The sporadic nature of Alzheimer's disease argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead during brain development predetermined the expression and regulation of the amyloid precursor protein and its amyloidogenic beta-amyloid product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 ] as well as their transcriptional regulator were elevated in aged (...) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Abeta staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD. (shrink)

The behavioral sciences have flourished by studying how traditional and/or rational behavior has been governed throughout most of human history by relatively well-informed individual and social learning. In the online age, however, social phenomena can occur with unprecedented scale and unpredictability, and individuals have access to social connections never before possible. Similarly, behavioral scientists now have access to “big data” sets – those from Twitter and Facebook, for example – that did not exist a few years ago. Studies of human (...) dynamics based on these data sets are novel and exciting but, if not placed in context, can foster the misconception that mass-scale online behavior is all we need to understand, for example, how humans make decisions. To overcome that misconception, we draw on the field of discrete-choice theory to create a multiscale comparative “map” that, like a principal-components representation, captures the essence of decision making along two axes: aneast–westdimension that represents the degree to which an agent makes a decision independently versus one that is socially influenced, and anorth–south dimensionthat represents the degree to which there is transparency in the payoffs and risks associated with the decisions agents make. We divide the map into quadrants, each of which features a signature behavioral pattern. When taken together, the map and its signatures provide an easily understood empirical framework for evaluating how modern collective behavior may be changing in the digital age, including whether behavior is becoming more individualistic, as people seek out exactly what they want, or more social, as people become more inextricably linked, even “herdlike,” in their decision making. We believe the map will lead to many new testable hypotheses concerning human behavior as well as to similar applications throughout the social sciences. (shrink)

The behavioral sciences have flourished by studying how traditional and/or rational behavior has been governed throughout most of human history by relatively well-informed individual and social learning. In the online age, however, social phenomena can occur with unprecedented scale and unpredictability, and individuals have access to social connections never before possible. Similarly, behavioral scientists now have access to “big data” sets – those from Twitter and Facebook, for example – that did not exist a few years ago. Studies of human (...) dynamics based on these data sets are novel and exciting but, if not placed in context, can foster the misconception that mass-scale online behavior is all we need to understand, for example, how humans make decisions. To overcome that misconception, we draw on the field of discrete-choice theory to create a multiscale comparative “map” that, like a principal-components representation, captures the essence of decision making along two axes: aneast–westdimension that represents the degree to which an agent makes a decision independently versus one that is socially influenced, and anorth–south dimensionthat represents the degree to which there is transparency in the payoffs and risks associated with the decisions agents make. We divide the map into quadrants, each of which features a signature behavioral pattern. When taken together, the map and its signatures provide an easily understood empirical framework for evaluating how modern collective behavior may be changing in the digital age, including whether behavior is becoming more individualistic, as people seek out exactly what they want, or more social, as people become more inextricably linked, even “herdlike,” in their decision making. We believe the map will lead to many new testable hypotheses concerning human behavior as well as to similar applications throughout the social sciences. (shrink)

Transplantation of vital organs has been premised ethically and legally on "the dead donor rule" (DDR)—the requirement that donors are determined to be dead before these organs are procured. Nevertheless, scholars have argued cogently that donors of vital organs, including those diagnosed as "brain dead" and those declared dead according to cardiopulmonary criteria, are not in fact dead at the time that vital organs are being procured. In this article, we challenge the normative rationale for the DDR by rejecting the (...) underlying premise that it is necessarily wrong for physicians to cause the death of patients and the claim that abandoning this rule would exploit vulnerable patients. We contend that it is ethical to procure vital organs from living patients sustained on life support prior to treatment withdrawal, provided that there is valid consent for both withdrawing treatment and organ donation. However, the conservatism of medical ethics and practical concerns make it doubtful that the DDR will be abandoned in the near future. This leaves the current practice of organ transplantation based on the "moral fiction" that donors are dead when vital organs are procured. (shrink)

If stem cell-based therapies are developed, we will likely confront a difficult problem of justice: for biological reasons alone, the new therapies might benefit only a limited range of patients. In fact, they might benefit primarily white Americans, thereby exacerbating long-standing differences in health and health care.

During the decades following the publication of Darwin's Origin of species in 1859, religious belief in England and in particular the Church of England experienced some of the most intense criticism in its history. The early 1860s saw the appearance of Lyell's Evidence of the antiquity of man , Tylor's research on the early history of mankind , Renan's Vie de Jésus , Pius IX's encyclical, Quanta cura, and the accompanying Syllabus errarum, John Henry Newman's Apologia , and Swinburne's notorious (...) Atalanta in Calydon ; it was in this period also that Arthur Stanley was appointed Dean of Westminster, and that Bills were introduced in Parliament to amend or repeal the ‘Test Acts’ as they affected universities. They were the years that witnessed Lyell present the case for geology at the British Association at Bath , the first meeting of the X-Club , and the award of the Royal Society's Copley Medal to Charles Darwin. These were the years in which, as Owen Chadwick has put it, ‘the controversy between “science” and “religion” took fire’. (shrink)

Alzheimer's disease is characterized by amyloid-beta peptide -loaded plaques in the brain. Abeta is a cleavage fragment of amyloid-beta protein precursor and over production of APP may lead to amyloidogenesis. The regulatory region of the APP gene contains consensus sites recognized by the transcription factor, specificity protein 1 , which has been shown to be required for the regulation of APP and Abeta. To understand the role of SP1 in APP biogenesis, herein we have characterized the relative distribution and localization (...) of SP1, APP, and Abeta in various brain regions of rodent and primate models using immunohistochemistry. We observed that overall distribution and cellular localization of SP1, APP, and Abeta are similar and neuronal in origin. Their distribution is abundant in various layers of neocortex, but restricted to the Purkinje cell layer of the cerebellum, and the pyramidal cell layer of hippocampus. These findings suggest that overproduction of Abeta in vivo may be associated with transcriptional pathways involving SP1 and the APP gene. (shrink)

In this article, drawing on the discursive psychology of Rom Harré, we show how mapping the exchange of words among people might disclose a complex reality; not merely that which farmers explicitly talk ‘about’ but the reality implicitly at stake within the communication. More specifically, we show how discourses involving modern farmers reveal an underlying placing in an abstract space, having sub-spaces defined by the life-orientation, sense of self and according self-positioning of modern people. In this way, we construct a (...) road map of a set of ‘individualities’ characterizing the life of modern farmers: an individuality of citizenship, an individuality of geographies and an individuality of experience. Consequently, farmers face the problem that this multiplicity of individuality prevents them from communicating, as we will call it, univocally in the public by contrast to the univocal voices of other established social groups. We will analyse the structure of that problem by viewing diverse relations between the authority and the authenticity of different partners in the conversation on land use. (shrink)

When firms face crisis, the instant and open channels of social media communication create a double-edged sword. While corporations can more quickly communicate with stakeholders, any missteps will have drastic and nearly immediate repercussions. What are the relationships among social media, subjective norms, attitudes, and intentions during corporate crisis? We explore this phenomenon via a study of a crisis faced by Lowe’s, an international home improvement store, and how current and potential customers reacted. By utilizing a structural equations model to (...) examine an integrated model of multiple constructs, we find that Facebook usage is associated with behavioral intent, perceptions of ethicality, and attitudes toward the organization. Counter intuitively, we find that an increase in participant Facebook usage is negatively related to felt subjective norms. Our findings indicate that beyond the traditional relationships examined by the Theory of Reasoned Action (e.g., norms, attitudes, and behavioral intent), that social media and subjective norms have a strong relationship with general attitudes and ethical attitudes toward an organization. (shrink)

Book Information The Morality of Nationalism. Edited by R. McKim and J. McMahan. Oxford University Press. New York. 1997. Pp. xii + 371. Paperback, $42.95.

In lieu of an abstract, here is a brief excerpt of the content:Principles and PragmatismR. Alta Charo (bio)Openly, privately, or implicitly, every public ethics committee struggles with its mandate. Is its job to identify a moral ideal?; a morally acceptable minimum that, realistically, could be adopted as policy?; or an optimal political compromise that can arguably meet ethical analysis? The answer appears to be different for each committee, depending upon its subject matter, its sponsoring political body, and the details of (...) its legal mandate. What is universal, however, is that even the most well-intentioned committee is likely to experience dissension over the interpretation of its task and that this dissension will often be played out in debates over particular policy recommendations.Ruth Macklin’s description of disagreement and moral integrity in the context of the Advisory Committee on Human Radiation Experiments demonstrates this phenomenon quite clearly (Macklin 1996). The epistemological debates concerning the evidence of past practices illuminate differing visions of the Committee’s mandate. For some it was to render moral judgment on past acts, without necessarily concluding that, if the acts were immoral, the individuals involved were themselves immoral. For others it was to use moral judgments to determine appropriate forms of restitution, thus balancing the reputational risks to past actors against the need for and feasibility of restitution to the victims. Still others appeared to focus on crafting specific political responses, and the historical data needed only be sufficient to bolster the policy recommendations.In this respect, the composition of any advisory committee becomes crucial. As fact-finders, committee members must determine the kind of evidence they will find persuasive. This determination, in turn, depends upon whether the committee sees itself primarily as (1) informational, in which case the standards employed by professional historians are probably the most appropriate, or (2) judgmental, in which case something closer to legal standards of proof might be better. The dilemma is not limited to committees looking at history; those rendering advice on science policy need to determine if they will use standards of proof prevalent in the scientific community (consensus following peer review) or the public (scientific consensus coupled with credibility of the scientific community as a whole). [End Page 319]When a committee is asked to base its judgments on ethical analysis, the conflicts only deepen. The “ethics” of policy recommendations are invariably balanced against the desire to see one’s work yield a concrete political response, the perception of political constraints on implementing an ethically “ideal” solution, and the subtle pressures exerted by the sponsoring political body to respond to the specific committee mandate, which was written with the needs of the sponsoring body in mind, not the needs of a wide-ranging ethics discussion.Another complication arises because ethics committees derive their credibility from the perception that moral truth is discoverable and unassailable. To horse trade among these moral truths undermines the credibility of their entire endeavor and can render bioethics advisory committees not only ineffective but even offensive. After all, if a moral truth exists, how ethical is it for “ethicists” to abandon it in the name of strategic concerns? If, on the other hand, no moral truth exists, then by what right do these “ethics” committees claim persuasive authority beyond that of any citizen advisory committee?This is a deep dilemma that relates to the discipline of bioethics itself. Lacking a core methodology or doctrine, bioethics has yet to justify itself to either its proponents or to the public. Bioethics scholars acknowledge that there are a variety of theories drawn from moral philosophy that could be used to guide the resolution of dilemmas that arise in the context of medical care and biomedical research. Such theories include utilitarianism, deontology, teleology, virtue theory, and justice theory, with no one theory being universally adopted by bioethics scholars and no one methodology being available to resolve conflicts among their respective conclusions. While deductivism is the predominant analytical style in the field, “[t]he central difficulty with deductivism is that there is no single comprehensive moral theory, nor even theories or principles of more limited scope, which is agreed to be true or correct” from which defensible conclusions will flow (Brock 1995).But if public ethics bodies cannot... (shrink)

When this invaluable account of ‘one of the most successful of all publishers and printers of nineteenth- and twentieth-century science’ was first issued in 1984, it began with a survey of the underdeveloped literature on the history of scientific periodicals, and more generally of science publishing. A decade and a half later, in this considerably expanded second edition— issued to celebrate the bicentenary of the launch of the Philosophical Magazine in 1798—the authors had only a couple of extra titles to (...) add. Since then, a number of important works have addressed this theme, but the field remains wide open.1 Most of the key technicians of print—the publishers, printers, and engravers—who were responsible for the production of scientific books in nineteenth-century Britain are still unknown. Neither has serious attention been devoted to the manner in which such technicians interacted with men of science on a day-to-day basis, or to the impact of their craft skills or trade practices on the development of science. My object in this brief account is to use the example of Richard Taylor, as represented by Brock and Meadows’ pioneering study, to review some of these important issues. (shrink)

Brock Macdonald1, Evi Vakiani2, Rhonda K Yantiss3, Jun Lee4, Robert S Brown Jr5, Samuel H Sigal61Division of Gastroenterology, Department of Medicine, University of California-San Francisco, San Francisco, CA, 2Department of Pathology, Memorial Sloan–Kettering Cancer Center, New York, NY, 3Department of Pathology and Laboratory Medicine, New York Weill Cornell Medical College, New York, NY, 4Division of Nephrology, Department of Medicine, Weill Cornell Medical College, New York, NY, 5Division of Gastroenterology, Department of Medicine, Columbia University College of Physicians and Surgeons, New (...) York, NY, 6Division of Gastroenterology and Hepatology, Department of Medicine, New York University, New York, NY, USA: The use of sirolimus as an alternative to calcineurin inhibitors for posttransplant immunosuppression is associated with a variety of inflammatory conditions. In this report, we describe the case of a 34-year-old man who developed abnormal liver tests 6 years after live-donor kidney transplantation and 5 years after initiation of sirolimus-based immunosuppression. Elevated aminotransferase levels persisted after withdrawal of potentially hepatotoxic medications, and serologic evaluation for viral hepatitis, autoimmune disease, and genetic disorders was unrevealing. Liver biopsy revealed prominent hepatocellular injury associated with a mixed inflammatory infiltrate and liver tests normalized within 2 weeks of discontinuation of sirolimus. In this report, we review previous reports of sirolimus hepatotoxicity and propose a unifying hypothesis for the various inflammatory conditions that have been attributed to sirolimus.Keywords: sirolimus, immunosuppression, transplant, inflammatory conditions, hepatotoxicity. (shrink)

Is there enough progress in philosophy? It is notable that even within the discipline, opinions are divided. Optimists think there is more than enough progress in philosophy. Pessimists think we could and should do better. In this chapter I defend an optimistic answer to this question.

If Saint Thomas Aquinas was a great theologian, it is in no small part because he was a great philosopher. And he was a great philosopher because he was a great metaphysician. In the twentieth century, metaphysics was not much in vogue, among either theologians or even philosophers; but now it is making a comeback, and once the contours of Thomas's metaphysical vision are glimpsed, it looks like anything but a museum piece. It only needs some dusting off. Many are (...) studying Thomas now for the answers that he might be able to give to current questions, but he is perhaps even more interesting for the questions that he can raise regarding current answers: about the physical world, about human life and knowledge, and (needless to say) about God. This book is aimed at helping those who are not experts in medieval thought to begin to enter into Thomas's philosophical point of view. Along the way, it brings out some aspects of his thought that are not often emphasized in the current literature, and it offers a reading of his teaching on the divine nature that goes rather against the drift of some prominent recent interpretations. (shrink)

Corruption is a pervasive problem across the world and is regularly ranked as among the greatest global challenges. Considering the role that corruption plays in exacerbating deprivation and fuelling social tension, peaceful and just societies are unlikely to come about without tackling corruption. Addressing corruption should be a high priority for those concerned with poverty eradication, peace, security, and justice. Yet, curiously, corruption has not yet been the focus of any books by philosophers working on global justice topics. Corruption and (...) Global Justice does so. Author Gillian Brock offers a normatively justified account of how to allocate responsibilities for addressing corruption across the many agents who can and should play a role. In order to know who should take responsibility and how they should do so, we need to understand multiple forms of corruption, the corruption risks associated with various activities, the interventions that tackle corruption effectively, and current policy and legal frameworks in place for addressing corruption. In addition, Brock proposes a new framework for navigating responsibility to address injustice, one that is action-oriented and forward-looking. Adopting an agent-empowering approach and harnessing the power of joining forces in effective collective action, Corruption and Global Justice addresses a significant global problem in a comprehensive way, providing the tools we need for progress as we collaborate to tackle this global scourge. (shrink)