Sterols and the reductant nicotinamide adenine dinucleotide phosphate (NADPH), essential for eukaryotic life, arose because of, and as an adaptation to, rising levels of molecular oxygen (O2). Hence, the NADPH and O2‐intensive process of sterol biosynthesis is inextricably linked to redox status. In mammals, cholesterol biosynthesis is exquisitely regulated post‐translationally by multiple E3 ubiquitin ligases, with membrane associated Really Interesting New Gene (RING) C3HC4 finger 6 (MARCHF6) degrading at least six enzymes in the pathway. Intriguingly, all these MARCHF6‐dependent enzymes require (...) NADPH. Moreover, MARCHF6 is activated by NADPH, although what this means for control of cholesterol synthesis is unclear. Indeed, this presents a paradox for how NADPH regulates this vital pathway, since NADPH is a cofactor in cholesterol biosynthesis and yet, low levels of NADPH should spare cholesterol biosynthesis enzymes targeted by MARCHF6 by reducing its activity. We speculate MARCHF6 helps mammalian cells adapt to oxidative stress (signified by low NADPH levels) by reducing degradation of cholesterogenic enzymes, thereby maintaining synthesis of protective cholesterol. (shrink)

This commentary is a call to action for researchers to create and use genome-wide association studies (GWASs) with previously missed age groups (e.g., infancy, elderly), which will improve our ability to ask important developmental questions using genetic data to trace pathways across the lifespan.

This book's importance is derived from three sources: careful conceptualization of teacher induction from historical, methodological, and international perspectives; systematic reviews of research literature relevant to various aspects of teacher induction including its social, cultural, and political contexts, program components and forms, and the range of its effects; substantial empirical studies on the important issues of teacher induction with different kinds of methodologies that exemplify future directions and approaches to the research in teacher induction.

The ability to feel pain is a property of human beings that seems to be based entirely in our biological natures and to place us squarely within the animal kingdom. Yet the experience of pain is often used as an example of a mental attribute with qualitative properties that defeat attempts to identify mental events with physiological mechanisms. I will argue that neurophysiology and psychology help to explain the interwoven biological and subjective features of pain and recommend a view of (...) pain which differs in important respects from the one most commonly accepted. (shrink)

pain' and ┌I think that p┐ express the pain and the thought that p, themselves. The book is most impressive. It is packed with careful argument, and addresses a remarkable range of important issues about the mind. I have very much enjoyed studying it.

In this last of our selection of papers from the London Medical Group Conference on Pain, Gilbert Lewis, through his experiences of living in New Guinea describes to us the various rites, rituals and uses of pain in societies other than our own. He outlines, by example, how what often seems the natural behaviour to us for helping a sufferer in fact, can make matters far worse for other peoples. Although different societies approach the problem of pain from many routes (...) the aim of all is to relieve pain for the sufferers. If the sufferer says he feels relief then that is surely what counts. (shrink)

Fetal pain has long been a contentious issue, in large part because fetal pain is often cited as a reason to restrict access to termination of pregnancy or abortion. We have divergent views regarding the morality of abortion, but have come together to address the evidence for fetal pain. Most reports on the possibility of fetal pain have focused on developmental neuroscience. Reports often suggest that the cortex and intact thalamocortical tracts are necessary for pain experience. Given that the cortex (...) only becomes functional and the tracts only develop after 24 weeks, many reports rule out fetal pain until the final trimester. Here, more recent evidence calling into question the necessity of the cortex for pain and demonstrating functional thalamic connectivity into the subplate is used to argue that the neuroscience cannot definitively rule out fetal pain before 24 weeks. We consider the possibility that the mere experience of pain, without the capacity for self reflection, is morally significant. We believe that fetal pain does not have to be equivalent to a mature adult human experience to matter morally, and so fetal pain might be considered as part of a humane approach to abortion. (shrink)

This chapter aims to illuminate ways in which hope was significant in the philosophy of classical Greece. Although ancient Greek philosophies contain few dedicated and systematic expositions on the nature of hope, they nevertheless include important remarks relating hope to the good life, to reason and deliberation, and to psychological phenomena such as memory, imagination, fear, motivation, and pleasure. After an introductory discussion of Hesiod and Heraclitus, the chapter focuses on Plato and Aristotle. Consideration is given both to Plato’s direct (...) comments on hope and to the narrative contexts of his dialogues, with analysis of Plato’s positive and negative representations of hope, hope’s relationship to reason, and Plato’s more psychological approach in the Philebus, where hope finds a place among memory, recollection, pleasure, and pain. The chapter then reviews Aristotle’s discussions of confidence, hope, and courage, observing that although Aristotle does not mention hope as a virtue, he does note its importance to human agency and deliberation and as a foundation for the further development of virtue. The chapter concludes that discussions surrounding hope in ancient Greek philosophy are rich and challenging and can serve as a lively stimulus to further exploration of the concept of hope. (shrink)

Excerpt from Genetic Philosophy of Education: An Epitome of the Published Educational Writings, of President G Stanley Hall, of Clark University All must admit that there is a lack at the present time, at least among the rank and file of teachers, and in the public mind generally, of any adequate philoso phy of education, or even Of a point of view from which the themes of school and home can be dis cussed broadly and intelligently. The older philoso phies (...) of F roebel, Hegel, and Herbart are certainly in sufficient to meet present needs, and especially in the training of teachers is this painfully felt. They are not only obscure, and little inspiring, either Of breadth of thought or intelligent practice but they fail en tirely to connect with the teacher 3 daily life, unless they be taught in a very shallow and formal way. 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)

This paper argues that McDowell wrongly assumes that “terror”, Cavell’s reaction to the radical contingency of our shared modes of knowing or our “attunement”, expresses a skepticism that is antinomically bound to an equally unacceptable dogmatism because Cavell rather regards terror as a mood that reveals the “truth of skepticism”, namely, that there is no conclusive evidence for necessary attunement on pain of a category error, and that a precedent for McDowell’s misunderstanding is Hegel’s argument for necessary attunement in a (...) system of knowing, whose refutation Schelling holds it is the “merit of skepticism” to provide. (shrink)

A puzzle arises when we consider that, for Kant, the categories are 'original acquisitions' of our understanding to which we must nevertheless prove our entitlement via 'deduction', on pain of dogmatism. I resolve this puzzle by articulating skepticism’s role in the transcendental deduction, drawing on Kant’s construal of the skeptical 'question quid juris' in the juridical terms of entitlement to property. I then situate skepticism’s transformative potential within what Kant regards as reason’s 'maturation' from dogmatism toward self-knowledge. Finally, I contrast (...) Hegel’s account of spirit’s progress toward 'absolute knowledge', which shifts both the mode of skepticism and the prospect of maturation. (shrink)

At W.D. 202–12 Hesiod relates his ανος for the edification of the recalcitrant βασιλες, who must themselves admit the truth of the fable's moral . A hawk has seized a nightingale, and crushes her cries of misery by saying that she is in the claws of one who is πολλν ρείων and who is therefore at liberty to dispense with her as he pleases: anyone who tries to resist κρείσσονες is mad, for he has no chance of winning and merely (...) adds physical pain to the shame of defeat. Just what were the βασιλες to have made of this? Hesiod's most recent editor claims that ‘Hesiod does not manage to make it [the ανος] into a lesson for them [the kings]’, and ‘can only proceed by saying “Well, don't you behave like that” ’. (shrink)

Medical decisions regarding end-of-life care have undergone significant changes in recent decades, driven by changes in both medicine and society. Catholic tradition in medical ethics offers clear guidance in many issues, and a moral framework accessible to those who do not share the same faith as well as to members of its faith community. In some areas, a Catholic perspective can be seen clearly and confidently, such as in teachings on the permissibility of suicide and euthanasia. In others, such as (...) withdrawal of nutrition and hydration, the Church does not yet speak with one voice and has not closed out the discussion. Yet, it is not in the teaching on individual issues that a Catholic moral tradition offers the most help and comfort, but in its account of what it means to lead a life in Christ, and to prepare for a Christian death. As in the problem of pain and suffering, it is the spiritual support more than the ethical guidance that helps both patients and physicians bear the unbearable and fathom the unfathomable. (shrink)

Materialism in the philosophy of mind — materialismPM — is the view that everything mental is material (or, equivalently, physical). Consciousness — pain, emotional feeling, sensory experience, and so on — certainly exists. So materialismPM is the view that consciousness is wholly material. It has, historically, nothing to do with denial of the existence of consciousness. Its heart is precisely the claim that consciousness — consciousness! — is wholly material. [2] ‘Physicalism’, the view introduced by members of the Vienna Circle (...) in the late 1920s, also has nothing to do with denial of the existence of consciousness. [3] Recently the words ‘materialism’ and ‘physicalism’ have come to be treated as synonymous, and as names for a position in the philosophy of mind that does involve denial of the existence of consciousness. They’ve been used to name a position that (i) directly rejects the heart of materialism (materialismPM) and (ii) is certainly false. This is a pity, because they’re good terms for a view that is very likely true. (shrink)

Mr. Galanas, an eighty‐six‐year‐old man, intentionally shot himself in the chest and abdomen. Surprisingly, the bullet damaged only his distal pancreas and part of his colon, requiring a diverting colostomy to prevent leakage of bowel fluids into his abdomen. After being admitted, he lies intubated in the intensive care unit awaiting surgery to repair his colon. He is responsive but does not demonstrate clear decision‐making capacity. He grudgingly accepts pain medications but refuses antibiotics and antidepressants. He has a living will (...) that gives his wife durable power of attorney and also explicitly states a desire to refuse all medical interventions if he is permanently unconscious or in an end‐stage condition. Mrs. Galanas reports frequent conversations in which her husband said he would not want to be sustained on life support. She also says that he often mentioned he would not want an ostomy bag—a likely, albeit temporary, outcome of the proposed surgery.His physicians are nervous about withholding medical interventions when Mr. Galanas's injury is the result of a suicide attempt and his prognosis is good. Should the care team surgically repair his injured colon, regardless of the patient's capacity, his advance directive, and his wife's statement that he would not want surgery or other life‐sustaining treatment? (shrink)

The question of whether a fetus can experience pain is an immense challenge. The issue demands consideration of the physical and psychological basis of being and the relation between the two. At the center of this debate is the question of how it is that we are conscious, a question that has inspired the writing of some of our most brilliant contemporary philosophers and scientists, with one commentary suggesting surrender. In my earlier review I attempted to draw together the various (...) strands of thinking that had attacked the question of fetal pain and relate them back to the bigger question of consciousness. In their vituperative response, Benatar and Benatar bite off my finger before looking to where I am pointing. I will examine each of their criticisms and attempt to redirect the readers' interest towards examining the subjectivity of pain and the mediating links between physiology and experience. (shrink)

Keown’s critique of the Marty report is as flawed as the report it criticisesIn 2003, a report by the Council of Europe’s social, health and family affairs committee appeared, questioning the council’s opposition to the legislation of euthanasia. This report is known as the Marty report. The report contains several arguments in favour of legalisation of euthanasia. The first argument focuses on the gap between practice and law. Legalisation would bring existing practices of euthanasia out of the grey area, and (...) make them more open to control. The second argument is that as long as euthanasia is legally forbidden, patients are forced to continue living in unbearable pain and suffering. In his critique of the Marty report, John Keown concludes that both arguments are invalid.1 He questions the presumed gap between practice and law, and criticises the conclusion that such a gap would imply that the law should be changed. He also argues that the notion of unbearable pain and suffering is highly problematic, and cannot serve as a justification for euthanasia. Although Keown’s discussion shows thorough knowledge of the issue at hand, his conclusions are one sided and his dismissal of the position taken in the Marty report is too easy. In order to substantiate this, I will go into Keown’s critique of the two arguments in the report.THE GAP BETWEEN PRACTICE AND LAWAccording to the Marty report, legalisation of euthanasia would bring existing practice into the open, and make decisions less arbitrary. Keown questions this argument in two ways. Firstly, he raises doubt as to whether the existing laws forbidding euthanasia are that often broken in practice. Several studies indicate that euthanasia is not very common in medical practice. If this is the case, the gap between law and practice is not as large as one might think. Keown rightly... (shrink)

Do we remember what pain feels like? Investigations into this question have sometimes led to ambiguous or apparently contradictory results. Building on research on pain memory by Rohini Terry and colleagues, I argue that this lack of agreement may be due in part to the difficulty researchers face when trying to convey to their study's participants the type of memory they are being tasked with recalling. To address this difficulty, I introduce the concept of 'qualitative memory', which, arguably, is the (...) sort of memory we have of what red looks like yet lack with respect to pain. I also briefly address a number of consequences the acknowledgment of qualitative memory would potentially have for philosophy, arguing that if we fail to have qualitative memories of certain sensations, such as pain, the standard philosophical accounts of experience, rational choice, and the sources of moral action may all need revision. (shrink)

In Ian Brassington’s article in a previous issue of this journal, he argues that suicide for the purpose of avoiding suffering is not, as Kant has contended, contrary to the moral law. Brassington’s objections are not cogent because they rely upon the exegetically incorrect premise that according to Kant the priceless value of personhood is in the noumenal world that we have no perception of. On the basis of Kant’s normative, metaphysical and epistemological theory, I argue, contrary to Brassington, that (...) according to Kant personhood’s moral value is explicitly in the sensible, phenomenal realm. While I argue that suicide solely to avoid suffering is immoral, I show that Kant’s normative system allows some acts of suicide to be morally permissible. In the course of the discussion of the value of humanity’s rationality and the immorality of suicide, I will discuss the broader modern medical ethical implications of Kant’s arguments, such as the moral impermissibility of using rationality depriving drugs, such as ketamine, solely to avoid pain. (shrink)

In recent years, the opioid crisis in the United States has sparked significant discussion on doctor–patient interactions concerning chronic pain treatments, but little to no attention has been given to investigating the vocal aspects of patient talk. This exploratory sociolinguistic study intends to fill this knowledge gap by employing prosodic discourse analysis to examine context-specific linguistic features used by the interlocutors of two distinct medical interactions. We found that patients employed both low pitch and creak as linguistic resources when describing (...) chronic pain, narrating symptoms and requesting opioids. The situational use of both features informs us about the linguistic ways in which patients frame fraught issues like chronic pain in light of the current opioid crisis. This study expands the breadth of phonetic analysis within the domain of discourse analysis, serving to illuminate discussions surrounding the illocutionary role of the lower vocal tract in expressing emotions. (shrink)

In a long and important sentence in the Timaeus , Plato explains that, whereas that which truly or really is () cannot come to be in anything else, sensible things, being mere images, must necessarily come to be in something else, on pain of not existing at all.

Pain management has improved in the past few decades. Opioid analgesics have become the mainstay in the treatment of cancer pain whilst inter-disciplinary pain management programmes are the generally accepted approach to chronic pain of non-malignant origin. Recently some pain specialists have advocated the use of opioids in the long-term management of non-cancer pain. This has raised some fundamental questions about the purpose of pain management. Is it best to opt for maximum pain relief and comfort, or should one emphasise (...) function and activity as higher priorities? Will the use of opioids create more autonomy for pain sufferers or will this add handicaps to lives which are already limited? Until more clinical outcome data are available we advocate caution in the use of opioid analgesia. Such caution can, and does, raise questions about the rights of the patient and the rights of the prescriber in a context where the facts do not point to a clear course of action. (shrink)

This paper examines the question of whether a fetus can feel pain. The question is divided into four sub questions: What is pain? What is the neurology of pain processing? What is the fetus? Are there good reasons for holding that fetuses feel pain? Pain is suggested to be a multi‐dimensional phenomenon drawing on emotional and sensory processes – a consequence of a gradual development involving a number of noxious events rather than an automatic consequence of injury or disease. The (...) non‐automaticity of pain is emphasised in the discussion of pain neurology that defies explanations based on a specialised neuronal ‘pain‐centre’. The development of the fetus is considered with respect to developmental neurobiology, behavioural and neurological responses to stimulation, and hormonal and neurochemical responses to noxious stimulation. While acknowledging that the development of the fetus is complex, especially after 26 weeks gestation, considerable development is still to occur, even after birth. The fetal pain literature is criticised for tending to exaggerate fetal development. Finally, the difficulty of explaining the subjectivity of pain in materialist terms is discussed. Pain is suggested to arise with development of the necessary neurological, cognitive and emotional structures. Pain experience is placed at approximately 12 months of age, though this is within the context of a continuum of awareness rather than a straight ‘on‐off’ switch. The major moral implication of this stance is to place the burden of proof for analgesic use onto clinical measures, rather than relying upon the, so far, poorly supported assumption of pain awareness. (shrink)

The little-known story of the architectural project that lay at the heart of Paine's grand political vision for the United States. Thomas Jefferson praised Tom Paine as the greatest political writer of the age. The author of 'Common Sense' and Rights of Man, Paine helped make revolutions in America and France. But beyond his inspiring calls to action, Paine harbored a deeper political vision for his adopted country. It was embodied in an architectural project that he (...) spent decades planning: an iron bridge to span the Schuylkill River at Philadelphia. The bridge was Paine's answer to the political puzzle of the new nation: how to sustain a republic as large and geographically fragmented as the United States. Among its patrons were other giants of the time, including Benjamin Franklin and Edmund Burke, Paine's ideological opponent. Set against the background of the American Revolution, the story of his iron bridge reveals a new Tom Paine and connects this revolutionary to the vast program of internal improvements that soon transformed America"--Provided by publisher. (shrink)

In this piece I discuss two ways in which providers may become able to treat patients better. The first is for them to encourage all medical parties, including medical students, to always speak up. The second is to take initiatives to learn of pain that patients feel but neither show nor spontaneously report. They may refer to this pain as invisible pain, often bitterly, in that others not seeing their pain judge them wrongly and harshly. Providers, once seeing this pain, (...) are encouraged to then take additional measures to try to alleviate it. Clinical examples provided to illustrate the range of treatments providers may add are post-traumatic stress disorders, problems involving substance use, and hoarding disorders. Similar concerns regarding people who are deaf and hard of hearing are also addressed. (shrink)

In April 1939, G. E. Moore read a paper to the Cambridge University Moral Science Club entitled ‘Certainty’. In it, amongst other things, Moore made the claims that: the phrase ‘it is certain’ could be used with sense-experience-statements, such as ‘I have a pain’, to make statements such as ‘It is certain that I have a pain’; and that sense-experience-statements can be said to be certain in the same sense as some material-thing-statements can be — namely in the sense that (...) they can be safely counted on. When Moore later read his paper to Wittgenstein, Wittgenstein took violent exception to it, and the two entered into a heated exchange. The only known notes of this exchange are a previously unpublished verbatim record of part of it, taken by Norman Malcolm. This paper is an edition of Malcolm’s notes. These notes are valuable for both philosophical and scholarly reasons. They give us a glimpse of a sustained exchange between Wittgenstein and a real-life interlocutor; they contain a defence by Wittgenstein of the idea that a word’s use can illuminate its meaning; and they provide evidence of Wittgenstein’s philosophical engagement with the topic of certainty, and with Moore’s thought on it, long before he began to write the notes which make up On Certainty, in 1949. (shrink)

Pain alone does not settle the issue of vivisectionIn his paper, Lab animals and the art of empathy, David Thomas presents his case against animal experimentation. That case is a rather unusual one in certain respects. It turns upon the fact that, for Thomas, nothing can be proved or established in ethics, with the result that what we are left to operate with, apart from assumptions about cases that we might choose to make, are people’s feelings. We cannot show or (...) demonstrate that Pol Pot did anything morally wrong; we just have to hope, as seems not unreasonably demanding, that most people feel pretty strongly about large scale slaughter of human beings. Since nothing can be proven, we turn instead to our feelings and the three claims that Thomas features in his paper: that we should empathise with all creatures who can feel pain and suffer; that we should be consistent in condemning things based upon a similar degree of suffering involved and so treat like cases alike, and that we should take consent seriously, and, where the possibility of consent is absent, take seriously the notion of the best interests of the creature involved. Thomas concludes his paper with a succinct statement of his position: “In other words, we should look at things from the perspective of the victim, human or animal, not that of the would be exploiter. By this yardstick, animal experiments are as immoral as non-consensual experiments on people. In each case, the degree of immorality is in direct proportion to the degree of suffering caused—experiments causing severe suffering are more immoral than those causing only mild, transient suffering. Crucially, however, an experiment causing severe suffering to an animal is as immoral as one causing severe suffering to a person.”All animal experiments, therefore, have …. (shrink)