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.

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)

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.

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)

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)

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)

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 examines Bohdan Boichuk’s poetry by looking into the role his childhood memories played in forming his poetic imagination. Displaced by World War II, the poet displays a unique capacity to transcend his traumatic experiences by engaging in creative writing. Eyewitnessing war atrocities perpetrated by the Nazis does not destroy his belief in the healing power of poetry; on the contrary, it makes him appreciate poetry as the only existentially worthy enterprise. Invoking Gaston Bachelard’s classic work The Poetics of (...) Reveries: Childhood, Language, and the Cosmos, I argue that Boichuk’s vivid childhood memories, however painful they might be, helped him poetically recreate and reimagine fateful moments of his migrant life. (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)

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)

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)

Pain, suffering and positive emotions in patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious states (MCS) pose clinical and ethical challenges. Clinically, we evaluate behavioural responses after painful stimulation and also emotionally-contingent behaviours (e.g., smiling). Using stimuli with emotional valence, neuroimaging and electrophysiology technologies can detect subclinical remnants of preserved capacities for pain which might influence decisions about treatment limitation. To date, no data exist as to how healthcare providers think about end-of-life options (e.g., withdrawal of artificial nutrition (...) and hydration) in the presence or absence of pain in non-communicative patients. Here, we aimed to better clarify this issue by re-analyzing previously published data on pain perception (Prog Brain Res 2009 177, 329–38) and end-of-life decisions (J Neurol 2010 258, 1058–65) in patients with disorders of consciousness. In a sample of 2259 European healthcare professionals we found that, for VS/UWS more respondents agreed with treatment withdrawal when they considered that VS/UWS patients did not feel pain (77%) as compared to those who thought VS/UWS did feel pain (59%). This interaction was influenced by religiosity and professional background. For MCS, end-of-life attitudes were not influenced by opinions on pain perception. Within a contemporary ethical context we discuss (1) the evolving scientific understandings of pain perception and their relationship to existing clinical and ethical guidelines; (2) the discrepancies of attitudes within (and between) healthcare providers and their consequences for treatment approaches, and (3) the implicit but complex relationship between pain perception and attitudes toward life-sustaining treatments. (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)

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)

The idea that what is intrinsically good for people must be something they want or care about is a compelling one. Goal-fulfillment theories of well-being, which make this idea their central tenet, have a lot going for them. They offer a good explanation of why we tend to be motivated to pursue what’s good for us, and they seem to best explain how well-being is especially related to individual subjects. Yet such theories have been under attack recently for not being (...) able to account for robust or basic bads, such as pain and nausea. This paper argues that a psychologically informed goal-fulfillment theory can accommodate intuitions about robust bads by relying on aversions. Attending to aversion highlights a different sort of problem for goal-fulfillment theories, which comes from the possibility of a person who is so depressed that they have no goals or desires at all. We end the paper with a discussion of how empirically informed goal-fulfillment theories can account for the badness of the most serious form of depression. (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)

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)

Inadequate pain control, especially in older adults, remains a significant issue when caring for this population. Older adults, many of whom experience multiple acute and chronic conditions, are especially vulnerable to having their pain seriously underassessed and inadequately treated. Nurses have an ethical obligation to appropriately treat patients’ pain. To fulfill their ethical obligation to relieve pain in older patients, nurses often need to advocate on their behalf. This article provides an overview of the persistent problem of undertreated pain in (...) older adults and explores how nurses can meet this ethical duty through the application of Beauchamp and Childress’ three principles of beneficence. (shrink)

In this volume, G. Marian Kinget's classic work, On Being Human, can be read for the first time in light of a second, previously unpublished work, Pleasure And Pain. Taken together, these two works offer a new generation of readers a comprehensive picture of the insights, principles, and goals of humanistic psychology. On Being Human, Kinget's pioneering work, which arose from the original humanistic revolution in psychology, systematically describes the characteristics that make human beings different from all other forms of (...) life. In this work, Kinget explores man in his full nature not solely as a biological organism modified by experience and culture. She presents a person as a symbolic entity capable of pondering his existence, and lending it meaning and direction. Man is the only animal who knowingly exists in space and time, manifesting transcendental and metaphysical concern throughout history and culture. On Being Human presents the fundamentals of any valid approach to psychology as well as to other fields concerned with the individuality of the human being. It describes the specific human capacities for reflective thought and declarative language, and it discusses the unique ability of humans to devise culture and question origins. Pleasure and Pain considers the interdependence of human pleasure and pain. This idea, which leads to unnecessary fears and unwarranted expectations, goes unrecognized in a contemporary western society focused on the accumulation of pleasure without any awareness of the duality of the pleasure-pain experience. Kinget refutes the widespread fallacy that fun lies in the means, when it actually lies in the subject, and she discusses the human potential for autonomous "management" of the pleasure-pain dimension of human existence. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Pains And Gains Of Rural Health Practice:Lessons Books Never TaughtSridevi Seetharam, Bindu Balasubramaniam, G. S. Kumar, and M. R. SeetharamHow The Journey BeganIn the early 1980s, as fresh graduates from Mysore Medical College in southern India, we were brimming with a zeal to "cure the sick" and "change the world." We had an ideal of evidence-based, rational, ethical and equitable health care and set out to serve rural and (...) under-served communities which included displaced forest-based tribes. In the initial years, with the naivety of the inexperienced, we believed that by correcting the dehydration of the doe-eyed six-year-old Mare and giving her a free course of antibiotics, we had made health care accessible to her. Much to our dismay, within a month, Mare was back in the outpatient clinic, with diarrhea all over again and looking thinner than ever. We realized that it was a losing battle to keep her healthy as long as she continued to drink water from the same contaminated stream, live in unhygienic surroundings, and eat only the paltry meals that her family could barely afford. We gradually began to connect these living examples to what our preventive medicine text books had stressed all along—there are many social determinants of health which, if left unaddressed, do not permit realization of the vision of health for all.Such instances continually pulled us out of the hospital building and into the villages and tribal hamlets. We discovered that our textbook of Preventive and Social Medicine (Park, 1986) (P&SM as we used to call it), was our most valuable possession. [End Page 106] We devoured the descriptions of national health programs, sanitation procedures, water treatment protocols, and maintenance of cold chain for vaccines with a completely new perspective. We discovered the Manual of Basic Techniques for a Health Laboratory, (World Health Organization, 1980) detailing how to set up a laboratory with low cost, reliable and simple methods. We learned to drive a jeep to haul supplies and patients. To step up the level of clinical care, some of us pursued post-graduate programs and equipped ourselves to provide more specialized care too. It has been over two decades since we embarked on this journey. We have encountered a variety of perplexing dilemmas with no clear solutions. We have sometimes been compelled to adopt health practices that were not really evidence-based, seemingly irrational, inequitable and even downright unethical. This narration describes only a few of our thousands of cases, and hopefully conveys our periods of self-doubt, despair and hope, as well as, the challenges we face to reconcile with the difficult choices we are forced to make every day.Unforeseen Challenges in Saving Mothers and ChildrenHigh maternal and child mortality rates have been one of the most disturbing aspects of the health care scenario in rural India. To ensure immunization of all children, health workers with vaccine carriers go from village to village and hamlet to hamlet to reach those infants that would have missed visits to the immunization clinics. Our grass-root workers facilitate these visits by identifying households with such children. Occasionally, they encounter families who spirit away the infant into the adjoining woods as soon as the health worker is seen approaching, and blandly proclaim that the child is not at home. Despite reassurance and counseling about the safety and necessity of the vaccine, their apprehensions and misconceptions are insurmountable. What is the extent of the responsibility of the health worker? Is it ethical to hunt down the child and force the administration of the vaccine in view of the public health gains, besides the child's welfare?A few months ago, a pre-term neonate was admitted to our hospital, but worsened and needed referral to a higher centre in the city. The family refused to go despite repeated persuasion and detailed explanation about the technical limitations of care at our centre. From the family's perspective, the variety of social, cultural, and monetary challenges they would face in the city were themselves limitations for care. We were compelled to retain the baby and continue giving the best care we could.Two... (shrink)

Specialists and primary care physicians play an integral role in treating the twin epidemics of pain and addiction. But inadequate access to specialists causes much of the treatment burden to fall on primary physicians. This article chronicles the differences between treatment contexts for both pain and addiction — in the specialty and primary care contexts — and derives a series of reforms that would empower primary care physicians and better leverage specialists.

In lieu of an abstract, here is a brief excerpt of the content:Criminal Law, Pain Relief, and Physician Aid in DyingFaye Girsh, Ed.D., Executive DirectorMadam:The article by Cantor and Thomas on “Pain Relief, Acceleration of Death, and Criminal Law” (KIEJ, June 1996) was a tortured attempt to develop criteria for the humane and compassionate physician who tries to serve the needs of a patient in unremitting pain. There are three areas that merit comment.The authors dealt with pain medications that might (...) have the undesirable side effect of causing death. They did not mention tolerance, which usually occurs in a patient with chronic pain and which would require exceedingly high doses to be effective. They did not mention barbiturates, which are preferable to opiates in causing death and which are used increasingly by compassionate physicians to answer the pleas of their suffering patients, but for which there is no excuse about alleviating pain. Would the criminal law just call the prescription of a lethal dose of barbiturates a reckless act and require conviction? Fortunately, juries, as the authors point out, do not balance these formulas on the head of a pin. When they see the circumstances under which these doctors do help their patients, they choose to nullify the law and would ignore the suggestions made in this article.The authors refer to the “consent” of the patient. They do not mention that these doctors are operating with more than consent; they are administering these medications because suffering patients are begging them to put them out of their pain and the indignities of the dying process. The article discusses the process as though it were the same as consent to elective surgery. These patients—with AIDS, cancer, and hopeless neurological degeneration—are not simply agreeing to a procedure; they are desperately seeking a way out. If the criminal law were to develop criteria for physician aid in dying, certainly one of them should be the active, witnessed, repeated request of such a patient for a certain, quick, painless, gentle death.The third point is that physicians do not face prosecution when administering no treatment to a patient whose life could be saved with treatment but who chooses not to receive it. This has been upheld by the U.S. Supreme Court; no criteria for suffering, alternatives, terminality, justifiability, or unbearability are required. The doctor can stand by while the patient dies what may be a protracted, difficult death, but it is within the law. What matters in this situation is the decision of the patient to refuse treatment, and that is absolute. How ironic that the patient who cannot refuse treatment must, with his or her doctor, jump through all these hoops to achieve a peaceful death.One worries that the physician who must balance the risk of “risky pain relief” against the accusation of recklessness will err in the direction of allowing [End Page 103] the patient to bear the pain rather than help with a dose of analgesics that might be considered beyond the stipulated “risk.”Why don’t we just be honest about it? Allow dying or hopelessly ill patients to make the decision about what they want by passing a carefully defined law allowing euthanasia rather than balancing the risk and trying to determine the “purpose” of the physician’s ministrations. We protect some patients from themselves while allowing others almost complete autonomy to make the choice of ending their lives. The authors were right in saying that proponents of rational laws consider this sheer hypocrisy.Faye Girsh, Executive DirectorHemlock Society U.S.A. Denver, COFaye Girsh misconceives our article’s objective as an “attempt to develop criteria” for the humane physician. Our goal in writing the paper was to analyze the current criminal law framework in the hope of sharpening debate and engendering normative critiques. We readily acknowledge tensions in the current legal framework and would support changes in that framework.Copyright © 1997 The Johns Hopkins University Press... (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.

This is one of a group of papers read at the London Medical Group conference of "Pain: a necessity?",' which was held in Charing Cross Hospital Medical School, London in February 1978. Dr Twycross argues that complete assessment implies the ability not only to make a diagnosis but also to initiate appropriate treatment. Describing the site, severity and quality of the pain is only the first step. A doctor needs to: 1) Be aware of the range of diagnostic possibilities 2) (...) Appreciate the influences of non-physical factors such as mood and morale 3) Be aware of the range of treatemnt options 4) Establish realistic objectives with the patient 5) Reassess at appropriate intervals to review treatment, monitor side-effects, and develop and maintain a good working relationship with the patient. (shrink)