In the atavistic model of cancer progression, tumor cell dedifferentiation is interpreted as a reversion to phylogenetically earlier capabilities. The more recently evolved capabilities are compromised first during cancer progression. This suggests a therapeutic strategy for targeting cancer: design challenges to cancer that can only be met by the recently evolved capabilities no longer functional in cancer cells. We describe several examples of this target‐the‐weakness strategy. Our most detailed example involves the immune system. The absence of adaptive immunity in immunosuppressed (...) tumor environments is an irreversible weakness of cancer that can be exploited by creating a challenge that only the presence of adaptive immunity can meet. This leaves tumor cells more vulnerable than healthy tissue to pathogenic attack. Such a target‐the‐weakness therapeutic strategy has broad applications, and contrasts with current therapies that target the main strength of cancer: cell proliferation. (shrink)

This essay is composed of five stories written by practicing physicians about their patients. Each clinical story describes a challenging ethical condition–potential abuse of medical power, gravely ill and probably over-treated newborns, iatrogenic narcotic addiction, deceived dying people. Rather than singling out one ethical conflict to resolve or adjudicate, the authors attempt, through literary methods, to grasp the singular experiences of their patients and to act according to the deep structures of their patients' lives. Examining these five stories with simple (...) literary tools–attention to narrative frames, time, plot, and desire–reveals the mechanisms through which acts of writing and reading contribute to clinical clarity and ethical actions. (shrink)

At the 1983 Summer Conference on the Institute on Religion in an Age of Science, working groups chaired by the coauthors outlined some of the prospects for the use of somatic and germ line genetic engineering and related biological technologies to alleviate disease and to modify human behavior. They then offered a series of recommendations concerning the application of genetic engineering to persons and the monitoring of medical research and therapy.

This paper is one of the four interrelated action agenda papers resulting from the National Summit on Public Health Legal Preparedness convened in June 2007 by the Centers for Disease Control and Prevention and multi-disciplinary partners. Each of the action agenda papers deals with one of the four core elements of public health legal preparedness: laws and legal authorities; competency in using those laws; coordination of law-based public health actions; and information. Options presented in this paper are for consideration by (...) policy makers and practitioners — in all jurisdictions and all relevant sectors and disciplines — with responsibilities for all-hazards emergency preparedness.Advancing and protecting the public's health depends upon the coordination of actions by many, diverse partners. For effective public health preparedness, there must be effective coordination of legal tools and law-based strategies across local, state, tribal, and federal jurisdictions, and also across sectors such as public health, health care, emergency management, education, law enforcement, community design, and academia. (shrink)

A novel Protocol Ethics Tool Kit (‘Ethics Tool Kit’) has been developed by a multi-stakeholder group of the Multi-Regional Clinical Trials Center of Brigham and Women9s Hospital and Harvard. The purpose of the Ethics Tool Kit is to facilitate effective recognition, consideration and deliberation of critical ethical issues in clinical trial protocols. The Ethics Tool Kit may be used by investigators and sponsors to develop a dedicated Ethics Section within a protocol to improve the consistency and transparency between clinical trial (...) protocols and research ethics committee reviews. It may also streamline ethics review and may facilitate and expedite the review process by anticipating the concerns of ethics committee reviewers. Specific attention was given to issues arising in multinational settings. With the use of this Tool Kit, researchers have the opportunity to address critical research ethics issues proactively, potentially speeding the time and easing the process to final protocol approval. (shrink)

This paper is one of the four interrelated action agenda papers resulting from the National Summit on Public Health Legal Preparedness convened in June 2007 by the Centers for Disease Control and Prevention and multi-disciplinary partners. Each of the action agenda papers deals with one of the four core elements of public health legal preparedness: laws and legal authorities; competency in using those laws; coordination of law-based public health actions; and information. Options presented in this paper are for consideration by (...) policy makers and practitioners — in all jurisdictions and all relevant sectors and disciplines — with responsibilities for all-hazards emergency preparedness.Advancing and protecting the public's health depends upon the coordination of actions by many, diverse partners. For effective public health preparedness, there must be effective coordination of legal tools and law-based strategies across local, state, tribal, and federal jurisdictions, and also across sectors such as public health, health care, emergency management, education, law enforcement, community design, and academia. (shrink)

Late in 1990, the Center for the Study of Ethics in the Professions at Illinois Institute of Technology (lIT) received a grant of more than $200,000 from the National Science Foundation to try a campus-wide approach to integrating professional ethics into its technical curriculum.! Enough has now been accomplished to draw some tentative conclusions. I am the grant's principal investigator. In this paper, I shall describe what we at lIT did, what we learned, and what others, especially philosophers, can learn (...) from us. We set out to develop an approach that others could profitably adopt. I believe that we succeeded. (shrink)

Background: The Declaration of Helsinki, the World Medical Association’s statement of ethical guidelines regarding medical research, is published in the three official languages of the WMA: English, French and Spanish.Methods: A detailed comparison of the three official language versions was carried out to determine ways in which they differed and ways in which the wording of the three versions might illuminate the interpretation of the document.Results: There were many minor linguistic differences between the three versions. However, in paragraphs 1, 6, (...) 29, 30 and in the note of clarification to paragraph 29, there were differences that could be considered potentially significant in their ethical relevance.Interpretation: Given the global status of the Declaration of Helsinki and the fact that it is translated from its official versions into many other languages for application to the ethical conduct of research, the differences identified are of concern. It would be best if such differences could be eliminated but, at the very least, a commentary to explain any differences that are unavoidable on the basis of language or culture should accompany the Declaration of Helsinki. This evidence further strengthens the case for international surveillance of medical research ethics as has been proposed by the WMA. (shrink)

BackgroundDespite rapid growth of the scientific literature, no consensus guidelines have emerged to define the optimal criteria for editors to grade submitted manuscripts. The purpose of this project was to assess the peer reviewer metrics currently used in the surgical literature to evaluate original manuscript submissions.MethodsManuscript grading forms for 14 of the highest circulation general surgery-related journals were evaluated for content, including the type and number of quantitative and qualitative questions asked of peer reviewers. Reviewer grading forms for the seven (...) surgical journals with the higher impact factors were compared to the seven surgical journals with lower impact factors using Fisher’s exact tests.ResultsImpact factors of the studied journals ranged from 1.73 to 8.57, with a median impact factor of 4.26 in the higher group and 2.81 in the lower group. The content of the grading forms was found to vary considerably. Relatively few journals asked reviewers to grade specific components of a manuscript. Higher impact factor journal manuscript grading forms more frequently addressed statistical analysis, ethical considerations, and conflict of interest. In contrast, lower impact factor journals more commonly requested reviewers to make qualitative assessments of novelty/originality, scientific validity, and scientific importance.ConclusionSubstantial variation exists in the grading criteria used to evaluate original manuscripts submitted to the surgical literature for peer review, with differential emphasis placed on certain criteria correlated to journal impact factors. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Hume Studies Volume XXIII, Number 2, November 1997, pp. 227-244 Hume on Geometry and Infinite Divisibility in the Treatise H. MARK PRESSMAN Scholars have recognized that in the Treatise "Hume seeks to find a foundation for geometry in sense-experience."1 In this essay, I examine to what extent Hume succeeds in his attempt to ground geometry visually. I argue that the geometry Hume describes in the Treatise faces a serious (...) set of problems. Geometric Lines Hume maintains that ideas "are images" (T 6) which may be called up "when I shut my eyes" (T 3). "That we may fix the meaning of a word, figure," according to Hume, "we may revolve in our mind the ideas of circles, squares, parallelograms, triangles of different sizes and proportions, and may not rest on one image or idea" (T 22). As Arthur Pap notes, "'Idea' is in Hume's usage synonymous with 'mental image'." D.C.G. MacNabb also notes that "Hume thought of ideas as images, and primarily as visual images."2 When Hume argues, then, that "we have the idea of indivisible points, lines and surfaces conformable to the [geometer's] definition" (T 44), he is arguing that we have mental images of geometry's points, lines and planes. Consider geometric lines first. Geometers define a line "to be length without breadth or depth" (T 42). It is not apparent to everyone that we have mental images of such lines. According to "L'Art de penser" (T 43), published in 1662, it is impossible "to conceive a length without any breadth" (T 43). H. Mark Pressman is at the Department of Philosophy, University of California, Davis, 1238 Social Sciences and Humanities Building, Davis CA 95616-8673 USA. email: [email protected] 228 H. Mark Pressman We can only by an abstraction "consider the one without regarding the other" (T 43). Hume, however, offers "clear proof" (T 44), in the form of two arguments, that we actually possess ideas or mental images of geometry's lines. First, we have ideas or mental images of lengths with breadth, though these are supposed never to be without breadth and thus not geometric lines. (A mental image oflength is also a mental image with length, just as "to say the idea of extension agrees to any thing, is to say it is extended" [T 240].) Hume reduces to absurdity the view that our mental images of length are always with breadth and thus not images of geometric lines. If our length-images were always with breadth, then our mental images would be endlessly divisible in breadth, since they would always have some positive breadth (T 43). But no mental image is endlessly divisible, for the mind arrives "at an end in the division of its ideas, nor are there any possible means of evading the evidence of this conclusion" (T 27). We thus have an idea or image of length without (divisible) breadth conforming to the geometer's definition (T 44). Second, we can imagine or picture the termination of a geometric plane. But a geometric plane must terminate in a geometric line (T 44). (Proof: Assume L is a line with breadth which terminates plane P. Since L has breadth, L must contain at least two parts, w and y, exactly one of which actually terminates P. But whether it is w or y, L doesn't terminate P, which was the assumption.) Since we can picture the termination of a geometric plane, we can picture a geometric line, length without divisible breadth. It is one thing to have ideas or mental images of geometric lines which may be called up "when I shut my eyes" (T 3). It is another for such objects actually to exist "in nature." The conceptualist holds that though (a) geometry 's points, lines and planes are ideas, nevertheless (b) there are no such things in nature and that (c) there can't be such things in nature: [T]he objects of geometry... are mere ideas in the mind, and not only never did, but never can exist in nature. They never did exist; for no one will pretend to draw a line or make a... (shrink)

This volume presents significant developments in the field of Montague Grammar and outlines its past and future contributions to philosophy and linguistics. The contents are as follows: Introduction by Steven Davis and Marianne Mithun Emmon Bach, "Montague Grammar and Classical Transformational Grammar" Barbara H. Partee, "Constraining Transformational Montague Grammar: A Framework and a Fragment" James D. McCawley, "Helpful Hints to the Ordinary Working Montague Grammarian" Terence Parsons, "Type Theory and Ordinary Language" David R. Dowty, "Dative 'Movement' and Thomason's Extensions of (...) Montague Grammar" Muffy E. A. Siegel, "Measure Adjectives in Montague Grammar" Michael Bennett, "Mass Nouns and Mass Terms in Montague Grammar" Jeroen Groenendijk and Martin Stokhof, "Infinitives and Context in Montague Grammar" James Waldo, "A PTQ Semantics for Sortal Incorrectness". (shrink)

Adequate treatment of pain is essential to alleviate suffering, yet studies show that patients with terminal or serious illness receive inadequate pain relief. In the case of terminally ill patients, adequate palliation of pain may be likely to reduce requests for physician-assisted suicide. This issue of the journal addresses barriers to effective pain relief and suggests how treatment of pain can be improved. The symposium features the Pain Relief Act, which is designed to provide practitioners who prescribe controlled substances for (...) pain with protection from inappropriate legal sanctions. The Act is the product of the Project on Legal Constraints on Access to Effective Pain Relief, whose principal investigators were Nancy Neveloff Dubler, LL.B., Sandra H. Johnson, J.D., LL.M., Robert J. Levine, M.D., and Benjamin W. Moulton, J.D., M.P.H.The Project was supported by the Mayday Fund and the Emily Davie and Joseph S. Kornfeld Foundation. (shrink)

Adequate treatment of pain is essential to alleviate suffering, yet studies show that patients with terminal or serious illness receive inadequate pain relief. In the case of terminally ill patients, adequate palliation of pain may be likely to reduce requests for physician-assisted suicide. This issue of the journal addresses barriers to effective pain relief and suggests how treatment of pain can be improved. The symposium features the Pain Relief Act, which is designed to provide practitioners who prescribe controlled substances for (...) pain with protection from inappropriate legal sanctions. The Act is the product of the Project on Legal Constraints on Access to Effective Pain Relief, whose principal investigators were Nancy Neveloff Dubler, LL.B., Sandra H. Johnson, J.D., LL.M., Robert J. Levine, M.D., and Benjamin W. Moulton, J.D., M.P.H.The Project was supported by the Mayday Fund and the Emily Davie and Joseph S. Kornfeld Foundation. (shrink)

This selection of D. H. Mellor's work demonstrates the wide ranging originality of his work. It gathers together sixteen major papers on related topics. Together they form a complete modern metaphysics. The first five papers are on aspects of the mind: on our 'selves', their supposed subjectivity and how we refer to them, on the nature of conscious belief and on computational and physicalist theories of the mind. The next five papers deal with dispositions, natural kinds, laws of nature and (...) how they involve natural necessity, universals and objective chances, and the relation between properties and predicates. Then follow three papers about the relations between time, change and causation, the nature of individual causes and effects and of the causal relation between them, and how causation depends on chance. The last three papers discuss the relation between chance and degrees of belief, give a solution to the problem of induction, and argue for an objective interpretation of decision theory. (shrink)

[D. H. Mellor] Kant's claim that our knowledge of time is transcendental in his sense, while false of time itself, is true of tenses, i.e. of the locations of events and other temporal entities in McTaggart's A series. This fact can easily, and I think only, be explained by taking time itself to be real but tenseless. /// [J. R. Lucas] Mellor's argument from Kant fails. The difficulties in his first Antinomy are due to topological confusions, not the tensed nature (...) of time. Nor are McTaggart' s difficulties due to the tensed nature of time. The ego-centricity of tensed discourse is an essential feature of communication between selves, each of whom refers himself as 'I', and is required for talking about time as well as experience and agency. Arguments based on the Special Theory are misconceived. Some rest on a confused notion of 'topological simultaneity'. In the General Theory a cosmic time is defined, as also in quantum mechanics, where a natural present is defined by a unique hyperplane of collapse into eigen-ness. (shrink)

This article is the text of an interview with D. H. Mellor conducted by Andrew Pyle and first published in the Spring 1993 issue of the philosophical journal Cogito.