The apolipoprotein E gene plays an important role in the pathogenesis of Alzheimer's disease , and amyloid plaque comprised mostly of the amyloid-beta peptide ) is one of the major hallmarks of AD. However, the relationship between these two important molecules is poorly understood. We examined how A treatment affects APOE expression in cultured cells and tested the role of the transcription factor NF-B in APOE gene regulation. To delineate NF-B's role, we have characterized a 1098 nucleotide segment containing the (...) 5'-flanking region of the human APOE gene . Sequence analysis of this region suggests the presence of two potential NF-B elements. To demonstrate promoter activity, the region was cloned upstream of a promoterless luciferase gene. This segment was able to drive expression of luciferase in transient transfections of human fetal glial cells. Promoter activity was stimulated twofold by A treatment. Pretreatment with double-stranded DNA decoy oligonucleotides against NF-B reduced A stimulation. Deletion and mutagenetic analyses demonstrated that the distal NF-B element was functional and showed a strong DNA-protein complex band in gel shift analysis, similar to that from control NF-B consensus element. An anti-inflammatory and anti-NF-B drug, sodium salicylate, significantly blocked A-induced APOE promoter function. Our data provide evidence that upregulation of APOE by A in astroglial cells is mediated by an NF-B-element present in the 5'-flanking region of the APOE gene. (shrink)

Medium- and high-spin states of Pr-134 were populated using the Cd-116(Na-23, 5n) reaction and studied with the GAMMASPHERE spectrometer. Several new bands have been found in this nucleus, one of them being linked to the previously observed chiral-candidate twin-band structure. The ground state of Pr-134 could be determined through establishing a level structure that connects the two previously known long-lived isomeric states. Unambiguous spin-parity assignments for the excited states could be performed based on the known 2(-) spin-parity of the ground (...) state combined with the present experimental data. Intrinsic single-particle configurations have been assigned to the newly observed bands on the basis of the measured B(M1)/B(E2) ratios, alignments, band-crossing frequencies, bandhead spins, the observed single-particle configurations in the neighboring nuclei, and taking into account the predictions of total Routhian surface and tilted-axis cranking calculations. (shrink)

Physician-assisted suicide laws in Oregon and Washington require the person's current competency and a prognosis of terminal illness. In The Netherlands voluntariness and unbearable suffering are required for euthanasia. Many people are more concerned about the loss of autonomy and independence in years of severe dementia than about pain and suffering in their last months. To address this concern, people could write advance directives for physician-assisted death in dementia. Should such directives be implemented even though, at the time, the person (...) is no longer competent and would not be either terminally ill or suffering unbearably? We argue that in many cases they should be, and that a sliding scale which considers both autonomy and the capacity for enjoyment provides the best justification for determining when: when written by a previously well-informed and competent person, such a directive gains in authority as the later person's capacities to generate new critical interests and to enjoy life decrease. Such an extension of legalized death assistance is grounded in the same central value of voluntariness that undergirds the current more limited legalization. (shrink)

Almost all jurisdictions where physician-assisted death is legal require that the requesting individual be competent to make medical decisions at time of assistance. The requirement of contemporary competence is intended to ensure that PAD is limited to people who really want to die and have the cognitive ability to make a final choice of such enormous import. Along with terminal illness, defined as prognosis of death within six months, contemporary competence is regarded as an important safeguard against mistake and abuse, (...) arguably the strongest objections to legalizing PAD.The insistence on contemporary competence is problematic. It means that someone who has dementia is ruled out as a candidate for PAD, even if she is terminally ill and suffering terrible and unrelievable pain. It also rules out individuals with strong and unwavering desires not to end their life in dementia. (shrink)

Competent patients have considerable legal authority to control life‐and‐death care. They may refuse medical life support, including medically delivered food and fluids. Even when they are not in need of any life‐saving care, they may expedite death by refusing food and water by mouth—voluntarily stopping eating and drinking, or VSED. Neither right is limited to terminal illness. In addition, in four U.S. states, competent patients, if terminally ill, may obtain lethal drugs for aid‐in‐dying.For people who have dementia and are no (...) longer competent, however, control over the end of life is much less extensive. They may have written a clear advance directive for refusing life‐saving care in specified circumstances yet subsequently find themselves living for years in severe dementia with no need for life‐saving care that could be refused. Chronic progressive dementia is not itself life threatening until its very final stage. Even in jurisdictions that permit active aid‐in‐dying, individuals with advanced dementia are not eligible; they lack the required current competence, and they are seldom deemed terminally ill. As for the right to VSED, its very name—voluntarily stopping eating and drinking—is seen as excluding noncompetent persons.One option for ensuring that one does not live years in severe dementia is to use advance directives to withhold food and water by mouth. The driving element behind VSED is that forcing people to ingest food is as objectionable an intrusion on bodily integrity, privacy, and liberty as imposing unwanted medical treatment. Thus, if incompetent people do not lose their rights to refuse life‐saving treatment, and if people when competent have just as strong a right to VSED as they do to refuse life‐saving treatment, then people do not lose their right to VSED when incompetent either. They only have to exercise it by AD. (shrink)

In the United States, amid the fractious politics of attempting to achieve something close to universal access to basic health care, two impressions are likely to feed skepticism about the status of a right to universal access: the moral principles that underlie any right to universal access may seem incredibly "ideal," not well rooted in the society's actual fabric, and the necessary practical and political attempts to limit the scope of universally accessible care to make its achievement realistic may seem (...) marked less by moral rhyme and reason than by the pull of conflicting interests. I try to directly dispel the first of these impressions and to obliquely question the second. The immense political barriers to .. (shrink)

The case of Mrs A is a provocative example of euthanasia by advance directive to avoid increasingly severe dementia. It is also a ‘perfect storm’ of a disturbing case, revealing both the challenges that can arise with advance euthanasia directives generally and particular issues in the Dutch procedures. Kim, Miller and Dresser have done a distinct service to bioethics in detailing the case, in explaining the basis of the regional euthanasia review committee reprimand of the administering geriatrician and in highlighting (...) some significant deficiencies in Dutch procedures.1 Many readers, after encountering the case, may find themselves sceptical that AEDs can be an ethically viable vehicle for avoiding living into severe dementia. I will argue that caution and care, not resistance to AEDs for dementia, is in order. Real dilemmas of implementation are inherent in advance directives, to be sure, dilemmas that can be aggravated by a patient’s dementia. Yet much can be done in writing an AED to make its implementation in dementia less problematic, and the Dutch emphasis on intolerable suffering as a necessary condition for euthanasia is not the appropriate legal framework. The difficulties in the case begin with the directive itself. Any advance directive, whether for refusing lifesaving treatment or for physician-assisted death, needs to be clear about what is and is not to happen and when. At first Mrs A’s directive seems to provide a trigger point: ‘I want to make use of the legal right to … euthanasia when I am still at all mentally competent and am no longer able to live at home with my husband. I absolutely do not want to be placed in an institution for elderly dementia patients’. In a revision added a year before her death, the time had become ‘whenever I think the time …. (shrink)

In using quality of life as a guide to rationing health services, Oregon laid itself open to charges of bias against the disabled—charges that cannot be dismissed out of hand.

Dual-process models of cognition suggest that there are two types of thought: autonomous Type 1 processes and working memory dependent Type 2 processes that support hypothetical thinking. Models of creative thinking also distinguish between two sets of thinking processes: those involved in the generation of ideas and those involved with their refinement, evaluation, and/or selection. Here we review dual-process models in both these literatures and delineate the similarities and differences. Both generative creative processing and evaluative creative processing involve elements that (...) have been attributed to each of the dual processes of cognition. We explore the notion that creative thinking may rest upon the nature of a shifting process between Type 1 and Type 2 dual processes. We suggest that a synthesis of the evidence bases on dual-process models of cognition and of creative thinking, together with developing time-based approaches to explore the shifting process, could better inform the development of i.. (shrink)

In using quality of life as a guide to rationing health services, Oregon laid itself open to charges of bias against the disabled—charges that cannot be dismissed out of hand.

The Buddhist construct of mindfulness is a central element of mindfulness-based interventions and derives from a systematic phenomenological programme developed over several millennia to investigate subjective experience. Enthusiasm for ?mindfulness? in Western psychological and other science has resulted in proliferation of definitions, operationalizations and self-report inventories that purport to measure mindful awareness as a trait. This paper addresses a number of seemingly intractable issues regarding current attempts to characterize mindfulness and also highlights a number of vulnerabilities in this domain that (...) may lead to denaturing, distortion, dilution or reification of Buddhist constructs related to mindfulness. Enriching positivist Western psychological paradigms with a detailed and complex Buddhist phenomenology of the mind may require greater study and long-term direct practice of insight meditation than is currently common among psychologists and other scientists. Pursuit of such an approach would seem a necessary precondition for attempts to characterize and quantify mindfulness. (shrink)

The book, Against Fairness, by philosopher Stephen T. Asma is reviewed. Concepts of favoritism and justice are explored.

In a recent paper in JME, Shelton and Geppert use an approach by Menzel and Chandler-Cramer to sort out ethical dilemmas about the oral feeding of patients in advanced dementia, ultimately arguing that the usefulness of advance directives about such feeding is highly limited. They misunderstand central aspects of Menzel’s and Chandler-Cramer’s approach, and in making their larger claim that such directives are much less useful than typically presumed, they fail to account for five important elements in writing good directives (...) for dementia and implementing them properly: (1) Directives should be paired with appointment of trusted agents. (2) Appointed agents’ authority can be greatly weakened without advance directives to guide them. (3) Directives’ implementation does not require clinically precise assessment of dementia’s stage. (4) Palliative support is typically required for withholding of oral feeding to be compassionate. (5) The central purpose of stopping feeding is often not the avoidance of suffering but not prolonging unwanted life. (shrink)

Durbin, history and philosophy of science scholar and writer, has created a volume that includes about 100 terms from the natural and social sciences. For each term there is an extended definition and discussion of related philosophic issues. Each entry, about three and one-half pages, also provides a bibliography of some six to a dozen sources. A thorough index includes all terms and people discussed in the entries. This is an excellent source for an entree to the scholarly literature on (...) basic topics such as chance, gender, history, indeterminism, instrumentalism, paradigm, scientific method, and vitalism. Choice This new reference, designed for both students and general readers, provides concise essays on more than one hundred basic core ideas or concepts in the natural and social sciences, supplemented by carefully selected bibliographic listings. Written with a minimum of technical jargon, the essays explore such issues as what it means to be scientific, how theories related to facts in science, and how science compares with other intellectual disciplines. After presenting a clear explanation of the concept, each entry discusses the historical and intellectual context that gave rise to theoretical controversy and assesses the significance of the idea for both the particular discipline and science as a whole. The individual bibliographies will guide the student in tracing the historical development of each subject and investigating its scientific and philosophical aspects in greater detail. Cross referencing and subject indexing are supplied. (shrink)

Volume 20, Issue 8, August 2020, Page 80-82.

Since it may seem strange for a new series to begin with volume 3, a word of explanation is in order. The series, Philosophy and Technology, inaugurated in this form with this volume, is the official publication of the Society for Philosophy & Technology. Approximately one volume each year is tobe published, alternating between proceedings volumes - taken from contributions to biennial international conferences of the Society - and miscellaneous volumes, with roughly the character of a professional society journal. The (...) forerunners of the series in its present form were two proceedings volumes: Philosophy and Technology (1983), edited by Paul T. Durbin and Friedrich Rapp, and Philosophy and Technology //: Information Technology and Computers in Theory and Practice (1986), edited by Carl Mitcham and Alois Huning - both published (as volumes 80 and 90, respectively) in the series, Boston Studies in the Philosophy of Science. The Society for Philosophy & Technology, now more than ten years old, is devoted to the promotion of philosophical schalarship that deals in one way or another with technology and technological society. "Philosophical scholarship" is interpreted broadly as including contribu tions from any and all perspectives; the one requirement is that the schalarship be sound, and all contributions to the series are subject to rigorous blind refereeing. "Technology," the other half of the philos ophy-and-technology pairing, is also construed broadly. (shrink)

We live and thrive in a global society and economy where education and training is essential to a nation’s competitiveness and to the standard of living of its people. Opening the doors of higher or further education beyond the enrollments in elite or select universities has become a greater necessity. This has spawned a movement to develop or expand institutions that are more affordable, accessible, flexible, and tied to business and industry. Take a look at the systems that have been (...) developed in 20 countries worldwide that were designed to meet these needs. Historical development of each system, as well as the strategies for addressing national mandates for preparing a workforce for the global economy, are described throughout each chapter. (shrink)

An assumed core of normative ethical principles may constitute a philosophically proper framework within which public policy should be formulated, but it seldom provides any substantive solutions. To generate public policy on bioethical issues, participants still need to confront underlying philosophical controversies. Professional philosophers' proper role in that process is to clarify major philosophical options, to press wider-ranging concistency questions, and to bring more parties into the philosophical debate itself by arguing for particular substantive claims. Though questions of fact that (...) mediate final policy conclusions frequently fall outside philosophical competence, one sort of fact, lack of political support, should seldom cause philosophers to stand aside; philosophers still have an important role as critics of culture, politics, and profession. They have no authority, however, on even the philosophical presuppositions of public policy. Keywords: bioethics, philosophy, public policy CiteULike Connotea Del.icio.us What's this? (shrink)

A number of themes have been on my mind in recent months, and I have made them centerpieces of a number of things I have written lately. In a Ubiquity essay Durbin (ACM Ubiquity 8(45):26, 2007a), I said that I am happy that there are computer professionals who are activists, joining with others to solve the technosocial problems that vex our society, including problems of the computer and information professions. I here moved beyond that to make a new claim about (...) needed changes. (shrink)

Method descriptive frameworks, and a practical program for philosophy of technology; The University of Delaware Conference, 1975; Review and bibliography; European contributions; Conference Papers, 1976-1977; Historico-philosophical studies.