It is proposed that the perturbation of the differentiated state in cancer is related to alterations in DNA methylation as well as to alterations in methylation of other cellular molecules, leading to an imbalance in global cellular methylation. It is hypothesized that the global imbalance in methylation is reflected in the enhanced levels of transmethylation seen in many cancer cell types as well as in a number of undermethylated molecules.

: Protection of human subjects from investigators' conflicts of interest is critical to the integrity of clinical investigation. Personal financial conflicts of interest are addressed by university policies, professional society guidelines, publication standards, and government regulation, but "intrinsic conflicts of interest"—conflicts of interest inherent in all clinical research—have received relatively less attention. Such conflicts arise in all clinical research endeavors as a result of the tension among professionals' responsibilities to their research and to their patients and both academic and financial (...) incentives. These conflicts should be disclosed to research subjects and managed as assiduously as are financial conflicts of interest. (shrink)

Robert M. Adams behauptet, daß Leibniz' zwei Konzeptionen der Körper als bloße Phänomene und als Aggregate von Substanzen konsistent und somit Bestandteile einer einzigen Theorie der Phänomene seien. Dagegen möchte ich hier zeigen, daß Adams' Strategie, Körper als intentionale Objekte der Perzeption zu verstehen - als objektive Realität von Ideen im kartesischen Sinn - nicht vereinbar damit ist, sie als Aggregate von Substanzen aufzufassen. Mit Adams stimme ich insofern überein, als Aggregate von Monaden sich nur im Geist als Einheit (...) finden, ich bestreite jedoch, daß nur im Geist die Aggregate dann auch sind. (shrink)

a comprehensive, somewhat Gricean theory of speech acts, including an account of communicative intentions and inferences, a taxonomy of speech acts, and coverage of many topics in pragmatics -/- .

Addressing the issue of how to read Nietzsche, this book presents an accessible series of essays for students and general readers on Nietzsche's individual works, written by such distinguished Nietzsche scholars as Frithjof Bergmann, Arthur Danto, Bernd Magnus, Christopher Middleton, Eric Blondel, Lars Gustaffson, Alexander Nehamas, Richard Schacht, Gary Shapiro, Hugh Silverman, and Ivan Soll. Among the works discussed are On the Genealogy of Morals, Beyond Good and Evil, Thus Spoke Zarathustra, Twilight of the Idols and The Will to Power.

Hereditary breast and ovarian cancers are frequently attributed to germline mutations in the tumor suppressor genes BRCA1 and BRCA2. BRCA1/2 act to repair double‐strand breaks (DSBs) and suppress the demise of unstable replication forks. Our work elucidated a dynamic interplay between BRCA2 and the WRN DNA helicase/exonuclease defective in the premature aging disorder Werner syndrome. WRN and BRCA2 participate in complementary pathways to stabilize replication forks in cancer cells, allowing them to proliferate. Whether the functional overlap of WRN and BRCA2 (...) is relevant to replication at gaps between newly synthesized DNA fragments, protection of telomeres, and/or metabolism of secondary DNA structures remain to be determined. Advances in understanding the mechanisms elicited during replication stress have prompted the community to reconsider avenues for cancer therapy. Insights from studies of PARP or topoisomerase inhibitors provide working models for the investigation of WRN's mechanism of action. We discuss these topics, focusing on the implications of the WRN‐BRCA2 genetic interaction under conditions of replication stress. (shrink)

Aversive experiences have been thought to provoke or exacerbate clinical depression. The present review provides a brief survey of the stress-depression literature and suggests that the effects of stressful experiences on affective state may be related to depletion of several neurotransmitters, including norepinephrine, dopamine, and serotonin. A major element in determining the neurochemical changes is the organism's ability to cope with the aversive stimuli through behavioral means. Aversive experiences give rise to behavioral attempts to cope with the stressor, coupled with (...) increased utilization and synthesis of brain amines to contend with environmental demands. When behavioral coping is possible, neurochemical systems are not overly taxed, and behavioral pathology will not ensue. However, when there can be no behavioral control over the stressful stimuli, or when the aversive experience is perceived as uncontrollable, increased emphasis is placed on coping through endogenous neurochemical mechanisms. Amine utilization increases appreciably and may exceed synthesis, resulting in a net reduction of amine stores, which in turn promotes or exacerbates affective disorder. The processes governing the depletions may be subject to sensitization or conditioning, such that exposure to traumatic experiences may have long-term repercussions when the organism subsequently encounters related stressful stimuli. With continued uncontrollable stimulation, adaptation occurs in the form of increased activity of synthetic enzymes, and levels of amines approach basal values. It is suggested that either the initial amine depletion provoked by aversive experiences or a dysfunction of the adaptive processes, resulting in persistent amine depletion, contributes to behavioral depression. Aside from the contribution of behavioral coping, several organismic, experiential, and environmental variables will influence the effects of aversive experiences on neurochemical activity, and may thus influence vulnerability to depression. (shrink)

In the clinical setting, questions of medical ethics raise a host of perplexing problems, often complicated by conflicting perspectives and the need to make immediate decisions. In this volume, bioethicists and physicians provide a nuanced, in-depth approach to the difficult issues involved in bioethics consultation. Addressing the needs of researchers, clinicians, and other health professionals on the front lines of bioethics practice, the contributors focus primarily on practical concerns -- whether ethics consultation is best done by individuals, teams, or committees (...) how an ethics consult service should be structured the need for institutional support and techniques and programs for educating and training staff -- without neglecting more theoretical considerations, such as the importance of character or the viability of organizational ethics. (shrink)

Recent stories of corporate insiders avoiding losses and, in some cases, generating enormous personal profits as their companies crumbled have led investors to question the integrity of American business and the fairness of the United States stock markets. The SEC tries to ensure the fairness of the stock markets by making and enforcing laws against unfair practices such as insider trading. In the United States, when insiders trade stock based on non-public information, they have broken the law and betrayed the (...) trust that has been placed in them.This study used student subjects to test the relationship between the likelihood of trading based on insider information and subjective probabilities of deterrents and motivations for insider trading. Expected gain, guilt, cynicism, and fairness of laws were the determinants that had a significant relationship with the intent to trade based on insider information. This study also found support for prospect theory with regard to insider trading. The results indicate that subjects are more likely to trade based on insider information to avoid a loss than to achieve an abnormal gain. The study also finds evidence of social desirability response bias. (shrink)

Book reviewed in this article: The New Health Care For Profit: Doctors and Hospitals in a Competitive Environment. Edited by Bradford H. Gray The Healing Mission and the Business Ethic. By Robert M. Cunningham The Medical Industrial Complex. By Stanley Wohl.

While we agree that the frame problem, as initially stated by McCarthy and Hayes (1969), is a problem that arises because of the use of representations, we do not accept the anti-representationalist position that the way around the problem is to eliminate representations. We believe that internal representations of the external world are a necessary, perhaps even a defining feature, of higher cognition. We explore the notion of dynamically created context-dependent representations that emerge from a continual interaction between working memory, (...) external input, and long-term memory. We claim that only this kind of representation, necessary for higher cognitive abilities such as counterfactualization, will allow the combinatorial explosion inherent in the frame problem to be avoided. (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)

Andrew Bailey's highly-regarded introductory anthology has been revised and updated in this new concise edition. First Philosophy : Knowing and Being brings together over thirty classic and contemporary readings in epistemology and metaphysics. Mindful of the intrinsic difficulty of the material, the editors provide comprehensive introductions both to each topic and to each individual selection. By presenting a detailed discussion of the historical and intellectual background to each piece, the editors enable readers to approach the material without unnecessary barriers to (...) understanding. A brief introduction to arguments is included, as are appendices on terminology and philosophical puzzles and paradoxes. (shrink)

This latest work by one of the leading thinkers in the area focuses, as the title suggests, on the question of exactly how context influences metaphor creation, interpretation, and use. Perhaps the...

In the Summa Theologiae ‘simplicity’ is treated as pre–eminent among the terms which may properly be used to describe the divine nature. The Question in which Thomas demonstrates that God must be ‘totally and in every way simple’ immediately follows the five proofs of God's existence, preceding the treatment of His other perfections, and being frequently used as the basis for proving them. Then in Question 13 ‘univocal predication' is held to be ‘impossible between God and creatures’ so that at (...) best ‘some things are said of God and creatures analogically’ because of the necessity of using ‘various and multiplied conceptions’ derived from our knowledge of created beings to refer to what in God is simple for ‘the perfections flowing from God to creatures… pre–exist in God unitedly and simply, whereas in creatures they are received divided and multiplied’ . In line with this, in the De Potentia Dei the treatment of analogical predication is integrated into that of ‘the Simplicity of the Divine Essence’ . Moreover, it lies at the root of Thomas's rejection of any possibility of a Trinitarian natural theology such as, for instance, St Anselm or Richard of St Victor had attempted to develop, on the grounds that ‘it is impossible to attain to the knowledge of the Trinity by natural reason’ since ‘we can know what belongs to the unity of the essence, but not what belongs to the distinction of the persons’ . Even modern minds sympathetic to Thomas have clearly found it difficult to understand his concern for the divine simplicity: in his Aquinas Lecture Plantinga speaks for many in stating that it is ‘a mysterious doctrine’ which is ‘exceedingly hard to grasp or construe’ and ‘it is difficult to see why anyone should be inclined to accept it’. Not surprisingly, therefore, some of the most widely read twentieth–century commentators on Aquinas have paid little attention to it. Increased interest has recently been shown in it, but a number of discussions pay insufficient attention to the historical context out of which Thomas's interest in the doctrine emerged, and consequently tend to misconstrue its nature. (shrink)

Assesses the ethical problems that doctors face every day and advocates a more universal code of medical ethics, one that draws on the traditions of religion and philosophy.

The puzzling case of the broken arm -- Hernias, diets, and drugs -- Why physicians cannot know what will benefit patients -- Sacrificing patient benefit to protect patient rights -- Societal interests and duties to others -- The new, limited, twenty-first-century role for physicians as patient assistants -- Abandoning modern medical concepts: doctor's "orders" and hospital "discharge" -- Medicine can't "indicate": so why do we talk that way? --"Treatments of choice" and "medical necessity": who is fooling whom? -- Abandoning informed (...) consent -- Why physicians get it wrong and the alternatives to consent: patient choice and deep value pairing -- The end of prescribing: why prescription writing is irrational -- The alternatives to prescribing -- Are fat people overweight? -- Beyond prettiness: death, disease, and being fat -- Universal but varied health insurance: only separate is equal -- Health insurance: the case for multiple lists -- Why hospice care should not be a part of ideal health care I: the history of the hospice -- Why hospice care should not be a part of ideal health care II: hospice in a postmodern era -- Randomized human experimentation: the modern dilemma -- Randomized human experimentation: a proposal for the new medicine -- Clinical practice guidelines and why they are wrong -- Outcomes research and how values sneak into finding of fact -- The consensus of medical experts and why it is wrong so often. (shrink)

After distinguishing two different meanings of the notion of a morality internal to medicine and considering a hypothetical case of a society that relied on its surgeons to eunuchize priest/cantors to permit them to play an important religious/cultural role, this paper examines three reasons why morality cannot be derived from reflection on the ends of the practice of medicine: (1) there exist many medical roles and these have different ends or purposes, (2) even within any given medical role, there exists (...) multiple, sometimes conflicting ends, and, most critically, (3) the ends of any practice such as medicine must come from outside the practice, that is, from the basic ends or purposes of human living. The paper concludes by considering whether these ends external to medicine are universally part of the moral reality or whether they are socially constructed. The paper argues that, even if various cultural accounts of the common, universal morality are socially constructed, they may, nevertheless, be reflections, however, imperfect, of a more universal common morality that should be thought of as real. Therefore, the morality of medicine must come from a more fundamental morality external to medicine. That external morality will be socially constructed, but may nevertheless reflect an underlying common morality. (shrink)

In its October 2001 issue, this journal published a series of articles questioning the Whole-Brain-based definition of death. Much of the concern focused on whether somatic integration - a commonly understood basis for the whole-brain death view - can survive the brain's death. The present article accepts that there are insurmountable problems with whole-brain death views, but challenges the assumption that loss of somatic integration is the proper basis for pronouncing death. It examines three major themes. First, it accepts the (...) claim of the "disaggregators" that some behaviors traditionally associated with death can be unbundled, but argues that other behaviors (including organ procurement) must continue to be associated. Second, it rejects the claims of the "somaticists," that the integration of the body is critical, arguing instead for equating death with the irreversible loss of "embodied consciousness," that is, the loss of integration of bodily and mental function. Third, it defends higher-brain views against the charge that they are necessarily "mentalist," that is, that they equate death with losing some mental function such as consciousness or personhood. It argues, instead, for the integration of bodily and mental function as the critical feature of human life and that its irreversible loss constitutes death. (shrink)

While twentieth-century medical ethics has focused on the duty of physicians to benefit their patients, the next century will see that duty challenged in three ways. First, we will increasingly recognize that it is unrealistic to expect physicians to be able to determine what will benefit their patients. Either they limit their attention to medical well-being when total well-being is the proper end of the patient or they strive for total well-being, which takes them beyond their expertise. Even within the (...) medical sphere, they have no basis for choosing among the proper medical goals for medicine. Also, there are many plausible strategies for relating predicted benefits to harms, and physicians cannot be expert in picking among these strategies. Second, increasingly plausible ethical systems recognize that in some cases, patient benefit must be sacrificed to protect patient rights including the right to the truth, to have promises kept, to have autonomy respected, and to not be killed. Third, ethics of the next century will increasingly recognize that some patient benefits must be sacrificed to fulfill duties to others - either the duty to serve the interests of others or other duties such as keeping promises, telling the truth, and, particularly, promoting justice. Physicians in the twenty-first century will be seen as having a new, more limited duty to assist the patient in pursuing the patient's understanding of the patient's interest within the constraints of deontological ethical principles and externally imposed duties to promote justice. The result will be a duty to be loyal to the consumer of health care with the recognition that often this will mean that the physician is not permitted to pursue the physician's understanding of the patient's well-being. (shrink)

Modern historical criticism of the gospels and Christian origins began in the seventeenth century largely as an attempt to debunk the Christian religion as a pious fraud. The gospels were seen as bits of priestcraft and humbug of a piece with the apocryphal Donation of Constantine. In the few centuries since Reimarus and his critical kin, historical criticism has been embraced and assimilated by many Christian scholars who have seen in it the logical extension of the grammatico-historical method of the (...) Reformers. The new views of New Testament exegesis and of early Christian history are important and well known. Many New Testament scholars would now hold with Schweitzer and Bultmann that Jesus was a preacher of the imminent end of the world. He may have secretly considered himself to be the Messiah, or he may have simply sought to pave the way for another, the apocalyptic Son of Man. After his execution, his disciples' experiences of his resurrection forced on them a conclusion already implicit in his teachings and personal piety: that Jesus was indeed, or had become, the Messiah, and was in fact God's Son. They expected he would soon return as the Son of Man he had predicted. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Kennedy Institute of Ethics Journal 13.3 (2003) 189-192 [Access article in PDF] Is There a Common Morality? Robert M. VeatchSenior EditorOne of the most exciting and important developments in recent ethical theory—especially bioethical theory—is the emergence of the concept of "common morality." Some of the most influential theories in bioethics have endorsed the notion using it as the starting point of their systems. This issue of the Journal (...) is devoted to these developments.The core idea of a common morality is that all humans—at least all morally serious humans—have a pretheoretical awareness of certain moral norms. The claim is that normal humans intuit or in some other way know that there is something wrong with things like lying or breaking promises or killing people. These purportedly universally shared insights can provide the raw data from which ethical theories are constructed. As such, they are perhaps analogous to the raw sense data that are relied on in the natural sciences to launch the construction of scientific theories and accounts of the nature of reality. Some common morality theorists suggest an analogy between the natural and the moral sciences.In the natural sciences there is a widely shared belief that some raw sensory data are perceived by all normal humans and provide the basis for the construction of various scientific theories. For example, it is widely believed that all normal humans looking at the top light on a traffic signal perceive something that in English is called "red." Of course, different cultures will use different language to describe this experience. They may parse the boundaries differently (varying on the exact borderline between red and orange), provide widely differing accounts of why the experience of "red" occurs, and eventually generate significantly different theoretical formulations to explain the experience of redness. Moreover, some individuals may look at that top light of the traffic signal and not see color at all. One generally, however, does not account for this by denying there is any objective, generally shared basis for the experience that produces a sensation of redness in normal people. One simply explains the experience of the one who fails to see color by positing a defect in perception, called "color-blindness."Some moral theorists suggest that something analogous happens when humans look at the moral scene. The claim is that all normal humans in all places and cultures "see" certain moral requiredness. They see that some behaviors are, in some sense, generally wrong; that other behaviors are generally right; that [End Page 189] some character traits are generally praiseworthy, others blameworthy. No sophisticated common morality theorist denies that, as with color-blindness, there may be occasional outliers who for one reason or another fail to intuit or perceive these simple, abstract moral norms. Certainly, people in different cultures will define the terms differently, will recognize different limits on the norms, and will construct different theories to account for their experience. The primitive idea that there is something generally wrong with killing other humans will be articulated very differently in different cultures—some referring to the "sacredness of life;" others to a duty not to kill, a right to life, or a prohibition on killing the innocent. Some may extend the insight to a duty to prolong living, others limit it merely to a prohibition of direct, active killing. Some may endorse more exceptions—for killing of unjust aggressors, for killing in just war, for killing in self-defense; others, such as pacifists, will be much more stingy in doling out exceptions. Certainly, people at different times and places will articulate the norms in different language and embed them in different theories. The basic claim of common morality theorists, however, is that there is some primitive, pretheoretical insight that is shared by all normal, morally serious persons.Recently, the notion of a common morality has served as a starting point for bioethical theories as diverse as Bernard Gert, Charles Culver, and Danner Clouser's Bioethics: A Return to Fundamentals (1997) and the latest edition of Tom Beauchamp and James Childress's Principles of Biomedical Ethics... (shrink)

: Research by Siminoff and colleagues reveals that many lay people in Ohio classify legally living persons in irreversible coma or persistent vegetative state (PVS) as dead and that additional respondents, although classifying such patients as living, would be willing to procure organs from them. This paper analyzes possible implications of these findings for public policy. A majority would procure organs from those in irreversible coma or in PVS. Two strategies for legitimizing such procurement are suggested. One strategy would be (...) to make exceptions to the dead donor rule permitting procurement from those in PVS or at least those who are in irreversible coma while continuing to classify them as living. Another strategy would be to further amend the definition of death to classify one or both groups as deceased, thus permitting procurement without violation of the dead donor rule. Permitting exceptions to the dead donor rule would require substantial changes in law—such as authorizing procuring surgeons to end the lives of patients by means of organ procurement—and would weaken societal prohibitions on killing. The paper suggests that it would be easier and less controversial to further amend the definition of death to classify those in irreversible coma and PVS as dead. Incorporation of a conscience clause to permit those whose religious or philosophical convictions support whole-brain or cardiac-based death pronouncement would avoid violating their beliefs while causing no more than minimal social problems. The paper questions whether those who would support an exception to the dead donor rule in these cases and those would support a further amendment to the definition of death could reach agreement to adopt a public policy permitting organ procurement of those in irreversible coma or PVS when proper consent is obtained. (shrink)

It is not too great an exaggeration to claim that On the Origin of Species was, along with Das Kapital, one of the two most significant works in the intellectual history of the nineteenth century. As George Henry Lewes wrote in 1868, ‘No work of our time has been so general in its influence’. However, the very generality of the influence of Darwin’s work provides the chief problem for the intellectual historian. Most books and articles on the subject assert the (...) influence but remain very imprecise about its nature. It is very difficult indeed to assess what it was about the Darwinian theory which was so influential and how its influence was felt. This problem in Victorian intellectual history intersects with a related one in the history of science. There has been a tendency on the part of historians of science to isolate Darwin in two related ways. The first is to single him out from the mainstream of nineteenth-century naturalism in Britain and allow ‘Darwinism’ to stand duty for the wider movement of which it was in fact but a part. The second is the tendency to single out his evolutionary theory and to demarcate it sharply from those of his predecessors and contemporaries. According to this interpretation Darwin stood alone as a real, empirical scientist and provided the first genuinely scientific hypothesis for the process by which evolution might have occurred. The theories of the other main evolutionists—Erasmus Darwin, Lamarck, Chambers, Spencer, and Wallace—were more or less besmirched by ideological, anthropomorphic, or other ‘non-scientific’ factors or by the uses to which they were put by their authors. Charles Darwin is thus made to stand out as a figure of comparatively unalloyed scientific status and is treated in relative isolation from the social and intellectual context in which he worked and into which his theory was received. (shrink)

The concept of care and a related ethical theory of care have emerged as increasingly important in biomedical ethics. This essay outlines a series of questions about the conceptualization of care and its place in ethical theory. First, it considers the possibility that care should be conceptualized as an alternative principle of right action; then as a virtue, a cluster of virtues, or as a synonym for virtue theory. The implications for various interpretations of the debate of the relation of (...) care and justice are then explored, suggesting three possible meanings for that contrast. Next, the possibility that care theorists are taking up the debate over the relation between principles and cases is considered. Finally, it is suggested that care theorists may be pressing for consideration of an entirely new question in moral theory: the assessment of the normative appropriateness of relationships. Issues needing to be addressed in an ethic of relationships are suggested. (shrink)

It is commonly believed in research ethics that some form of equipoise is a necessary condition for justifying randomized clinical trials, that without it clinicians are violating the moral duty to do what is best for the patient. Recent criticisms have shown how complex the concept of equipoise is, but often retain the commitment to some form of equipoise for randomization to be justified. This article rejects that claim. It first asks for what one should be equally poised (scientific or (...) clinical equipoise), then asks who should be equally poised (scientist, clinician, or subject), and finally asks why any of these players need be equally poised between treatment options. The article argues that only the subject's evaluation of the options is morally relevant and that even the subject need not be equally poised or indifferent between the options in order to volunteer for randomization. All that is needed is adequately informed, free, and unexploited consent. It concludes equipoise is irrelevant. (shrink)

: Free-market libertarians have long supported incentives to increase organ procurement, but those oriented to justice traditionally have opposed them. This paper presents the reasons why those worried about justice should reconsider financial incentives and tolerate them as a lesser moral evil. After considering concerns about discrimination and coercion and setting them aside, it is suggested that the real moral concern should be manipulation of the neediest. The one offering the incentive (the government) has the resources to eliminate the basic (...) needs that pressure the poor into a willingness to sell. It is unethically manipulative to withhold those resources and then offer payment for organs. Nevertheless, the poor have been left without basic necessities for 20 years since the passage of the prohibition on incentives. As long as the government continues to withhold a decent minimum of welfare, liberals should, with shame, cease opposing financial incentives for organ procurement. (shrink)

A model for ethical problem solving -- Values in health and illness -- What is the source of moral judgments? -- Benefiting the patient and others : duty to do good and avoid harm -- Justice : allocation of health resources -- Autonomy -- Veracity : honesty with patients -- Fidelity : promise-keeping, loyalty to patients, and impaired professionals -- Avoidance of killing -- Abortion, sterilization, and contraception -- Genetics, birth, and the biological revolution -- Mental health and behavior control (...) -- Confidentiality : ethical disclosure of medical information -- Organ transplants -- Health insurance, health system planning, and rationing -- Experimentation on human subjects -- Consent and the right to refuse treatment -- Death and dying. (shrink)