Russell's eclectic activism is reflected in his approach to political theory. It becomes possible to see that his statements on a particular political issue are embedded with concepts selected from various sources within the western tradition ofpolitical discourse. In addition, this approach highlights the conceptual background of some of Russell's more contentious political statements which seem so characteristically out of character. The issue selected for this essay arises from one of the most controversial and least understood acts in Russell's life. It concerns his public statements following World War II that the United States might do well to use its monopoly of atomic bombs to force the Soviet Union into abandoning the development of its own atomic weapons. Past attempts to explain this episode range from cursory denials and dismissals of its importance, to assertions that it was the step-child of Russell's Russophobia.3 If one examines these state3 The argument for threatening the Soviet Union into renouncing nuclear weapons is advanced by Russell in several public statements: "The Bomb and Civilization", Forward, 29 Sept. 1945; "Humanity's Last Chance", Cavalcade, 20 Oct. 1945; speech in the House of Lords, Hansard,_'2,~Nov. 1945; "The Atomic Bomb and the Prevention of War", Polemic, July-Aug. 1946; speech in the House of Lords, Hansard, 30 April 1947; "Still Time for Good Sense", '47 Magazine ofthe Year, Nov. 1947; "International Government", The New Commonwealth, Jan. 1948. Ronald Clark provides an important guide to Russell's statements during this period in Vie Life of Bertrand Russell (London : CapelWeidenfeld & Nicolson, 1975), but he does not examine the philosophical background. Alan Ryan comes closest to seeing Russell's theoretical link with Hobbes, but he leaves it as a passing remark about Russell's attitude towards world government during the First World War: "It is as if Russell had read Hobbes's Leviathan and been carried away by Hobbes's argument that the state of nature and the war of all against all was so dreadful that any rational man would fly to absolute monarchy for protection. Russell generalizes Hobbes's argument to the international sphere, but it fails to ask how men who get themselves into a 'war of all against all' can be expected to get themselves out again, and fails to show how they have done 8 Russell summer 1990 ments with an eye to Russell's... (shrink)

Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

© 2017. The American Astronomical Society. All rights reserved.We present new observations of the low-mass companion to HD 984 taken with the Gemini Planet Imager as a part of the GPI Exoplanet Survey campaign. Images of HD 984 B were obtained in the J and H bands. Combined with archival epochs from 2012 and 2014, we fit the first orbit to the companion to find an 18 au orbit with a 68% confidence interval between 14 and 28 au, an eccentricity (...) of 0.18 with a 68% confidence interval between 0.05 and 0.47, and an inclination of 119°with a 68% confidence interval between 114°and 125°. To address the considerable spectral covariance in both spectra, we present a method of splitting the spectra into low and high frequencies to analyze the spectral structure at different spatial frequencies with the proper spectral noise correlation. Using the split spectra, we compare them to known spectral types using field brown dwarf and low-mass star spectra and find a best-fit match of a field gravity M6.5 ±1.5 spectral type with a corresponding temperature of K. Photometry of the companion yields a luminosity of log=2.88 ± 0.07 dex with DUSTY models. Mass estimates, again from DUSTY models, find an age-dependent mass of 34 ±1 to 95 ±4 M Jup. These results are consistent with previous measurements of the object. (shrink)

Herein I address and extend the sparse literature on deception in sports, specifically, Kathleen Pearson’s Deception, Sportsmanship, and Ethics and Mark J. Hamilton’s There’s No Lying in Baseball. On a Kantian foundation, I argue that attempts to deceive officials, such as framing pitches in baseball, are morally unacceptable because they necessarily regard others as incompetent and as a mere means to one’s own self-interested ends. More dramatically I argue, contrary to Pearson and Hamilton, that some forms of competitor-to-competitor deception (...) are similarly unacceptable. Specifically, I offer a ‘principle of caustic deceit’ according to which any strategic deception that divorces a game from its constitutive skills is morally untoward and ought to be met with negative social pressure at least, and/or legislated out of existence. The problem with these forms of strategic deception is that they treat one’s opponents, again in the Kantian sense, as a mere means to one’s own self-interested ends. (shrink)

Dubourg and Baumard's paper takes a different, and fruitful, approach to the study of imaginary worlds than what is usually found in Media Studies, but omits certain circumstances and influences that shaped their history; this article argues that psychological or behavioral factors are not enough to explain the growth of imaginary worlds, even as they may be important influences.

Where should one look to find a medieval theology of Biblical inspiration? Some scholars believe it does not exist. Denis Farkasfalvy takes to task neo-scholastics primarily of the period between Vatican Councils I and II for falsifying the theology: “Thomists and neo-Thomists like to use Thomas’s thought on prophecy for developing a scholastic theology of biblical inspiration,” but although “theological textbooks of the early twentieth century often pretended to be articulating St. Thomas’s actual teaching … Aquinas never asked the question (...) of how divine and human actions had jointly produced the Bible.”1 Farkasfalvy’s analysis applies equally to Albert.A comprehensive rebuttal of his claim lies beyond the scope... (shrink)

Memory for spatial location is typically biased, with errors trending toward the center of a surrounding region. According to the category adjustment model, this bias reflects the optimal, Bayesian combination of fine-grained and categorical representations of a location. However, there is disagreement about whether categories are malleable. For instance, can categories be redefined based on expert-level conceptual knowledge? Furthermore, if expert knowledge is used, does it dominate other information sources, or is it used adaptively so as to minimize overall error, (...) as predicted by a Bayesian framework? We address these questions using images of geological interest. The participants were experts in structural geology, organic chemistry, or English literature. Our data indicate that expertise-based categories influence estimates of location memory—particularly when these categories better constrain errors than alternative categories. Results are discussed with respect to the CAM. (shrink)

In a vivid re-creation of late sixteenth-century Flemish intellectual life, Mark Morford explores the intertwined careers of one of the period's most influential thinkers and one of its most original artists: Justus Lipsius and Peter Paul Rubens. He investigates the scholarship of Lipsius (1547-1606), whose revival of Roman Stoicism guided his contemporaries during the revolt of the Netherlands from the rule of Spain and whose teaching prepared future leaders in church and state. Maintaining that Lipsius' thought reached Peter Paul (...) Rubens through his brother, Philip Rubens, Morford analyzes the artist's use of Stoic philosophical and political allegory, beginning with his painting The Four Philosophers. This book discusses the revival of Stoicism in northern Europe, focusing on Lipsius' editions of Tacitus and Seneca, his widely read handbooks on constancy and politics, and his interaction with leading scholars and public figures. As his letters reveal, Lipsius was inconsistent in his life and unsuccessful in reconciling Stoicism with Catholic doctrine; Rubens, although at first sympathetic to the doctrines of Lipsius, is shown to have later transcended their limitations. (shrink)

There is increasing evidence that dynamic changes to chromatin, chromosomes and nuclear architecture are regulated by RNA signalling. Although the precise molecular mechanisms are not well understood, they appear to involve the differential recruitment of a hierarchy of generic chromatin modifying complexes and DNA methyltransferases to specific loci by RNAs during differentiation and development. A significant fraction of the genome-wide transcription of non-protein coding RNAs may be involved in this process, comprising a previously hidden layer of intermediary genetic information that (...) underpins developmental ontogeny and the differences between species, ecotypes and individuals. It is also evident that RNA editing is a primary means by which hardwired genetic information in animals can be altered by environmental signals, especially in the brain, indicating a dynamic RNA-mediated interplay between the transcriptome, the environment and the epigenome. Moreover, RNA-directed regulatory processes may also transfer epigenetic information not only within cells but also between cells and organ systems, as well as across generations. (shrink)

“Just for the record, however: I don't hate Communists.” So wrote Arcadius Rudolph Lang Gurland to his longtime friend, colleague, and collaborator Otto Kirchheimer in 1958.1 Behind this straightforward statement lay over thirty years of Gurland's experience as a passionate scholar, spokesperson, and advocate of that most dialectical of the many forms of socialist politics, revolutionary social democracy. Throughout his peripatetic life of near-constant exile in Russia, Germany, France, and the United States as student, journalist, theoretician, researcher, writer, teacher, and (...) translator in the service of political organizations, newspapers, research institutions, universities, governments, publishers, and his own political and scholarly.. (shrink)

This Handbook provides an intellectually rigorous and accessible overview of the relationship between natural law and human rights. It fills a crucial gap in the literature with leading scholarship on the importance of natural law as a philosophical foundation for human rights and its significance for contemporary debates. The themes covered include: the role of natural law thought in the history of human rights; human rights scepticism; the different notions of 'subjective right'; the various foundations for human rights within natural (...) law ethics; the relationship between natural law and human rights in religious traditions; the idea of human dignity; the relation between human rights, political community and law; human rights interpretation; and tensions between human rights law and natural law ethics. This Handbook is an ideal introduction to natural law perspectives on human rights, while also offering a concise summary of scholarly developments in the field. (shrink)

Strategies for disclosing investigators' financial interests to potential research participants have been adopted by many research institutions. However, little is known about how decisions are made regarding disclosures of financial interests to potential research participants, including what is disclosed and the rationale for making these determinations. We sought to understand the attitudes, beliefs, and practices of institutional review board chairs, conflict of interest committee chairs, and investigators regarding disclosure of financial interests to potential research participants. Several themes emerged, including general (...) attitudes toward conflicts of interest, circumstances in which financial interests should be disclosed, rationales and benefits of disclosure, what should be disclosed, negative effects of and barriers to disclosure, and timing and presentation of disclosure. Respondents cited several rationales for disclosure, including enabling informed decision making, promoting trust in researchers and research institutions, and reducing legal liability. There was general agreement that disclosure should happen early in the consent process. Respondents disagreed about whether to disclose the amounts of particular financial interests. Clarifying the goals of disclosure and understanding how potential research participants use the information will be critical in efforts to ensure the integrity of clinical research and to protect the rights and interests of participants. (shrink)

This paper argues that the type of conscience claims made in last decade’s spate of cases involving pharmacists’ objections to filling birth control prescriptions and cases such as Ms. Means and Mercy Health Partners of Michigan, and even the Affordable Care Act and the Little Sisters of the Poor, as different as they appear to be from each other, share a common element that ties them together and makes them fundamentally different in kind from traditional claims of conscience about which (...) a practical consensus emerged in the 1980s and 1990s. This difference in kind is profoundly significant; so much so, we contend, that it puts them at odds with the normative basis for protecting conscience claims in United States health care settings in the first place, making them illegitimate. Finally, we argue that, given the illegitimacy of these contemporary claims of conscience, physicians and other health professionals must honor their well-established standing obligations to provide informed consent and refer or transfer care even if the service requested or needed is at odds with their own core moral beliefs—a requirement that is in line with the aforementioned practical consensus on traditional claims of conscience. (shrink)

Mark Morford provides a lively, succinct, and comprehensive survey of the philosophers of the Roman World, from Cato the Censor in 155 BCE to the death of Marcus Aurelius in 180 CE. These men were asking philosophical questions whose answers had practical effects on people's lives in antiquity--and still do today--yet this is an era of philosophy somewhat neglected in recent decades. Morford puts this right by discussing the writings and ideas of numerous famous and lesser-known figures. Using extensive (...) and fully-translated quotations from their works, he illuminates each of the philosopher's meanings within the historical, political, and cultural contexts of their day. This book serves as the ideal introduction to the newcomer to Roman philosophy. (shrink)

In this article I develop a model of theoretical understanding in science. This is a philosophical theory that specifies the conditions that are both necessary and sufficient for a scientist to satisfy the construction ‘S understands theory T ’. I first consider how this construction is preferable to others, then build a model of the requisite conditions on the basis of examples from elementary physics. I then show how this model of theoretical understanding can be made philosophically robust and provide (...) a more sophisticated account than we see from models of a similar kind developed by those working in the psychology of physics and artificial intelligence. 1 Introduction2 The Explicandum/Analysandum3 Analysis of ‘S understands T’ 4 The Inferential Model4.1 Which problems are we talking about?4.2 Does the solution have to be true?4.3 Does each cycle have to be correct for S to understand T?4.4 What is problem-solving reliability?4.5 Does every specific inference of a cycle have to be correct?4.6 Does each inference have to use a principle that is part of the theory?5 Theoretical Understanding and Conceptual Expertise: Empirical Considerations6 Conclusion: Inferential Model of Scientific Understanding and Our Traditional Problems. (shrink)

Investigator and institutional financial conflicts of interest have raised concerns about both the integrity of clinical research and protecting the rights and welfare of research participants. In response, professional groups and governmental bodies have issued guidance for managing conflicts of interest to minimize their potential untoward effects. Although a variety of approaches have been offered, a common protection is to disclose financial interests in research to potential research participants as part of the recruitment and informed consent process. This approach reinforces (...) a basic norm of candor, ideally allowing potential research participants to evaluate whether financial interests should affect their decision to participate in research. Disclosure to potential research participants is viewed as an alternative to having regulators or research institutions limit or prohibit all financial interests in research, assuming that not all such interests are unacceptable. (shrink)

We are developing the Neurological Disease Ontology (ND) to provide a framework to enable representation of aspects of neurological diseases that are relevant to their treatment and study. ND is a representational tool that addresses the need for unambiguous annotation, storage, and retrieval of data associated with the treatment and study of neurological diseases. ND is being developed in compliance with the Open Biomedical Ontology Foundry principles and builds upon the paradigm established by the Ontology for General Medical Science (OGMS) (...) for the representation of entities in the domain of disease and medical practice. Initial applications of ND will include the annotation and analysis of large data sets and patient records for Alzheimer’s disease, multiple sclerosis, and stroke. (shrink)

From his earliest work on personal identity to his last on the value of truthfulness, the ideas and arguments of Bernard Williams - in the metaphysics of personhood, in the history of philosophy, but especially in ethics and moral psychology - have proved sometimes controversial, often influential, and always worth studying. This book provides a comprehensive account of Williams's many significant contributions to contemporary philosophy. Topics include personal identity, various critiques of moral theory, practical reasoning and moral motivation, truth and (...) objectivity, and the relevance of ancient Greece to modern life. It not only positions Williams among these important philosophical topics, but also with regard to the views of other philosophers, including prominent forerunners such as Hume and Nietzsche and contemporary thinkers such as, Nagel, McDowell, MacIntyre and Taylor. The fragmentary nature of Williams's work is addressed and recurring themes and connections within his work are brought to light. (shrink)

There are several models of the use of geometric and feature cues in reorientation. The adaptive combination approach posits that people integrate cues with weights that depend on cue salience and learning, or, when discrepancies are large, they choose between cues based on these variables. In a new paradigm designed to evaluate integration and choice, disoriented participants attempted to return to a heading direction, in a trapezoidal enclosure in which feature and geometric cues both unambiguously specified a heading, but later (...) the feature was moved. With discrepancies greater than 90 degrees, participants choose geometry. With smaller discrepancies, integration appeared in three of five situations; otherwise, participants used geometry alone. Variation depended on direction of feature movement and whether the nearest corner was acute or obtuse. The results have implications for contrasting adaptive combination and modularity theory, and for future research, offering a new paradigm for reorientation research, and for testing cue integration more broadly. (shrink)

The medium surrounding cells either in culture or in tissues contains a chemical mix varying with cell state. As solutes move in and out of the cytoplasmic compartment they set up characteristic signatures in the cellular boundary layers. These layers are complex physical and chemical environments the profiles of which reflect cell physiology and provide conduits for intercellular messaging. Here we review some of the most relevant characteristics of the extracellular/intercellular space. Our initial focus is primarily on cultured cells but (...) we extend our consideration to the far more complex environment of tissues, and discuss how chemical signatures in the boundary layer can or may affect cell function. Critical to the entire essay are the methods used, or being developed, to monitor chemical profiles in the boundary layers. We review recent developments in ultramicro electrochemical sensors and tailored optical reporters suitable for the task in hand. (shrink)

As John Henry Newman reflected on 'The Idea of a University' more than a century and a half ago, Bradley C. S. Watson brings together some of the nation's most eminent thinkers on higher education to reflect on the nature and purposes of the American university today. Their mordant reflections paint a picture of the American university in crisis. This book is essential reading for thoughtful citizens, scholars, and educational policymakers.

A collection of personal narratives and essays, Living Professionalism is designed to help medical students and residents understand and internalize various aspects of professionalism. These essays are meant for personal reflection and above all, for thoughtful discussion with mentors, with peers, with others throughout the health care provider community who care about acting professionally.

An extended period of childhood and juvenility is a distinctive aspect of human life history. This stage appears to be important for learning cultural, social, and ecological skills that help prepare the child for the adult socio-competitive environment. The unusual pattern of adrenarche in humans (and chimpanzees) may facilitate adaptive modification of the neurobiological mechanisms that underpin reproductive strategies. Longitudinal monitoring of DHEA/S in naturalistic context could provide important new insights into these aspects of child development.

Psychiatry is rapidly adopting digital phenotyping and artificial intelligence/machine learning tools to study mental illness based on tracking participants’ locations, online activity, phone and text message usage, heart rate, sleep, physical activity, and more. Existing ethical frameworks for return of individual research results (IRRs) are inadequate to guide researchers for when, if, and how to return this unprecedented number of potentially sensitive results about each participant’s real-world behavior. To address this gap, we convened an interdisciplinary expert working group, supported by (...) a National Institute of Mental Health grant. Building on established guidelines and the emerging norm of returning results in participant-centered research, we present a novel framework specific to the ethical, legal, and social implications of returning IRRs in digital phenotyping research. Our framework offers researchers, clinicians, and Institutional Review Boards (IRBs) urgently needed guidance, and the principles developed here in the context of psychiatry will be readily adaptable to other therapeutic areas. (shrink)

In “Bioethics and the Whole: Pluralism, Consensus, and the Transmutation of Bioethical Methods into Gold,” Patricia Martin identifies themes common to three emerging approaches to clinical bioethics--clinical pragmatism, ethics facilitation, and mediation-in order to develop an “ethical consensus method” that can serve as a “practical, step-by-step guide” for decision making She is to be applauded both for her identification of themes common to these three approaches and for her contribution to what we hope will be a growing literature on practical (...) methods for problem solving in clinical bioethics that take seriously the ideal of consensus. After a few preliminary remarks concerning Martin's working model, we focus the majority of our commentary on the notion of “consensus,” which is at the heart of her “ethical consensus method,” and the three approaches from which it is drawn. (shrink)

In “Consensus, Clinical Decision Making, and Unsettled Cases,” David M. Adams and William J. Winslade make multiple references to both editions of the American Society of Bioethics and Humanities (ASBH) Core Competencies for Healthcare Ethics Consultation in their discussion of two assumptions that are supposed to be at the heart of the facilitated consensus model’s inability to handle unsettled cases; that is, that:1. Consultants “should maintain a kind of moral impartiality or neutrality throughout the process,” “explicitly condemn[ing] anything resembling a (...) substantive ‘ethics’ recommendation,” and2. “What counts as the proper set of allowable options among which the parties are to deliberate will itself always be clearly discernible.”Herein, I argue that neither of these assumptions is required by ASBH’s ethics facilitation approach. I then conclude by suggesting that, despite their fundamentally mistaken interpretation of the ASBH approach—perhaps even because of it—Adams and Winslade have made two important contributions to the ethics consultation literature. (shrink)

Clinical ethics committees, with their typical threefold function of education, policy formation, and consultation, are present in nearly all U.S. hospitals today, and they are increasingly common in other healthcare settings such as long-term care and even home care. Ethics committees are at least as prevalent in Canadian hospitals as they are in U.S. hospitals, and their presence is growing in Europe, much of Asia, and Central and South America. Although ethics committees serve a variety of needs, their ultimate goal (...) ought to be to promote ethical practices or, in other words, to engender the integration of ethics into the life of the medical center. Of the three primary functions of ethics committees, ethics consultation has historically been the most controversial and problematic, and consult services in many healthcare institutions have struggled to thrive. (shrink)

On September 8, 2015, the Department of Health and Human Services issued a Notice of Proposed Rule Making to revise the Federal Policy for the Protection of Human Subjects, widely known as the “Common Rule.” The NPRM proposes several changes to the current system, including a dramatic shift in the approach to secondary research using biospecimens and data. Under the current rules, it is relatively easy to use biospecimens and data for secondary research. This approach systematically facilitates secondary research with (...) biospecimens and data, maximizing the capacity for substantial public benefit. However, it has been criticized as insufficiently protective of the privacy and autonomy interests of biospecimen and data sources. Thus, the NPRM proposes a more restrictive regime, although more so for biospecimens than data. Both the status quo and the NPRM's proposal are critically flawed. (shrink)

This article extends recent efforts to investigate Nietzsche through the lens of Bernard Williams and Williams through the lens of Nietzsche by focusing on their respective conceptions of, and attitudes toward, pessimism. Specifically, the article investigates whether Williams should be regarded as endorsing or manifesting tragic or Dionysian forms of pessimism, which Nietzsche valorizes under the term “pessimism of strength,” or whether he is better associated with the Schopenhauerian or romantic pessimism, or even the Socratic optimism, that Nietzsche rejects. The (...) answer is held to turn on the interpretation of Williams's obscure notion of “confidence.”. (shrink)

Described as one of the two fathers of medical law, Professor Peter Skegg has been a leading figure in the study of law and medicine. Over a 46 year academic career at the University of Auckland, University of Oxford, and the University of Otago, Professor Skegg has helped develop the field of medical law into a burgeoning academic discipline and has provided intellectual guardianship for the practice of law and medicine. This collection brings together contemporaries, colleagues, and former students of (...) Professor Skegg to celebrate his enduring contribution to the study of medical law. This edited collection contains twelve essays written by a range of internationally recognised medical lawyers. The topics cover the regulation of medical practitioners, consent, rights in bodily material, euthanasia, compensation and ethical approval for medical research, treatment orders for mental health conditions, and surrogacy laws. Whilst some of the essays return to territory that has been initially surveyed by Peter s research and analysis, others touch upon some wider medical law topics, illustrating Peter s lasting contribution to medical law as well as mapping out some of the new frontiers for the discipline of medical law. Academics, students and practitioners, from a range of jurisdictions, who are interested in how the law governs the provision of healthcare will benefit reading the various essays contained here. In addition, anyone who has had the good fortune of working with, or learning from, Professor Skegg will also enjoy the opportunity to return to the field of study that he founded. (shrink)

The crisis in donor organ and tissue supply is one of the most difficult challenges for transplant today. New policy initiatives, such as the driver's license option and requiredrequest, have been implemented in many states, with other initiatives, such as mandatedchoice and presumedconsent, proposed in the hopes of ameliorating this crisis. At the same time, traditional acquisition of organs from human cadavers has been augmented by living human donors, and nonheartbeating human donors, as well as experimental animal and artificial sources. (...) Despite these efforts, the crisis persists and is perhaps most tragic when it threatens the lives of children, driving parents to sometimes desperate measures. Herein, we address one very controversial step some parents have taken to obtain matching tissue or organs for their needy children—that is, having a child, in part, for the purpose of organ or tissue procurement. (shrink)

Presenilin‐1 (PS1) is thought to regulate cell differentiation and survival by modulating the Notch signaling pathway. Mutations in PS1 have been shown to cause early‐onset inherited forms of Alzheimer's disease (AD) by a gain‐of‐function mechanism that alters proteolytic processing of the amyloid precursor protein (APP) resulting in increased production of neurotoxic forms of amyloid β‐peptide. The present article considers a second pathogenic mode of action of PS1 mutations, a defect in cellular calcium signaling characterized by overfilling of endoplasmic reticulum (ER) (...) calcium stores and altered capacitive calcium entry; this abnormality may impair synaptic plasticity and sensitize neurons to apoptosis and excitotoxicity. The calcium signaling defect has also been documented in lymphocytes, suggesting a contribution of immune dysfunction to the pathogenesis of AD. A better understanding of the calcium signaling defect resulting from PS1 mutations may lead to the development of novel preventative and therapeutic strategies for disorders of the nervous and immune systems. BioEssays 23:733–744, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Genomic research results and incidental findings with health implications for a research participant are of potential interest not only to the participant, but also to the participant's family. Yet investigators lack guidance on return of results to relatives, including after the participant's death. In this paper, a national working group offers consensus analysis and recommendations, including an ethical framework to guide investigators in managing this challenging issue, before and after the participant's death.