Although activated spinal cord glia contribute importantly to neuropathic pain, how nerve injury activates glia remains controversial. It has recently been proposed, on the basis of genetic approaches, that toll-like receptor 4 may be a key receptor for initiating microglial activation following L5 spinal nerve injury. The present studies extend this idea pharmacologically by showing that TLR4 is key for maintaining neuropathic pain following sciatic nerve chronic constriction injury. Established neuropathic pain was reversed by intrathecally delivered TLR4 receptor antagonists derived (...) from lipopolysaccharide. Additionally, -naltrexone, -naloxone, and -naloxone, which we show here to be TLR4 antagonists in vitro on both stably transfected HEK293-TLR4 and microglial cell lines, suppressed neuropathic pain with complete reversal upon chronic infusion. Immunohistochemical analyses of spinal cords following chronic infusion revealed suppression of CCI-induced microglial activation by -naloxone and -naloxone, paralleling reversal of neuropathic pain. Together, these CCI data support the conclusion that neuron-to-glia signaling through TLR4 is important not only for initiating neuropathic pain, as suggested previously, but also for maintaining established neuropathic pain. Furthermore, these studies suggest that the novel TLR4 antagonists -naloxone and -naloxone can each fully reverse established neuropathic pain upon multi-day administration. This finding with -naloxone is of potential clinical relevance. This is because -naloxone is an antagonist that is inactive at the -opioid selective receptors on neurons that produce analgesia. Thus, these data suggest that -opioid antagonists such as -naloxone may be useful clinically to suppress glial activation, yet -opioid agonists suppress pain. (shrink)

BackgroundFear of cancer recurrence is an important cause of suffering for cancer survivors, and both empirical evidence and theoretical models suggest that prognostic uncertainty plays a causal role in its development. However, the relationship between prognostic uncertainty and FCR is incompletely understood.ObjectiveTo explore the relationship between prognostic uncertainty and FCR among patients with ovarian cancer.DesignA qualitative study was conducted utilizing individual in-depth interviews with a convenience sample of patients with epithelial ovarian cancer who had completed first-line treatment with surgery and/or (...) chemotherapy. Semi-structured interviews explored participants’ understanding of their prognosis; experiences, preferences, and attitudes regarding prognostic information; and strategies for coping with prognostic uncertainty. Inductive qualitative analysis and line-by-line software-assisted coding of interview transcripts was conducted to identify key themes and generate theoretical insights on the relationship between prognostic uncertainty and FCR.ResultsThe study sample consisted of 21 participants, nearly all of whom reported experiencing significant FCR, which they traced to an awareness of the possibility of a bad outcome. Some participants valued and pursued prognostic information as a means of coping with this awareness, suggesting that prognostic uncertainty causes FCR. However, most participants acknowledged fundamental limits to both the certainty and value of prognostic information, and engaged in various strategies aimed not at reducing but constructing and maintaining prognostic uncertainty as a means of sustaining hope in the possibility of a good outcome. Participants’ comments suggested that prognostic uncertainty, fear, and hope are connected by complex, bi-directional causal pathways mediated by processes that allow patients to cope with, construct, and maintain their uncertainty. A provisional dual-process theoretical model was developed to capture these pathways.ConclusionAmong patients with OC, prognostic uncertainty is both a cause and an effect of FCR—a fear-inducing stimulus and a hope-sustaining response constructed and maintained through various strategies. More work is needed to elucidate the relationships between prognostic uncertainty, fear, and hope, to validate and refine our theoretical model, and to develop interventions to help patients with OC and other serious illnesses to achieve an optimal balance between these states. (shrink)

J. N. Adams, Michael Lapidge, and Tobias Reinhardt: IntroductionJ. H. W. Penney: Connections in Archaic Latin ProseJ. Briscoe: Language and Style of the Fragmentary Republican HistoriansJ. N. Adams: The Bellum AfricumChristina Shuttleworth Kraus: Hair, Hegemony, and Historiography: Caesar's Style and its Earliest CriticsJ. G. F. Powell: Cicero's Adaptation of Legal Latin in the De legibusTobias Reinhardt: Language of Epicureanism in Cicero: The Case of AtomismG. O. Hutchinson: Pope's Spider and Cicero's WritingR. G. Mayer: The Impracticability of 'Kunstprosa'H. M. Hine: (...) Poetic Influence on Prose: The Case of the Younger SenecaHarm Pinkster: The Language of Pliny the ElderD. R. Russell: Omisso speciosiore stili genereS. J. Harrison: The Poetics of Fiction: Poetic Influence on the Languages of Apuleius' MetamorphosesD. R. Langslow: 'Langues réduites au lexique'? The Languages of Latin Technical ProseDanuta Shanzer: of Tours and Poetry: Prose into Verse and Verse into ProseMichael Lapidge: Poeticism in Pre-Conquest Anglo-Latin ProseRichard Sharpe: The Varieties of Bede's ProseCarlotta Dionisotti: Translator's LatinWalter Berschin: Realistic Writing in the Tenth Century: : Gerhard of Ausburg's Vita S. UodalriciR. M. Thomson: William of Malmesbury and the Latin Classics RevisitedGiovanni Orlandi: Metrical and Rhythmical Clausulae in Medieval Latin Prose: Some Aspects and Problems. (shrink)

Professor Lewis and I have some important differences of opinion regarding the identity and distinctness of conscious persons, which it will be well to try to clarify on the present occasion, first of all by enumerating a number of points on which we are, I think, in agreement. Both of us believe in the existence of individual persons, each of whom can be said to live in a ‘world’ of his own intentional objectivity, a world ‘as it is for him’, (...) which differs in a considerable extent, both in content and emphasis, from the world as it is for anyone else. Both of us further believe that all these intentionally objective worlds for a large part coincide in content, and are in fact excerpted from a more comprehensive real world which is common to us all, and which, in addition to in some sense including all such intentionally objective worlds, also includes many real material objects which exist regardless of our intentionality, and which further includes our own material bodies, which appear in so central a manner in each of our intentionally objective worlds. Both of us believe in matter as a transcendent reality, as well as an intentional object, and are content to accept the dicta of science as to the most probable view of its structure. We are in fact quite Cartesian and Lockean in our belief in the primary and secondary qualities of matter. We believe further that our intentional subjectivity is geared causally into our material objectivity, and that the gearing takes place, in some inscrutable manner, in our nervous systems. We both also believe that our intentional subjectivity transcends bodily mechanisms and instrumentalities, and can be liberated from the latter, but that, when thus liberated, our subjectivity may still affect some sort of an intentionally objective material body such as we wear in dreams, a body in which it will manifest itself to itself and to others much as we do in our dreams and fantasies. (shrink)

All recent memory theories of hippocampal function have incorporated the idea that the hippocampus is required to process items only of some qualitatively specifiahle kind, and is not required to process items of some complementary set. In contrast, it is now proposed that the hippocampus is needed to process stimuli of all kinds, but only when there is a need to associate those stimuli with other events that are temporally discontiguous. In order to form or use temporally discontiguous associations, it (...) is essential to maintain some memory of the first component until the second component has occurred. When the temporal gap to he spanned is small, and the number of items to be temporarily retained is low, a limited-capacity, short-term store is sufficient to allow associations to be formed. Such a store is presumed to operate in parallel with the hippocampus in normal animals. Hippocampal damage disrupts a much higher-capacity store that has a slower decay rate, and so leaves animals with only a very limited ability to form temporally discontiguous associations. Hippocampal damage, however, is not held to affect the long-term storage of associations of any kind, if they can be formed. Analyses of both new and existing data are presented to show that by classifying tasks in terms of the need to use a temporary memory store to retain temporally discontiguous information one can cut right across existing classifications as well as achieve a better fit to the data. The hippocampus thus seems best described as a high-capacity, intermediate-term memory store. (shrink)

A collection of readings which provides managers and students with a compilation of articles illustrating the application of operations research to aid in managerial decision making.

The degrees of formality into which speech can be graded are in no sphere more obvious than in expressions of address and third-person reference. Methods of naming vary according to many factors: the formality of the circumstances in which naming takes place, the nature of the subject under discussion, and the ages, sex, and relative status of the speaker and addressee. Conventions of naming sometimes reflect the rigidity or otherwise of social divisions. In some societies or circles address between superior (...) and subordinate is non-reciprocal: the speaker with the greater prestige will adopt one form of address, the subordinate another. In other societies when unequals address each other both may use the same formal method of address: the difference of prestige is not explicitly acknowledged. (shrink)

Aims. Currently, methylphenidate (MPH, trade name Ritalin) is the most widely prescribed medication for attention deficit/hyperactivity disorder (ADHD). We examined the ability of repeated MPH administration to produce a sensitized appetitive eagerness type response in laboratory rats, as indexed by 50-kHz ultrasonic vocalizations (50-kHz USVs). We also examined the ability of MPH to reduce play behavior in rats which may be partially implicated in the clinical efficacy of MPH in ADHD. Design. 56 adolescent rats received injections of either 5.0 mg/kg (...) MPH, or vehicle each day for 8 consecutive days, and a week later received a challenge injection of either MPH or vehicle. Measurements. Both play behavior (pins) and 50-kHz USVs were recorded after each drug or vehicle administration. Results. MPH challenge produced a substantial 73% reduction in play behavior during the initial treatment phase, and during the last test (1 week post drug), 50-kHz USVs were elevated approximately threefold only in animals with previous MPH experience. Conclusions. These data suggest that MPH treatment may lead to psychostimulant sensitization in young animals, perhaps by increasing future drug-seeking tendencies due to an elevated eagerness for positive incentives. Further, we hypothesize that MPH may be reducing ADHD symptoms, in part, by blocking playful tendencies, whose neuro-maturational and psychological functions remain to be adequately characterized. (shrink)

First published in 2002. Routledge is an imprint of Taylor & Francis, an informa company.

This volume is a collection of my essays on philosophy of logic from a phenomenological perspective. They deal with the four kinds of logic I have been concerned with: formal logic, transcendental logic, speculative logic and hermeneutic logic. Of these, only one, the essay on Hegel, touches upon 'speculative logic', and two, those on Heidegger and Konig, are concerned with hermeneutic logic. The rest have to do with Husser! and Kant. I have not tried to show that the four logics (...) are compatible. I believe, they are--once they are given a phenomenological underpinning. The original plan of writing an Introduction in which the issues would have to be formulated, developed and brought together, was abandoned in favor of writing an Introductory Essay on the 'origin'- in the phenomenological sense -of logic. J.N.M. Philadelphia INTRODUCTION: THE ORIGIN OF LOGIC The question of the origin of logic may pertain to historical origin (When did it all begin? Who founded the science of logic?), psychological origin (When, in the course of its mental development, does the child learn logical operations?), cultural origin (What cultural - theological, metaphysical and linguisti- conditions make such a discipline as logic possible?), or transcendental constitutive origin (What sorts of acts and/or practices make logic possible?). (shrink)

This is a very valuable study of the relations, as regards affinity and mutual influence, of two major philosophers who are now more and more being assessed at what we may hold to be their immense true worth. Both were philosophers who brought a form of Platonic realism, quite out of fashion at the time, into their interpretation of logical and mathematical concepts and principles, and who moved away from the psychologistic approaches which see such concepts and principles merely as (...) a set of forms and rules which govern our actual human thinking and its linguistic expression, and whose normative or standard-fixing aspects have their roots in the mere way in which our minds work and the mere ways in which the actual world fits in with their workings. But both thinkers, at a higher level, moved on to a view in which something like a transcendental Kantian Reason served as the ultimate foundation both of the forms and guiding principles of referential thought and of the factual empirical world whose structure this thought tries to encompass and to articulate. Both philosophers further seek in the mediating concept of Sinn or sense, as closely connected with the uses of language as with the objective matters with which language deals, the link between thought and other subjective orientations, on the one hand, and the various objective matters with which thought and language are concerned. Both thinkers, however, display great obscurities at certain points in the working out of their thoughts, by which obscurities their relation to one another is also at certain points rendered obscure. (shrink)

It is claimed that cantor had the technical apparatus available to derive russell's paradox some ten years before russell's discovery.

Excerpt from A Primer of Right and Wrong: For Young People in Schools and Families But we can be puppet-like Self-mastery never impossible Habits, and their power Habit-making in childhood Habit-cultivation. About the Publisher Forgotten Books publishes hundreds of thousands of rare and classic books. Find more at www.forgottenbooks.com This book is a reproduction of an important historical work. Forgotten Books uses state-of-the-art technology to digitally reconstruct the work, preserving the original format whilst repairing imperfections present in the aged copy. (...) In rare cases, an imperfection in the original, such as a blemish or missing page, may be replicated in our edition. We do, however, repair the vast majority of imperfections successfully; any imperfections that remain are intentionally left to preserve the state of such historical works. (shrink)

On the ethics of extending human life: healthy people have a right to carry on livingHumanity has long demonstrated a paradoxical ambivalence concerning the extension of a healthy human lifespan. Modest health extension has been universally sought, whereas extreme health extension has been regarded as a snare and delusion—a dream beyond all others at first blush, but actually something we are better off without. The prevailing pace of biotechnological progress is bringing ever closer the day when humanity will be able (...) to act on the latter view by rejecting a clear and present opportunity for much longer healthy lives. Indeed, some biogerontologists contend that that day has already arrived, to the extent that our hesitation in embarking on a vigorous “war on ageing” is already delaying the point at which a cure for ageing will be developed. Here I consider whether our present caution concerning the wisdom of truly curing ageing is likely to survive the increased scrutiny that it will receive in coming years as a result of these technical advances. I conclude that it will not, because of its irreconcilability with values that are more deeply held by the large majority of humanity than any values that argue against the quest for a cure. I further conclude that all the major current reasons given for not curing ageing are mere crutches to help us cope with the immutability of ageing that we have been brought up to accept. Our failure to set aside such irrationality is already shortening potential longevity—quite probably of those already alive today—to a staggering degree. Once we realise this, our determination to consign human ageing to history will be second …. (shrink)

ABSTRACT:This essay argues for the importance of formalizing public engagement efforts around bioethics as something we might call "bioethics communication," and it outlines the Johns Hopkins Berman Institute of Bioethics' plans for engaging in this effort. Because science is complex and difficult to explain to nonexperts, the field of science communication has arisen to meet this need. The field involves both a practice and a subject of empirical research. Like science, bioethics is also complex and difficult to explain, which is (...) why the world needs bioethics communication. The authors are engaged in a brand-new effort to establish the sort of public bioethics efforts that would constitute bioethics communication, through a program which they call the Dracopoulos-Bloomberg iDeas Lab. The authors invite colleagues to experiment and learn with them as they invest in the development of bioethics communicators and their products. (shrink)

It would be a mistake to attempt to identify in modern terms the disease of Galerius described so graphically by Lactantius, Mort. 33. Consumption by lice or worms, if not genital ‘gangrene’, was a typical end for a tyrant or the impious, and there must be an element of literary exaggeration in Lactantius' account. But whatever one makes of the nature of the illness, Lactantius did set out to give the passage a scientific plausibility by his use of technical medical (...) phraseology, and by an allusion to a medical theory at 33.7. Recognition of this theory allows one to settle the text at one point, where editors have failed to agree. There is also a second place in the chapter where familiarity with medical Latin points one towards the solution of a textual problem. (shrink)