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)

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

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)

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)

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)

The problems of internationalism often look different and require different solutions depending on one’s particular cultural standpoint. Contemporary Indian philosophers find that their philosophical efforts have long been too much oriented to the West, and that what Indian philosophy now needs is less international influence and more rootedness in their own rich tradition. This is needed for a more balanced international dialogue. The goal of internationalism in philosophy is not to bring into being a world‐philosophy, but a global conversation on (...) philosophical problems that is not inhibited by differing approaches. (shrink)

The demonstration by E. Wölfflin that between theHistoriesandAnnalsTacitus progressed towards a more archaic and artificial style is well known. From the outset Tacitus adhered to the traditional Roman view that history should be composed in an archaic language remote from everyday usage ; but he was apparently at first not fully aware of the possibilities of the archaizing style. New archaisms and artificial usages suggested themselves as he advanced ; and others, which he had used sporadically even early in theHistories, (...) were allowed to oust ordinary alternatives completely. (shrink)

In his award-winning book _The Philosophy of Edmund Husserl: A Historical Development_, J. N. Mohanty charted Husserl's philosophical development from the young man's earliest studies—informed by his work as a mathematician—to the publication of his _Ideas_ in 1913. In this welcome new volume, the author takes up the final decades of Husserl's life, addressing the work of his Freiburg period, from 1916 until his death in 1938. As in his earlier work, Mohanty here offers close readings of Husserl's main texts (...) accompanied by accurate summaries, informative commentaries, and original analyses. This book, along with its companion volume, completes the most up-to-date, well-informed, and comprehensive account ever written on Husserl's phenomenological philosophy and its development. (shrink)