Uncoupling proteins (UCPs) regulate mitochondrial function, and thus cellular metabolism. Angiotensin‐converting enzyme (ACE) is the central component of endocrine and local tissue renin–angiotensin systems (RAS), which also regulate diverse aspects of whole‐body metabolism and mitochondrial function (partly through altering mitochondrial UCP expression). We show that ACE expression also appears to be regulated by mitochondrial UCPs. In genetic analysis of two unrelated populations (healthy young UK men and Scandinavian diabetic patients) serum ACE (sACE) activity was significantly higher amongst UCP3‐55C (rather than (...) T) and UCP2 I (rather than D) allele carriers. RNA interference against UCP2 in human umbilical vein endothelial cells reduced UCP2 mRNA sixfold (P < 0·01) whilst increasing ACE expression within a physiological range (<1·8‐fold at 48 h; P < 0·01). Our findings suggest novel hypotheses. Firstly, cellular feedback regulation may occur between UCPs and ACE. Secondly, cellular UCP regulation of sACE suggests a novel means of crosstalk between (and mutual regulation of) cellular and endocrine metabolism. This might partly explain the reduced risk of developing diabetes and metabolic syndrome with RAS antagonists and offer insight into the origins of cardiovascular disease in which UCPs and ACE both play a role. (shrink)

We explore the extent to which Anderson's (1987) theory of knowledge compilation can account for the relationship between instructions and practice in learning to use a simple device. Bibby and Payne (1993) reported experimental support for knowledge compilation in this domain. This article replicates the finding of a performance cross‐over between instruction type and task type that disappears with practice on the tasks. The research is extended by using verbal protocols to model the strategies of novice and more experienced (...) individuals. Production system models of these strategies suggest that knowledge compilation only provides an adequate account of practice for one of two Instruction groups. To model the strategy shifts for the second group, we employ a “procedure modification heuristic” (after Neches, 1987), which relies on access to a declarative model of the configuration of the device. This suggests that instructionally derived declarative knowledge may have a subtle ongoing effect on the changes in procedural knowledge with practice. (shrink)

Basic to all motile life is a differential approach/avoid response to perceived features of environment. The stages of response are initial reflexive noticing and orienting to the stimulus, preparation, and execution of response. Preparation involves a coordination of many aspects of the organism: muscle tone, posture, breathing, autonomic functions, motivational/emotional state, attentional orientation and expectations. The organism organizes itself in relation to the challenge. We propose to call this the “preparatory set” (PS). We suggest that the concept of the PS (...) can offer a more nuanced and flexible perspective on the stress response than do current theories. We also hypothesize that the mechanisms of bodymind therapeutic and educational systems (BTES) can be understood through the PS framework. We suggest that the BTES, including meditative movement, meditation, somatic education, and the body-oriented psychotherapies, are approaches that use interventions on the PS to remedy stress and trauma. We discuss how the PS can be adaptive or maladaptive, how BTES interventions may restore adaptive PS, and how these concepts offer a broader and more flexible view of the phenomena of stress and trauma. We offer supportive evidence for our hypotheses, and suggest directions for future research. We believe that the PS framework will point to ways of improving the management of stress and trauma, and that it will suggest directions of research into the mechanisms of action of BTES. (shrink)

This paper explores the role of regulation and legislation on influencing the development and diffusion of technologies and methods of crop production. To do this, the change in pesticide registration under European Regulation 1107/2009 ‘Placing Plant Protection Products on the Market’ was followed through the UK’s agricultural system of innovation. Fieldwork included: a series of interviews conducted with scientists, agronomists and industry organisations; a programme of visiting agricultural events; as well as sending an electronic survey to British potato growers. The (...) innovation system is noted to have made the legislation less restrictive than originally proposed. The most notable system response to the legislation is the adjustment of agrochemical company pesticide discovery strategy and their expansion into biologically derived treatments. There have also been other innovation responses: agricultural seed companies have been breeding in pathogen resistance in their cultivars; agricultural consultancies are prepared to recommend pathogen-resistant seeds; scientists are using the change as justification for adopting their solutions; the agricultural levy boards funded research into off-label pesticide uses; and producers, potato growers in particular, have been seeking advice, but not changing their growing practices. (shrink)

In this issue of the Hastings Center Report, Joshua Rager and Peter Schwartz reframe the justification for the use of opioid treatment agreements. Instead of documents used to define the roles and responsibilities of doctors and patients to one another in the course of opioid treatment for chronic pain and to describe the risks and benefits of therapy for the individual, OTAs are now proposed for use as “surveillance and monitoring” instruments. As such, they are specifically meant to disclose (...) the risks of opioid therapy and to describe the other processes and tools used to monitor abuse and diversion of medications. Given the crisis of the opioid overdose and death epidemic, along with this repurposing of OTAs as disclosure documents primarily, Rager and Schwartz argue that patient consent is not needed and that OTAs should be universally applied in clinical practices. We can all agree on the big picture goal of limiting the number of opioid prescriptions in order to minimize the tragedy of opioid overdose deaths. We disagree, though, about the acceptable level of collateral damage to people in pain who fall victim to fighting the war against the so-called opioid epidemic. (shrink)

Signs – Sounds – Semantics: Nature and Transformation of Writing Systems in the Ancient Near East. Edited by Gösta Gabriel, Karenleigh Overmann, and Annick Payne. Wiener Offene Orientalistik, vol. 13. Münster: Ugarit-Verlag, 2021. Pp. vi + 230, illus. €97.

Machine generated contents note: Preface; Introduction; Part I. Global Health, Definitions and Descriptions: 1. What is global health? Solly Benatar and Ross Upshur; 2. The state of global health in a radically unequal world: patterns and prospects Ron Labonte and Ted Schrecker; 3. Addressing the societal determinants of health: the key global health ethics imperative of our times Anne-Emmanuelle Birn; 4. Gender and global health: inequality and differences Lesley Doyal and Sarah Payne; 5. Heath systems and health Martin McKee; (...) Part II. Global Health Ethics, Responsibilities and Justice: Some Central Issues: 6. Is there a need for global health ethics? For and against David Hunter and Angus Dawson; 7. Justice, infectious disease and globalisation Michael Selgelid; 8. International health inequalities and global justice: toward a middle ground Norman Daniels; 9. The human right to health Jonathan Wolff; 10. Responsibility for global health? Allen Buchanan and Matt DeCamp; 11. Global health ethics: the rationale for mutual caring Solly Benatar, Abdallah Daar and Peter Singer; Part III. Analyzing Some Reasons for Poor Health: 12. Trade and health: the ethics of global rights, regulation and redistribution Meri Koivusalo; 13. Debt, structural adjustment and health Jeff Rudin and David Sanders; 14. The international arms trade and global health Salahaddin Mahmudi-Azer; 15. Allocating resources in humanitarian medicine Samia Hurst, Nathalie Mezger and Alex Mauron; 16. International aid and global health Anthony Zwi; 17. Climate change and health: risks and inequities Sharon Friel, Colin Butler and Anthony McMichael; 18. Animals, the environment and global health David Benatar; 19. The global crisis and global health Stephen Gill and Isabella Bakker; Part IV. Shaping the Future: 20. Health impact fund: how to make new medicines accessible to all Thomas Pogge; 21. Biotechnology and global health Hassan Masun, Justin Chakma and Abdallah Daar; 22. Food security and global health Lynn McIntyre and Krista Rondeau; 23. International taxation Gillian Brock; 24. Global health research: changing the agenda Tikki Pang; 25. Justice and research in developing countries Alex John London; 26. Values in global health governance Kearsley Stewart, Gerald T. Keusch and Arthur Kleinman; 27. Poverty, distance and two dimensions of ethics Jonathan Glover; 28. Teaching global health ethics James Dwyer; 29. Towards a new common sense: the need for new paradigms of global health Isabella Bakker and Stephen Gill; Index. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Schopenhauer's Pessimism and the Unconditioned Good MARK MIGOTTI SCHOPENHAUERTOOK PESSIMISMtO be a profound doctrine that had long been accepted by the majority of humanity, albeit usually in the allegorical form given to it by one or another religious creed. Accordingly, he credited himself, not with the discovery of pessimism, but with the provision of a satisfactory philosophical exposition and defense of its claims. It was, he contended, only within (...) the context of his philosophy, animated by the "single thought" that "the world is the self-knowledge of the will,"' that the ultimate significance of pessimism and the arguments demonstrating its inescapability can be brought to light. If, nevertheless, he sometimes appears to protest too much, to defend pessimism as if it were a striking and novel affair, he would have attributed this to the fact that he was, unfortunately, writing in the midst of one of the most naively optimistic cultures known to world history. 2 The philosophical reception of Schopenhauer's pessimism since the publication of The World as Will and Representation in 1818 would, one suspects, have been taken by him as further evidence of modern Western philosophy's optimistic somnambulance. For while other, comparably fundamental aspects of his thought--for example, his theories of action, of the self, and his criticisms of Kant--have received a welcome amount of fruitful, critical attention, his I would like to thank John Atwell, David Schmidtz, Susan Haack, Rudolf Makkreel and, especially,two anonymous referees, for prompting me to make substantial improvements to an earlier draft of this paper. ' Arthur Schopenhauer, Der handschrifllicher Nachlass 1, ed. Arthur Hiibscher (Frankfurt-amMain : Kramer, 1967),462; Manuscript Remains 1, trans. E. F.J. Payne(NewYork: Berg Publishing, 1988), 512. 'See, for example, Arthur Schopenhauer, D/e Welt als Wille und VorsteUung II. In Arthur Schopenhauer. Ziircher Ausgabe, ed. Arthur Hiibscher et. al. (Zurich: DiogenesVerlag, 1977),w 4:721, 732-33; The World as Will and Representation II, trans. E. F. J. Payne(New York: Dover Press, 1969),615, 625-26. Future references to this work willbe made within the text, by the abbreviation WW followed by section number, German edition volume and page number and English translation page number. [643] 644 JOURNAL OF THE HISTORY OF PHILOSOPHY 33:4 OCTOBER ~995 pessimism has not. Amongst enthusiastic followers it has sometimes been swallowed more or less whole, but from more independent-minded readers it has generally met with disdainful mockery or well-intentioned neglect.3 The aim of this paper is to help rectify' this imbalance. In the first of its four sections, I present an account of Schopenhauerian pessimism that can claim a good measure of textual support, and the essential features of which are found often enough in the secondary literature to warrant calling it the mainstream interpretation.4 In section 2 I show that, as critics have charged, the arguments for pessimism on this interpretation suffer from a pair of fatal ambiguities, and in section 3 I sketch an alternative argument for pessimism, one not so obviously open to the sort of knock-down refutation to which the first argument succumbs. In the paper's final section l explore further the philosophical consequences of this alternative argument for pessimism. 3Gyorg'yLukacs, "Schopenhauer," chapter ~,section 4 of The Destruction of Reason, trans. Peter Palmer (London: Merlin Press, 1979), 19~-243, isthe locusclassicusof an attitude of superior scorn. Bryan Magee, The Philosophy of Schopenhauer (Oxford: "the Clarendon Press, 1983), z3-14, D. W. Hamlyn, Schopentmuer (London: Routledge, z98o), *43, Michael Fox, "Schopenhauer on Death, Suicide, and Renunciation." in Schopenhauer: His Philosophical Achievement, ed. Michael Fox (Totowa, NJ: Barnes and Noble Books, 198o), ]47-7o, and David Cartwrigh*, "Schopenhauer on Suffering, Death, Guilt, and the Consolation of Metaphysics,"in Schopenhauer: New Essays in Hotwr ofHis 2ooth Birthday, ed. Eric yon der Luft (Lewiston,NY: Edwin Mellen Press, t988), 66, all incline to the viewthat it was temperament, not argument, that drove Schopenhauer to pessimism, while Patrick Gardiner, Schopenhatwr (London: Penguin Books, ]963), does not discuss pessimism by name. Not even Nietzsche, the deepest and most astute of Schopenhauer'scritics,can resistbarbs of the following sort: "Schopenhauer, although a pessimist, in ]act played the flute... (shrink)

How do we go about weighing evidence, testing hypotheses, and making inferences? According to the model of _Inference to the Best Explanation_, we work out what to infer from the evidence by thinking about what would actually explain that evidence, and we take the ability of a hypothesis to explain the evidence as a sign that the hypothesis is correct. In _Inference to the Best Explanation_, Peter Lipton gives this important and influential idea the development and assessment it deserves. (...) The second edition has been substantially enlarged and reworked, with a new chapter on the relationship between explanation and Bayesianism, and an extension and defence of the account of contrastive explanation. It also includes an expanded defence of the claims that our inferences really are guided by diverse explanatory considerations, and that this pattern of inference can take us towards the truth. This edition of _Inference to the Best Explanation_ has also been updated throughout and includes a new bibliography. (shrink)

"How do we go about weighing evidence, testing hypotheses and making inferences? According to the model of 'inference to the Best explanation', we work out what to inter from the evidence by thinking about what would actually explain that evidence, and we take the ability of a hypothesis to explain the evidence as a sign that the hypothesis is correct. In inference to the Best Explanation, Peter Lipton gives this important and influential idea the development and assessment it deserves." (...) "The second edition has been substantially enlarged and reworked, with a new chapter on the relationship between explanation and Bayesianism, and an extension and defence of the account of contractive explanation. It also includes an expanded defence of the claims that our inferences really are guided by diverse explanatory considerations, and that this pattern of inference can take us towards the truth. This edition of Inference to the Best Explanation has also been updated throughout and incudes a new bibliography."--BOOK JACKET. (shrink)

The relationship of part to whole is one of the most fundamental there is; this is the first and only full-length study of this concept. This book shows that mereology, the formal theory of part and whole, is essential to ontology. Peter Simons surveys and criticizes previous theories, especially the standard extensional view, and proposes a more adequate account which encompasses both temporal and modal considerations in detail. 'Parts could easily be the standard book on mereology for the next (...) twenty or thirty years.' Timothy Williamson, Grazer Philosophische Studien. (shrink)

The purpose of this article is to develop a conception of death with dignity and to examine whether it is vulnerable to the sort of criticisms that have been made of other conceptions. In this conception “death” is taken to apply to the process of dying; “dignity” is taken to be something that attaches to people because of their personal qualities. In particular, someone lives with dignity if they live well (in accordance with reason, as Aristotle would see it). It (...) follows that health care professionals cannot confer on patients either dignity or death with dignity. They can, however, attempt to ensure that the patient dies without indignity. Indignities are affronts to human dignity, and include such things as serious pain and the exclusion of patients from involvement in decisions about their lives and deaths. This fairly modest conception of death with dignity avoids the traps of being overly subjective or of viewing the sick and helpless as “undignified”. (shrink)

[1] The rise of modern paganism.--v. 2. The science of freedom.

The historian Ibn Khaldūn (d. 1406) is most often treated by historians of philosophy as part of the story of political philosophy in the Islamic world. While this is perfectly legitimate, it may be misleading when it comes to the question of the method he proposes for the historian. This paper argues that that method is in fact based on a different branch of (Aristotelian) science: natural philosophy. After rendering this proposition initially plausible by noting frequent references to "nature" in (...) the _Muqaddima_, the paper discusses a number of parallels between natural philosophy and history as Ibn Khaldūn conceives it. Ultimately it is suggested that this method is legitimated insofar as history is for Ibn Khaldūn a study of human nature. (shrink)

Peter Carruthers's essays on consciousness and related issues have had a substantial impact on the field, and many of his best are now collected here in revised form. The first half of the volume is devoted to developing, elaborating, and defending against competitors one particular sort of reductive explanation of phenomenal consciousness, which Carruthers now refers to as 'dual-content theory'. Phenomenal consciousness - the feel of experience - is supposed to constitute the 'hard problem' for a scientific world view, (...) and many have claimed that it is an irredeemable mystery. But Carruthers here claims to have explained it. He argues that phenomenally conscious states are ones that possess both an 'analog' intentional content and a corresponding higher-order analog content, representing the first-order content of the experience. It is the higher-order analog content that enables our phenomenally conscious experiences to present themselves to us, and that constitutes their distinctive subjective aspect, or feel.The next two chapters explore some of the differences between conscious experience and conscious thought, and argue for the plausibility of some kind of eliminativism about conscious thinking. Then the final four chapters focus on the minds of non-human animals. Carruthers argues that even if the experiences of animals aren't phenomenally conscious, this needn't prevent the frustrations and sufferings of animals from being appropriate objects of sympathy and concern. Nor need it mean that there is any sort of radical 'Cartesian divide' between our minds and theirs of deep significance for comparative psychology. In the final chapter, he argues provocatively that even insects have minds that include a belief/desire/perception psychology much like our own. So mindedness and phenomenal consciousness couldn't be further apart.Carruthers's writing throughout is distinctively clear and direct. The collection will be of great interest to anyone working in philosophy of mind or cognitive science. (shrink)

By the time of his death in 2006, Sir Peter Strawson was regarded as one of the world's most distinguished philosophers. First published thirty years ago but long since unavailable, _Freedom and Resentment_ collects some of Strawson's most important work and is an ideal introduction to his thinking on such topics as the philosophy of language, metaphysics, epistemology and aesthetics. Beginning with the title essay _Freedom and Resentment_, this invaluable collection is testament to the astonishing range of Strawson's thought (...) as he discusses free will, ethics and morality, logic, the mind-body problem and aesthetics. The book is perhaps best-known for its three interrelated chapters on perception and the imagination, subjects now at the very forefront of philosophical research. This reissue includes a substantial new foreword by Paul Snowdon and a fascinating intellectual autobiography by Strawson. (shrink)

This study presents a substantial and often radical reinterpretation of some of the central themes of Locke's thought. Professor Alexander concentrates on the Essay Concerning Human Understanding and aims to restore that to its proper historical context. In Part I he gives a clear exposition of some of the scientific theories of Robert Boyle, which, he argues, heavily influenced Locke in employing similar concepts and terminology. Against this background, he goes on in Part II to provide an account of Locke's (...) views on the external world and our knowledge of it. He shows those views to be more consistent and plausible than is generally allowed, demonstrating how they make sense and enable scientific explanations of nature. In examining the views of Locke and Boyle together, the book throws light both on the development of philosophy and the beginnings of modern science, and in particular it makes a considerable and original contribution to our understanding of Locke's philosophy. (shrink)

Journal Name: Philologus Issue: Ahead of print.

sirThe recent article by Evans in the journal on the single blind placebo in drug research is timely and its conclusions were persuasive. The basic premiss that single blind placebo “washout” periods are ethically specious was well argued and I agree that from a scientific point of view they have no valid justification. The real reasons ….

The essays in this volume address three fundamental questions in the philosophy of science: What is required for some fact to be evidence for a scientific ...

The question of toleration matters more than ever. The politics of the twenty-first century is replete with both the successes and, all too often, the failures of toleration. Yet a growing number of thinkers and practitioners have argued against toleration. Some believe that liberal democracies are better served by different principles, such as respect of, or recognition for, people's ways of life. Others argue that because the liberal state should be entirely neutral or indifferent towards people's ways of life, it (...) can no longer be tolerant - it has no grounds on which it can object, and so there is nothing left to tolerate.Respecting Toleration provides a new, original, and provocative take on the question of toleration and its application to the politics of contemporary diversity. The volume demonstrates how toleration - despite its critics - is essential to any liberal political order. Peter Balint argues that from a conceptual viewpoint, toleration is entirely compatible with liberal politics; and from a normative viewpoint, it is utterly essential. The volume argues that if one cares about people living divergent lives, then it is liberal toleration that should be respected by legislators and policy makers, and not people's differences. It is a book that will shape the debate and demand a response from all who are interested in which political structures most fairly accommodate the competing ways of life that characterise contemporary diversity.Key Features:Develops a new framework of political tolerationProvides a clear demonstration and analysis of complex concepts and argumentsProvides extensive practical and theoretical examples. (shrink)

By the time of his death in 2006, Sir Peter Strawson was regarded as one of the world's most distinguished philosophers. First published thirty years ago but long since unavailable, _Freedom and Resentment_ collects some of Strawson's most important work and is an ideal introduction to his thinking on such topics as the philosophy of language, metaphysics, epistemology and aesthetics. Beginning with the title essay _Freedom and Resentment_, this invaluable collection is testament to the astonishing range of Strawson's thought (...) as he discusses free will, ethics and morality, logic, the mind-body problem and aesthetics. The book is perhaps best-known for its three interrelated chapters on perception and the imagination, subjects now at the very forefront of philosophical research. This reissue includes a substantial new foreword by Paul Snowdon and a fascinating intellectual autobiography by Strawson. (shrink)

[Peter Lipton] From a reliabilist point of view, our inferential practices make us into instruments for determining the truth value of hypotheses where, like all instruments, reliability is a central virtue. I apply this perspective to second-order inductions, the inductive assessments of inductive practices. Such assessments are extremely common, for example whenever we test the reliability of our instruments or our informants. Nevertheless, the inductive assessment of induction has had a bad name ever since David Hume maintained that any (...) attempt to justify induction by means of an inductive argument must beg the question. I will consider how the inductive justification of induction fares from the reliabilist point of view. I will also consider two other well-known arguments that can be construed as inductive assessments of induction. One is the miracle argument, according to which the truth of scientific theories should be inferred as the best explanation of their predictive success; the other is the disaster argument, according to which we should infer that all present and future theories are false on the grounds that all past theories have been found to be false. \\\ [John Worrall] Science seems in some ways to have been remarkably successful. What does this success tell us about the epistemological status of current scientific claims? Peter Lipton considers various meta-inductive arguments each of which start from premises about science's 'track record'. I show that his endorsements of the 'strongest' of these are, on analysis, remarkably weak. I argue that this is a reflection of difficulties within the general epistemological framework that he adopts-that of reliabilism. Finally, I briefly outline the quite different approach that I take to this issue, in the process responding to Lipton's criticisms of the 'pessimistic meta-induction'. (shrink)

[Peter Simons] Commonsense ontology contains both continuants and occurrents, but are continuants necessary? I argue that they are neither occurrents nor easily replaceable by them. The worst problem for continuants is the question in virtue of what a given continuant exists at a given time. For such truthmakers we must have recourse to occurrents, those vital to the continuant at that time. Continuants are, like abstract objects, invariants under equivalences over occurrents. But they are not abstract, and their being (...) invariants enables us to infer both their lack of temporal parts and that non-invariant predications about them must be relativized to times. \\\ [Joseph Melia] In this paper I try to eliminate occurrents from our ontology. I argue against Simons' position that occurrents are needed to supply truthmakers for existential claims about continuants. Nevertheless, those who would eliminate occurrents still need some account of our willingness to assert sentences that logically entail their existence. Though it turns out to be impossible to paraphrase away our reference to occurrents, I show that the truthmakers for such sentences are facts that involve only continuants. This is enough to allow us to regard our ordinary talk about occurrents as fictional. Finally, I argue that a proper conception of the underlying temporal facts about continuants can both avoid the problematic tensed theory of time and the problem of temporary intrinsics. (shrink)