Neurodegenerative diseases are becoming increasingly common as life expectancy increases. Recent years have seen tremendous progress in the identification of genes that cause these diseases. While mutations have been found and cellular processes defined that are altered in the disease state, the identification of treatments and cures has proven more elusive. The process of finding drugs and therapies to treat human diseases can be slow, expensive and frustrating. Can model organisms such as Drosophila speed the process of finding cures and (...) treatments for human neurodegenerative diseases? We pose three questions, (1) can one mimic the essential features of human diseases in an organism like Drosophila, (2) can one cure a model organisms of human disease and (3) will these efforts accelerate the identification of useful therapies for testing in mice and ultimately humans? Here we focus on the use of Drosophila to identify potential treatments for neurodegenerative diseases such as Huntington's and we discuss how well these therapies translate into mammalian systems. BioEssays 26:485–496, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Activating the ERK pathway (extracellular signal‐regulated kinase pathway) has proven beneficial in several models of Huntington's disease (HD), and drugs that are protective in HD models have recently been found to activate ERK. Thus, the ERK cascade may be a potential target for therapeutic intervention in this currently untreatable disorder. HD is caused by an expanded polyglutamine repeat in the huntingtin (Htt) protein that actuates a diverse set of pathogenic mechanisms. In response to mutant Htt, ERK is activated and directs (...) a protective transcriptional response and inhibits caspase activation. Paradoxically, Htt also interferes with several signaling events of the ERK pathway. Mutant Htt compromises the ERK‐dependent transcriptional response to corticostriatal BDNF signaling. Mutant Htt also hinders glutamate uptake from the synaptic cleft by down‐regulating ERK‐dependent expression of glutamate transporters, leaving cells vulnerable to excitotoxicity. Some of this cellular complexity can be capitalized on to achieve selective activation of ERK, which can be protective. (shrink)

Disputes regarding the ethics of work by children have intensified in recent years, with little resolution. The impasses stem from failure to recognize the diverse forms of child work and a lack of empirical research regarding its causes and consequences. We report on data gathered in Brazil’s export-oriented shoe industry, which is notorious for the employment of children. Central findings are: 1) the causes of child work have less to do with backwardness and more to do with how shoe workers (...) are integrated into the global order; 2) local employers and children regard this work as benign, but the U.S. government sees it as hazardous to children and unfair to U.S. producers; 3) efforts to remove children from the shoe industry have been frustrated by local resistance and raise ethical questions; and 4) in certain circumstances, efforts to eliminate hazards from the workplace are morally superior to campaigns to remove childworkers from employment. (shrink)

The large numbers of children working in developing countries continue to provoke calls for an end to such employment. However, many reformers argue that efforts should focus on ending the exploitation of children rather than depriving them of all opportunities to work. This posture reflects recognition of the multiplicity of needs children have and the diversity of situations in which they work. Unfortunately, research typically neglects these complexities and fails to distinguish between types of labor market jobs, dismisses household chores (...) as irrelevant, and conceptualizes children’s needs largely in terms of the education they require for successful careers. Based on data collected in schools in Franca, Brazil, where children often combine school with work in the shoe industry, this study first examined the implications of labor market jobs and household work for their health, life satisfaction, and education. Analyses suggested that both forms of work negatively affected children’s welfare, but the effects of household work were more extensive, especially for girls. The second part focused on children with labor market jobs and examined how facets of their jobs as well as their after-work household duties affected their welfare. A lack of discretion on the job undermined the health of both boys and girls, higher pay adversely affected boys’ education, and housework had detrimental effects on all indicators of girls’ welfare. This paper discusses the implications of these findings for further research and suggests the needs for attention to different forms of work activities within families. It concludes with suggestions for multinationals sourcing in developing areas that go beyond the usual calls for ridding their facilities and supply networks of child workers. (shrink)

Disputes regarding the ethics of work by children have intensified in recent years, with little resolution. The impasses stem from failure to recognize the diverse forms of child work and a lack of empirical research regarding its causes and consequences. We report on data gathered in Brazil’s export-oriented shoe industry, which is notorious for the employment of children. Central findings are: 1) the causes of child work have less to do with backwardness and more to do with how shoe workers (...) are integrated into the global order; 2) local employers and children regard this work as benign, but the U.S. government sees it as hazardous to children and unfair to U.S. producers; 3) efforts to remove children from the shoe industry have been frustrated by local resistance and raise ethical questions; and 4) in certain circumstances, efforts to eliminate hazards from the workplace are morally superior to campaigns to remove childworkers from employment. (shrink)

The large numbers of children working in developing countries continue to provoke calls for an end to such employment. However, many reformers argue that efforts should focus on ending the exploitation of children rather than depriving them of all opportunities to work. This posture reflects recognition of the multiplicity of needs children have and the diversity of situations in which they work. Unfortunately, research typically neglects these complexities and fails to distinguish between types of labor market jobs, dismisses household chores (...) as irrelevant, and conceptualizes children’s needs largely in terms of the education they require for successful careers. Based on data collected in schools in Franca, Brazil, where children often combine school with work in the shoe industry, this study first examined the implications of labor market jobs and household work for their health, life satisfaction, and education. Analyses suggested that both forms of work negatively affected children’s welfare, but the effects of household work were more extensive, especially for girls. The second part focused on children with labor market jobs and examined how facets of their jobs as well as their after-work household duties affected their welfare. A lack of discretion on the job undermined the health of both boys and girls, higher pay adversely affected boys’ education, and housework had detrimental effects on all indicators of girls’ welfare. This paper discusses the implications of these findings for further research and suggests the needs for attention to different forms of work activities within families. It concludes with suggestions for multinationals sourcing in developing areas that go beyond the usual calls for ridding their facilities and supply networks of child workers. (shrink)

Dissociative experiences have been associated with diachronic disunity. Yet, this work is in its infancy. Dissociative identity disorder is characterized by different identity states reporting their own relatively continuous sense of self. The degree to which patients in dissociative identity states experience diachronic unity has not been empirically explored. This study examined the degree to which patients in dissociative identity states experienced diachronic unity. Participants were DID adults assessed in adult and child identity states, adults with a psychotic illness, adults (...) from the general population, children from the general population and adults imagining themselves as children. They completed the Diachronic Disunity Scale, the Dissociative Experiences Scale, and the Self-Concept Clarity Scale. Diachronic disunity was not limited to psychiatric groups, but evident to some degree in all adult and child samples. The DID adult sample experienced more dissociation and self-confusion than the psychosis and adult comparison groups, but did not differ on the diachronic measure. DID patients in their child identity states and child comparisons showed disunity and were significantly different from child simulators, who showed relatively more unity. Results suggest that DID patients in either adult or child dissociative identity states, like those in other samples, do not universally experience themselves as having a consistent sense of self over time. (shrink)

In this book, Lawrence Hatab provides an accessible and provocative exploration of one of the best-known and still most puzzling aspects of Nietzsche's thought: eternal recurrence, the claim that life endlessly repeats itself identically in every detail. Hatab argues that eternal recurrence can and should be read literally, in just the way Nietzsche described it in the texts. The book offers a readable treatment of most of the core topics in Nietzsche's philosophy, all discussed in the light of the (...) consummating effect of eternal recurrence. Although Nietzsche called eternal recurrence his most fundamental idea, most interpreters have found it problematic or needful of redescription in other terms. For this reason, Hatab's book is an important and challenging contribution to Nietzsche scholarship. (shrink)

Howard Brody expresses concern that citing the “two cases that put futility on the map,” namely Helga Wanglie and Baby K, may be providing ammunition to the opponents of the concept of medical futility. He in fact joins well-known opponents of the concept of medical futility in arguing that it is one thing for the physician to say whether a particular intervention will promote an identified goal, quite another to say whether a goal is worth pursuing. In the latter instance, (...) physicians are laying themselves open “to the criticism of taking on basic value judgments that are more appropriately left to patients and their surrogates.” Brody states that in both the Wanglie and Baby K cases, the “basic value judgments” had to do with the worthiness of maintaining unconscious life via medical technology. He classifies this as “a question of professional integrity—but not a question of futility,” adding that “more than semantics hinges on this distinction.” The “more than semantics” factor is a pragmatic, even political one. Failure to make this distinction renders physicians “that much more suspect and less trustworthy in the public debate.”. (shrink)

How is it that sounds from the mouth or marks on a page—which by themselves are nothing like things or events in the world—can be world-disclosive in an automatic manner? In this fascinating and important book, Lawrence J. Hatab presents a new vocabulary for Heidegger’s early phenomenology of being-in-the-world and applies it to the question of language. He takes language to be a mode of dwelling, in which there is an immediate, direct disclosure of meanings, and sketches an extensive (...) picture of proto-phenomenology, how it revises the posture of philosophy, and how this posture applies to the nature of language. Representational theories are not rejected but subordinated to a presentational account of immediate disclosure in concrete embodied life. The book critically addresses standard theories of language, such that typical questions in the philosophy of language are revised in a manner that avoids binary separations of language and world, speech and cognition, theory and practise, realism and idealism, internalism and externalism. (shrink)

Key Concepts for Understanding Curriculum is an invaluable guide for all involved in curriculum matters. Originally published in 1992, and then re-released as two volumes, the third edition returns to a single volume and includes 21 key topics in the field. The topics comprise the latest trends and issues written in Marsh's clear and accessible style, and are an important source of material for an international readership at every level. The book is divided into six sections including: curriculum planning (...) and development; curriculum management; teaching perspectives; collaborative involvement in curriculum; and curriculum ideology. In this third edition many of the latest curriculum trends and issues are included such as standards-based frameworks, using technology in teaching and learning modes, standards based reforms, and politics of decision-making. (shrink)

Should the nation provide expensive care and scarce organs to convicted felons? We distinguish between two fields of justice: Medical Justice and Societal Justice. Although there is general acceptance within the medical profession that physicians may distribute limited treatments based solely on potential medical benefits without regard to nonmedical factors, that does not mean that society cannot impose limits based on societal factors. If a society considers the convicted felon to be a full member, then that person would be entitled (...) to at least a decent minimum level of care — which might include access to scarce life-saving organs. However, if criminals forfeit their entitlement to the same level of medical care afforded to all members of society, they still would be entitled to a kind of rudimentary decent minimum granted to all persons on simple humanitarian grounds. Almost certainly this entitlement would not include access to organ transplants. (shrink)

Erich Fromm was a political activist, psychologist, psychoanalyst, philosopher, and one of the most important intellectuals of the twentieth century. Known for his theories of personality and political insight, Fromm dissected the sadomasochistic appeal of brutal dictators while also eloquently championing love--which, he insisted, was nothing if it did not involve joyful contact with others and humanity at large. Admired all over the world, Fromm continues to inspire with his message of universal brotherhood and quest for lasting peace. The first (...) systematic study of Fromm's influences and achievements, this biography revisits the thinker's most important works, especially _Escape from Freedom_ and _The Art of Loving_, which conveyed important and complex ideas to millions of readers. The volume recounts Fromm's political activism as a founder and major funder of Amnesty International, the National Committee for a Sane Nuclear Policy, and other peace groups. Consulting rare archival materials across the globe, Lawrence J. Friedman reveals Fromm's support for anti-Stalinist democratic movements in Central and Eastern Europe and his efforts to revitalize American democracy. For the first time, readers learn about Fromm's direct contact with high officials in the American government on matters of war and peace while accessing a deeper understanding of his conceptual differences with Freud, his rapport with Neo-Freudians like Karen Horney and Harry Stack Sullivan, and his association with innovative artists, public intellectuals, and world leaders. Friedman elucidates Fromm's key intellectual contributions, especially his innovative concept of "social character," in which social institutions and practices shape the inner psyche, and he clarifies Fromm's conception of love as an acquired skill. Taking full stock of the thinker's historical and global accomplishments, Friedman portrays a man of immense authenticity and spirituality who made life in the twentieth century more humane than it might have been. (shrink)

Jnanasrimitra (975-1025) was regarded by both Buddhists and non-Buddhists as the most important Indian philosopher of his generation. His theory of exclusion combined a philosophy of language with a theory of conceptual content to explore the nature of words and thought. Jnanasrimitra's theory informed much of the work accomplished at Vikramasila, a monastic and educational complex instrumental to the growth of Buddhism. His ideas were also passionately debated among successive Hindu and Jain philosophers. This volume marks the first English translation (...) of Jnanasrimitra's Monograph on Exclusion, a careful, critical investigation into language, perception, and conceptual awareness. Featuring the rival arguments of Buddhist and Hindu intellectuals, among other thinkers, the Monograph reflects more than half a millennium of competing claims while providing an invaluable introduction to a crucial philosopher. Lawrence J. McCrea and Parimal G. Patil familiarize the reader with the author, themes, and topics of the text and situate Jnanasrimitra's findings within his larger intellectual milieu. Their clear, accessible, and accurate translation proves the influence of Jnanasrimitra on the foundations of Buddhist and Indian philosophy. (shrink)

Through his innovative study of language, noted Heidegger scholar Lawrence Hatab offers a proto-phenomenological account of the lived world, the “first” world of factical life, where pre-reflective, immediate disclosiveness precedes and makes possible representational models of language. Common distinctions between mind and world, fact and value, cognition and affect miss the meaning-laden dimension of embodied, practical existence, where language and life are a matter of “dwelling in speech.” In this second volume, Hatab supplements and fortifies his initial analysis by (...) offering a detailed treatment of child development and language acquisition, which exhibit a proto-phenomenological world in the making. He then takes up an in-depth study of the differences between oral and written language (particularly in the ancient Greek world) and how the history of alphabetic literacy shows why Western philosophy came to emphasize objective, representational models of cognition and language, which conceal and pass over the presentational domain of dwelling in speech. Such a study offers significant new angles on the nature of philosophy and language. (shrink)

Nietzsche's On the Genealogy of Morality is a forceful, perplexing, important book, radical in its own time and profoundly influential ever since. This introductory textbook offers a comprehensive, close reading of the entire work, with a section-by-section analysis that also aims to show how the Genealogy holds together as an integrated whole. The Genealogy is helpfully situated within Nietzsche's wider philosophy, and occasional interludes examine supplementary topics that further enhance the reader's understanding of the text. Two chapters examine how the (...) Genealogy relates to standard questions in moral and political philosophy. Written in a clear, accessible style, this book will appeal to students at every level coming to read the Genealogy for the first time, and a wider range of readers will also benefit from nuanced interpretations of controversial elements in Nietzsche's work. (shrink)

For two and a half millennia readers of Aristotle have been struggling to understand just what sort of causation is being attributed to the Prime Unmoved Mover or PM, whether final or efficient, assuming that this supreme being could not be a material cause or even a formal cause of the entire cosmos. Fred Miller entered into this still ongoing debate with a fresh proposal, drawing on an almost incidental remark in GC 1.6.323a25-33 that was later picked up by Philoponus (...) in his commentary on Aristotle’s text. The fundamental question is whether the PM’s causal role is to be restricted to a case of final causation or is there evidence for efficient causation as well? Just how ancient this question of interpretation is can be clearly shown by the following remarks made by Simplicius in the first half of the sixth century in his Neo-Platonist commentary on Phys VIII.6.267b17-26:Simplicius goes on to argue in some detail for this dual picture, primarily because of his harmonizing approach to Plato and Aristotle, but also by referencing some very specific passages in other works—notably Cael, GC, DM—but also Met, albeit only from its first book (1361.11-1363.24). He starts out here by claiming that “[n]o one disputes that Aristotle calls god or the primary mover a final cause” but realizes that showing that the PM is an efficient cause as well needs some textual support, which he dutifully attempts to provide. We will be going over some of the same ground cited here in trying to articulate Aristotle’s conception of divine causation and in particular to decide if Fred Miller’s thoughts about the “untouched toucher” will help us in the overall endeavor to explore Λ.6-10. Since he points out (at p. 278) that the PM could hardly be a material cause or even a formal cause, his framing the issue as to whether the mode of causation here is exclusively efficient or exclusively final, or, on the other hand, both at once, seems very close to how Simplicius set up the problem. Indeed, he cites the same section of Simplicius’s commentary quoted above and finds this ancient perplexity a good jumping off point for his own attempt to shed light on a fundamental issue of interpretation, noting that if we balk at the Neo-Platonic suggestion that Aristotle’s PM “is on a par with Plato’s demiurge,” the question becomes: “in what way is the prime mover supposed to be an efficient cause?” (p. 279). Miller’s novel suggestion is that one way of dealing with this question is the thought that the PM is an “untouched toucher.” It is crucial to his picture that this suggestion is strongly tied to the prospect of finding “a way in which the unmoved mover of the cosmos could be a genuine efficient cause” (p. 287) and not I believe, as W.D. Ross may have held, an efficient cause only by being a final cause. This will become important when we explore what untouched touching would be quite generally, given the emphasis on the psychological dynamics of this sort of affective action as suggested by the everyday examples provided by both Aristotle and Philoponus. (shrink)

This book is a comprehensive exposition of the Transcendental Deduction of the Categories in both editions of Kant’s Critique of Pure Reason.

The principle of double effect has a long history, from scholastic disputations about self-defense and scandal to current debates about terrorism, torture, euthanasia, and abortion. Despite being widely debated, the principle remains poorly understood. In Intention, Character, and Double Effect, Lawrence Masek combines theoretical and applied questions into a systematic defense of the principle that does not depend on appeals to authority or intuitions about cases. Masek argues that actions can be wrong because they corrupt the agent's character and (...) that one must consider the agent's perspective to determine which effects the agent intends. This defense of the principle clears up common confusions and overcomes critics' objections, including confusions about trolley and transplant cases and objections from neuroscience and moral psychology. This book will interest scholars and students in different fields of study, including moral philosophy, action theory, moral theology, and moral psychology. Its discussion of contemporary ethical issues and sparse use of technical jargon make it suitable for undergraduate and graduate courses in applied ethics. The appendix summarizes the main cases that have been used to illustrate or to criticize the principle of double effect. (shrink)

The pull to coordinate with other individuals is fundamental, serving as the basis for our social connectedness to others. Discussed is a dynamical and ecological perspective to joint action, an approach that embeds the individual’s mind in a body and the body in a niche, a physical and social environment. Research on uninstructed coordination of simple incidental rhythmic movement, along with research on goal‐directed, embodied cooperation, is reviewed. Finally, recent research is discussed that extends the coordination and cooperation studies, examining (...) how synchronizing with another, and how emergent social units of perceiving and acting are reflected in people’s feelings of connection to others. (shrink)

Erich Fromm was a political activist, psychologist, psychoanalyst, philosopher, and one of the most important intellectuals of the twentieth century. Known for his theories of personality and political insight, Fromm dissected the sadomasochistic appeal of brutal dictators while also eloquently championing love--which, he insisted, was nothing if it did not involve joyful contact with others and humanity at large. Admired all over the world, Fromm continues to inspire with his message of universal brotherhood and quest for lasting peace. The first (...) systematic study of Fromm's influences and achievements, this biography revisits the thinker's most important works, especially _Escape from Freedom_ and _The Art of Loving_, which conveyed important and complex ideas to millions of readers. The volume recounts Fromm's political activism as a founder and major funder of Amnesty International, the National Committee for a Sane Nuclear Policy, and other peace groups. Consulting rare archival materials across the globe, Lawrence J. Friedman reveals Fromm's support for anti-Stalinist democratic movements in Central and Eastern Europe and his efforts to revitalize American democracy. For the first time, readers learn about Fromm's direct contact with high officials in the American government on matters of war and peace while accessing a deeper understanding of his conceptual differences with Freud, his rapport with Neo-Freudians like Karen Horney and Harry Stack Sullivan, and his association with innovative artists, public intellectuals, and world leaders. Friedman elucidates Fromm's key intellectual contributions, especially his innovative concept of "social character," in which social institutions and practices shape the inner psyche, and he clarifies Fromm's conception of love as an acquired skill. Taking full stock of the thinker's historical and global accomplishments, Friedman portrays a man of immense authenticity and spirituality who made life in the twentieth century more humane than it might have been. (shrink)

This book explores what anyone interested in ethics can draw from Heidegger's thinking. Heidegger argues for the radical finitude of being. But finitude is not only an ontological matter; it is also located in ethical life. Moral matters are responses to finite limit-conditions, and ethics itself is finite in its modes of disclosure, appropriation, and performance. With Heidegger's help, Lawrence Hatab argues that ethics should be understood as the contingent engagement of basic practical questions, such as how should human (...) beings live? (shrink)

Examines the role of indeterminacy in 19th-century British art. Chronicles the irreconcilable tension between the visual and the verbal, beginning in 1806 with Wordsworth's questioning of the essential ground and companionableness of things, and concluding with Hardy's dramatization of the treacherous relationship between the word and the image. Writers revealed here, including Tennyson and Browning, rely in varying degrees on the pictorial to forge analogs as evidence of the kindredness of things. Annotation copyrighted by Book News, Inc., Portland, OR.

The report of the President's Council on Bioethics, Human Cloning and Human Dignity, addresses the central ethical, political, and policy issue in human embryonic stem cell research: the moral status of extracorporeal human embryos. The Council members were in sharp disagreement on this issue and essentially failed to adequately engage and respectfully acknowledge each others' deepest moral concerns, despite their stated commitment to do so. This essay provides a detailed critique of the two extreme views on the Council (i.e., embryos (...) have full moral status or they have none at all) and then gives theoretical grounding for our judgment about the intermediate moral status of embryos. It also supplies an account of how to address profound moral disagreements in the public arena, especially by way of constructing a middle ground that deliberately pays sincere respect to the views of those with whom it has deep disagreements. (shrink)

Hatab's work is more than an interpretative study, inspired by Neitzsche and Heidegger of the historical relationship between myth and philosophy in ancient Greece. Its conclusions go beyond the historical case study, and amount to a defence of the intelligibility of myth against an exclusively rational or objective view of the world.

Lawrence J. Dennis’s intellectual biography of John L. Childs, a leading figure in twentieth-century American educational philosophy between 1930 and 1960, traces Childs’s influence not only on education but also on midcentury politics, economics, and social issues. A disciple of John Dewey and an associate of William Heard Kilpatrick, George S. Counts, Boyd Bode, and other key figures in modern American education, Childs laid the philosophic basis for social reconstruction and became an important contributor to and interpreter of pragmatism (...) as a philosophy of education. Dennis describes how the Christian beliefs so central to Childs as a youth led him as a young man into a decade of YMCA missionary work in China. When he returned to the United States, Childs studied with John Dewey, later coauthoring two chapters of a book with him. Though Childs became a recognized expert on Dewey’s educational theory, he eventually became more of a reconstructionist than his mentor. Dennis carefully recounts Childs’s long association with Dewey as well as his political activities in the American Labor Party, the Liberal Party, and the American Federation of Teachers. He likewise traces the debate about metaphysics, democracy, and indoctrination that ensued among the foremost pragmatists of the day. (shrink)

This volume marks the first English translation of Jnanasrimitra's Monograph on Exclusion, a careful, critical investigation into language, perception, and conceptual awareness.