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)

The subjective character of a given experience leaves open the question of its precise status. If it looks to a subject K as if there is an object of a kind F in front of him, the experience he is having could be veridical, or hallucinatory. Advocates of the Causal Theory of perception (whom I shall call.

Background Escalating levels of obesity place enormous and growing demands on Health care provision in the (U.K.) United Kingdom. Resources are limited with increasing and competing demands upon them. Ethical considerations underpin clinical decision making generally, but there is limited evidence regarding the relationship between these variables particularly in terms of treating individuals with obesity. Research aim To investigate the views of National Health Service (NHS) clinicians on navigating the ethical challenges and decision making associated with obesity management in adults (...) with chronic illness. Research design A cross-sectional, multi-site survey distributed electronically. Participants A consensus sample of nurses, doctors, dietitians and final year students in two NHS Trusts and two Universities. Ethical considerations Ethical and governance approvals obtained from a National Ethics Committee (11NIR035), two universities and two teaching hospitals. Results Of the total ( n = 395) participants, the majority were nurses (48%), female (79%) and qualified clinicians (59%). Participants strongly considered the individual to have primary responsibility for a healthy weight and an obligation to attempt to maintain that healthy weight if they wish to access NHS care. Yet two thirds would not withhold treatment for patients with obesity. Discussion While clinicians were clear about patient responsibility and obligations, the majority prioritised their duty of care and would not invoke a utilitarian approach to decision making. This may reflect awareness of obesity as a multi-faceted entity, with responsibility for support and management shared amongst society in general. Conclusions The attitudes of this sample of clinicians complemented the concept of the health service as being built on a principle of community, with each treated according to their need. However limited resources challenge the concept of needs-based decisions consequently societal engagement is necessary to agree a pragmatic way forward. (shrink)

I argue that popular understandings of white nationalist double speak strategies do not fully represent the practice of these strategies, and identify a linguistic tactic used by white nationalists that I call sugar-coating. Sugar-coating works by packing an otherwise unacceptable utterance together with some kind of reward, thereby promoting uptake. I contrast this with existing notions of double speak, such as figleaves (Saul 2017, 2021), dogwhistles (Haney-López 2014), and bullshit (Kenyon and Saul 2022). I argue that sugar-coating more accurately reflects (...) the practice of white nationalist recruitment rhetoric, as described in the Daily Stormer Style Guide. (shrink)

For readers of Women in Clothes, a philosophical guide to fashion. We all get dressed. But how often do we pause to think about the place of our clothes in our world? What unconscious thoughts do we express when we dress every day? Can a philosophy of living be wrapped up in a winter coat? Can we see clothes not as objects, but as ideas? Dressed is the thinking person's book about clothes, exploring these questions by ranging freely from suits (...) to suitcases, from Marx's coat to Madame X's gown. Through literature and art, film and philosophy, philosopher Shahidha Bari unveils the surprising and subconscious ways what we wear communicates with us, about us, and for us. Dressed is about the hidden power of clothes in our culture and our daily lives, addressing the deepest questions of who we are, how we frame ourselves, and how we choose to face the world. (shrink)

Medical science brings innovations in patient care at an astounding pace today - new chemotherapeutic agents, coated stents, and minimally invasive surgery are just few recent examples. For physicians, though, the specter of malpractice liability can overshadow the marvel of practicing in this era. Many physicians are working in a volatile liability environment; they face spiraling costs for malpractice insurance, have difficulties purchasing liability coverage at any price, and see record payouts in a growing number of claims against their colleagues. (...) The American Medical Association has declared that at least 20 states are currently in a malpractice “crisis,” with another 24 states showing early signs of an impending crisis.There have been two comparable periods of instability in the last thirty years, but these predecessor crises differ from the current one in important ways. First, while physicians mainly experienced dwindling options for obtaining coverage in the mid-1970s and exorbitant prices in the mid-1980s, the current crisis appears to have elements of both availability and affordability. (shrink)

Medical science brings innovations in patient care at an astounding pace today - new chemotherapeutic agents, coated stents, and minimally invasive surgery are just few recent examples. For physicians, though, the specter of malpractice liability can overshadow the marvel of practicing in this era. Many physicians are working in a volatile liability environment; they face spiraling costs for malpractice insurance, have difficulties purchasing liability coverage at any price, and see record payouts in a growing number of claims against their colleagues. (...) The American Medical Association has declared that at least 20 states are currently in a malpractice “crisis,” with another 24 states showing early signs of an impending crisis.There have been two comparable periods of instability in the last thirty years, but these predecessor crises differ from the current one in important ways. First, while physicians mainly experienced dwindling options for obtaining coverage in the mid-1970s and exorbitant prices in the mid-1980s, the current crisis appears to have elements of both availability and affordability. (shrink)

These penetrating metaphysical and spiritual teachings cross the divides of culture and time, providing unexpectedly modern insight.

Plato’s references to Empedocles in the myth of the Statesman perform a crucial role in the overarching political argument of the dialogue. Empedocles conceives of the cosmos as structured like a democracy, where the constituent powers ‘rule in turn’, sharing the offices of rulership equally via a cyclical exchange of power. In a complex act of philosophical appropriation, Plato takes up Empedocles’ cosmic cycles of rule in order to ‘correct’ them: instead of a democracy in which rule is shared cyclically (...) amongst equal constituents, Plato’s cosmos undergoes cycles of the presence and absence of a single cosmic monarch who possesses ‘kingly epistēmē’. By means of a revision of Empedocles’ democratic cosmology, Plato’s richly woven myth is designed precisely to reject the appropriateness of democracy as a form of human political association and legitimate monarchy in its stead. (shrink)

What is it to blame someone, and when are would-be blamers in a position to do so? What function does blame serve in our lives, and is it a valuable way of relating to one another? The essays in this volume explore answers to these and related questions.

History presents us with a unity which is also a plurality. Both materialism and idealism subordinate the plurality to the unity, interpreting the particular either in terms of racial and social laws, or in terms of a unitary Idea or Spirit; and both, when developed to their logical conclusion, lead to a denial of significance to individual personality. According to the opposite point of view ‘objective spirit’ and economic ‘laws’ are equally abstractions of an individual’s mind, whose existence as a (...) separately willing and experiencing self is prior and irresolvable. The problem is then to account for the unity of history in terms of individuals who are historically related but essentially separate. (shrink)

Last year the B.B.C. arranged for certain eminent men to broadcast their Points of View to the public. The result was a most interesting series of talks; but for the sceptical philosopher the series was chiefly entertaining for its brilliantly illustrating the old tag: quot homines, tot sententiæ. One was struck not merely by the discrepancy of opinion, but by how each speaker was ‘true to type': the biologist, the physicist with a taste for spiritualism, the Christian Platonist, and the (...) rest—each spoke his part and told of a world built according to his own particular measuring-rod. (shrink)

The issue of what distinguishes systems which have original intentionalityfrom those which do not has been brought into sharp focus by Saul Kripke inhis discussion of the sceptical paradox he attributes to Wittgenstein.In this paper I defend a sophisticated version of the dispositionalistaccount of meaning against the principal objection raised by Kripke in hisattack on dispositional views. I argue that the objection put by the sceptic,to the effect that the dispositionalist cannot give a satisfactory account ofnormativity and mistake, in fact (...) comprises a number of distinct lines ofargument, all of which can be satisfactorily answered by the dispositionalist.Two central problems raised by the sceptic consist in explaining (1) theextension of the term which a subject uses, and (2) the fact that the subjectintends to use the term with that extension, and is thus justified in her use.I adapt a suggestion of Blackburn's, that the extension of a word is fixed bya person's extended first-order dispositions to use it, and suggest that thereis no coherent possibility of a subject being disposed to makesystematic mistakes in connection with many ordinary words; the scepticalproblem does not apply in the same way throughout language. It is furtherargued that an account which appeals to a subject's second-orderdispositions to maintain a consistent pattern of extended first-orderdispositions to use words is able to provide a naturalistic basis to answerthe normative questions about justification of use. Three other variants ofthe mistake objection which are also revealed by a careful examination ofKripke's arguments are distinguished and it is shown that the dispositionalisthas adequate resources to meet them.The appeal to second-order dispositions provides a principled way ofdistinguishing between those systems (animal or machine) which have originalintentionality, and those which do not. (shrink)

According to the powerful qualities view, properties are both powerful and qualitative. Indeed, on this view the powerfulness of a property is identical to its qualitativity. Proponents claim that this view provides an attractive alternative to both the view that properties are pure powers and the view that they are pure qualities. It remains unclear, however, whether the claimed identity between powerfulness and qualitativity can be made coherent in a way that allows the powerful qualities view to constitute this sort (...) of alternative. I argue here that this can be done, given a particular conception of both the qualitativity and powerfulness of properties. On this conception, a property is qualitative just in the sense that its essence is fixed independently of any distinct properties, and it is powerful just if its essence grounds its dispositional role. (shrink)

Epistemic akrasia arises when one holds a belief even though one judges it to be irrational or unjustified. While there is some debate about whether epistemic akrasia is possible, this paper will assume for the sake of argument that it is in order to consider whether it can be rational. The paper will show that it can. More precisely, cases can arise in which both the belief one judges to be irrational and one’s judgment of it are epistemically rational in (...) the sense that both are supported by sufficient evidence. (shrink)

This is the first chapter to our edited collection of essays on the nature and ethics of blame. In this chapter we introduce the reader to contemporary discussions about blame and its relationship to other issues (e.g. free will and moral responsibility), and we situate the essays in this volume with respect to those discussions.

Blame is usually discussed in the context of the free will problem, but recently moral philosophers have begun to examine it on its own terms. If, as many suppose, free will is to be understood as the control relevant to moral responsibility, and moral responsibility is to be understood in terms of whether blame is appropriate, then an independent inquiry into the nature and ethics of blame will be essential to solving (and, perhaps, even fully understanding) the free will problem. (...) In this article we first survey and categorize recent accounts of the nature of blame – is it action, belief, emotion, desire, or something else? – and then we look at several proposed requirements on appropriate blame that look beyond the transgressor himself, considerations that will form part of a full account of the ethics of blame. (shrink)

In this paper we discuss studies that show that most people do not find determinism to be incompatible with free will and moral responsibility if determinism is described in a way that does not suggest mechanistic reductionism. However, if determinism is described in a way that suggests reductionism, that leads people to interpret it as threatening to free will and responsibility. We discuss the implications of these results for the philosophical debates about free will, moral responsibility, and determinism.

The question in philosophy of whether History is a Science is rather like the question in Politics of the expediency of a Channel Tunnel: it is one which provides a perennial subject for debate, there is no indication that it will ever be decided one way or the other, and it does not after all seem to matter much even if it never is decided; we can get along well enough by neglecting it altogether. One might argue indeed that the (...) dispute is not much more than a matter of words, of the intension and extension of terms. It is evident that the method and aim of the historian differ widely from those of the physicist, and on the other hand resemble closely those of the geologist. Why trouble to go splitting hairs? (shrink)

Ordinarily, we take moral responsibility to come in degrees. Despite this commonplace, theories of moral responsibility have focused on the minimum threshold conditions under which agents are morally responsible. But this cannot account for our practices of holding agents to be more or less responsible. In this paper we remedy this omission. More specifically, we extend an account of reasons-responsiveness due to John Martin Fischer and Mark Ravizza according to which an agent is morally responsible only if she is appropriately (...) receptive to and reactive to reasons for action. Building on this, we claim that the degree to which an agent is responsible will depend on the degree to which she is able to recognize and react to reasons. To analyze this, we appeal to relations of comparative similarity between possible worlds, arguing that the degree to which an agent is reasons-reactive depends on the nearest possible world in which given sufficient reason to do otherwise, she does so. Similarly, we argue that the degree to which an agent is reasons-receptive will depend on the intelligibility of her patterned recognition of reasons. By extending an account of reasons-responsiveness in these ways, we are able to rationalize our practice of judging people to be more or less responsible. (shrink)

I defend a new account of constitutive essence on which an entity’s constitutively essential properties are its most fundamental, nontrivial necessary properties. I argue that this account accommodates the Finean counterexamples to classic modalism about essence, provides an independently plausible account of constitutive essence, and does not run into clear counterexamples. I conclude that this theory provides a promising way forward for attempts to produce an adequate nonprimitivist, modalist account of essence. As both triviality and fundamentality in the account are (...) understood in terms of grounding, the theory also potentially has important implications for the relation between essence and grounding. (shrink)

If one takes a course in philosophy to-day at a British university, a discreet silence is usually observed about existentialism. Often the professors understand little of its methods or its doctrine. If their excuse in part is the inaccessibility in English of standard existentialist texts, it is true also that philosophers trained in the “critical philosophy” now in vogue feel a certain aversion to existentialism or, at all events, to the notion they have formed of it. If Christianity was a (...) scandal to the Greeks and remains a scandal, as Dr. Brunner has recently told us, to contemporary humanists, existentialism is a scandal to the positivists. The latter are aware that the existentialists habitually trespass in the fields of religion, ethics, aesthetics and psychology, fields which, on the positivist view, should be reserved to other disciplines than philosophy, which has its own distinctive subject-matter and approach. They know that certain existentialists, notably Heidegger, provide a happy hunting ground for examples of “metaphysics.” They have heard that existentialism has sought to turn the tables on positivism by accusing it, if not of metaphysics, at all events of a barrenness of significant content, of a preoccupation with mere logistics which removes philosophy completely from men's business and bosoms. If the positivist accuses the existentialist of perpetrating “nonsense” in a technical sense, the latter retorts by accusing the positivist of reducing philosophy to nonsense in a pragmatic sense. (shrink)

In this paper I argue that it is inappropriate for us to blame others if it is not reasonable for us to believe that they are morally responsible for their actions. The argument for this claim relies on two controversial claims: first, that assertion is governed by the epistemic norm of reasonable belief, and second, that the epistemic norm of implicatures is relevantly similar to the norm of assertion. I defend these claims, and I conclude by briefly suggesting how this (...) putative norm of blame can serve as the basis for general norms of interpersonal generosity. (shrink)

In this entry we provide a critical review of recent work on the nature and ethics of blame, including issues of moral standing.