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)

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)

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)

International array of contributors, bringing together both traditional and more recent approaches to provide valuable insights into the poets’ use of language.Covers authors from Lucilius to Juvenal.Of the peoples of ancient Italy, only the Romans committed newly composed poems to writing, and for 250 years Latin-speakers developed an impressive verse literature.The language had traditional resources of high style, e.g., alliteration, lexical and morphological archaism or grecism, and of course metaphor and word order; and there were also less obvious resources in (...) the technical vocabularies of law, philosophy and medicine.The essays in this volume show how the poets in the classical period combined these elements, and so created a poetic medium that could comprehend satire, invective, erotic elegy, drama, lyric, and the grandest heroic epos. (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)

Indian philosophical thought has been deeply metaphysical, and it is no surprise that, faced with the anti-metaphysical thrust of contemporary philosophy, one of the issues uppermost in the minds of Indian thinkers is the question of the possibility of metaphysics. In recent philosophical literature, two tendencies are discernible: an attempt to defend metaphysics in the traditional grand style, and a concern with the idea of descriptive metaphysics as an alternative. For the former, we may turn to Kalidas Bhattacharyya and J. (...) N. Chubb; for the latter to J. N. Mohanty and S. N. Ganguly. (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)

Renowned philosopher J. N. Mohanty examines the range of Indian philosophy from the Sutra period through the 17th century Navya Nyaya. Instead of concentrating on the different systems, he focuses on the major concepts and problems dealt with in Indian philosophy. The book includes discussions of Indian ethics and social philosophy, as well as of Indian law and aesthetics.

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)

It was in my view a very important thing that took place when, at the beginning of the Third Century A.D., Ammonius Saccas began his exegeses of Plato, basing himself on the important assumption, much more true than false, of a profound homodoxy or agreement of opinion between Plato and Aristotle. This work involved an attempt to see Plato as something more than a brilliant virtuoso of inconclusive, often fallacious argument—a role only admirable in Socrates on account of his existentially (...) revealed conviction of the impossibility of defining the virtues in a clear-cut manner, or apart from one another, or from the critical activity which redefines them unendingly—and which also sees Plato as something more than an ancestor of the Pythagorean mystagogues who dispensed a way of life to those doomed to live it under the Caesars, or of philosophical littérateurs of Ciceronian and similar types. It represented an attempt to make serious philosophical sense of Plato as a thinker desirous of determining what primarily is, and what only is in some secondary or derivative sense, and how the various grades and senses of being may be accommodated to one another and to the human soul with its profound need to understand and love. And it necessarily sought support in such texts as the Phaedo, the Phaedrus, the Symposium, the Republic, the Timaeus, and the Letters, as well as in a suitably interpreted Sophist and Parmenides, and hardly at all in such brilliant recrudescences of Socratic inconclusiveness as the latter half of the Theaetetus. And it incorporated strands from the pre-Socratics and from Aristotle because these were seen as either leading up to, or continuing, the serious Platonic effort. I am myself disposed to ascribe this new wave of Platonic deepening to Ammonius rather than Plotinus, since there is singularly little development of doctrine in the smoothly written Enneads, and since Plotinus only began to publish his doctrine when his two fellow pupils, Erennius and Origen, had started to divulge what their Master had taught them. (shrink)

The aim of this paper is to give a characterisation of religion and the Religious Spirit, basing itself on the Platonic assumption that there are Forms, salient jewels of simplicity and affinity, to be dug out from the soil of vague experience and cut clear from the confusedly shifting patterns of usage, which will give us conceptual mastery over the changeable detail in a given sector. It will further be Platonic in that it will not seek to discount the deep (...) gulfs between the species into which religion qua genus divides itself, i.e. its theistic, polytheistic and atheistic subvarieties, taking it to be of the essence of a true genus to extend itself over mutually exclusive species, only being what it is by including in its sense the alternatives which are thus mutually exclusive. And my treatment will be Platonic, thirdly, in that it will endeavour to delimit the Religious Spirit by, on the one hand, setting it over against what it excludes, all purely this-world talk and life which is quite irreligious, and by, on the other hand, opposing it to forms of talk and life which fall short of it in various ways or which deviate from it variously, thereby likewise contributing to our understanding of what it is. The practice of Plato, which could study the deviations from his ideal city in order to confirm his notion of its structure and excellence, and which also paired every ideal pattern with its opposite— piety with impiety, justice with self-interested tyranny, etc.—is plainly one to be followed: Plato, as we know from a citation from his contemporary Hermodorus in one of the Aristotelian commentators, always set beside the ‘in itself’ of the pure Form the deviant and the wholly negative which were nonetheless part of its sense. Religion will therefore stand before us as a target that it is possible to fall short of or miss altogether as well as to hit squarely, and we shall try by a series of glancing darts to end by hitting it squarely. (shrink)