End-of-life decision making is fraught with ethical challenges. Withholding or withdrawing life support therapy is widely considered ethical in patients with high treatment burden, poor premorbid status, or significant projected disability even when such treatment is not ?futile.? Whether such withdrawal of therapy in the aftermath of attempted suicide is ethical is not well established in the literature. We provide a clinical vignette and propose criteria under which such withdrawal would be ethical. We suggest that it is appropriate to withdraw (...) life support, regardless of the cause of the critical illness or disability, when the following criteria are met: (1) Surrogates request withdrawal of care and the adequacy of surrogates is confirmed, (2) an external reasonability standard is met, (3) passage of time, perhaps 72 hours, to allow certainty regarding the patient's wishes, and (4) psychiatric morbidity should be considered as grounds for withdrawal only in truly treatment-refractory cases. Fundamentally, we believe the question to ask is, ?If this were not an attempted suicide, would a request to withdraw care be reasonable?? We believe that under these circumstances, such withdrawal of life support, even in an individual who has attempted suicide, does not constitute physician assistance with suicide and is distinct from physician aid-in-dying in several important respects. (shrink)

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)

We are grateful for the careful reading and insightful responses of the several peer commentaries to our proposed approach to requests to withhold or withdraw life support therapies among patients...

v. 1. Life of Thomas Paine, by W.M. Van der Weyde.--v. 2. Early essays. Common sense. The American crisis, I-IV.--v. 3. The American crisis, V-XIII. Patriotic papers.--v. 4. Political pamphlets.--v. 5. Open letters. Dissertations.--v. 6. Rights of man.--v. 7. Rights of man, concluded. Miscellaneous essays.--v. 8. The age of reason.--v. 9. Theological discussions.--v. 10. Miscellany. Songs and rhymes. Index.

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)

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.

When someone steps on your toe on purpose, it seems to hurt more than when the person does the same thing unintentionally. The physical parameters of the harm may not differ—your toe is flattened in both cases—but the psychological experience of pain is changed nonetheless. Intentional harms are premeditated by another person and have the specific purpose of causing pain. In a sense, intended harms are events initiated by one mind to communicate meaning (malice) to another, and this could shape (...) the recipient’s experience. This study examined whether self-reported pain is indeed higher when the events producing the pain are understood as intentionally (as opposed to unintentionally) caused by another person. Although pain was traditionally conceived to be solely physical in nature (Aydede, 2005), its experience varies substantially with psychological context. The placebo analgesia effect, for example, is the reduction of pain without a change in physical stimulation when context, expectations, or sugar pills challenge the interpretation of a sensation as painful (e.g., Fields, 2008). The nocebo effect, in turn, is the experience of pain without any physical stimulation—as when participants report headaches when told that a (nonexistent) electric current is passing through their heads (Schweiger & Parducci, 1981). These variations in pain experience seem to depend on the meaning of the stimulus: A sugar pill is meant to decrease pain, whereas electric current is meant to increase pain. In an interpersonal context, the meaning of an action is derived from the would complete. perceiver’s perceptions of the actor’s intention (Clark, 1996). (shrink)

Local food systems are growing, and little is known about how the constellation of farms and markets change over time. We trace the evolution of two local food systems over six years, including a dataset of over 2690 market connections between 1520 locations. Longitudinal social network analysis reveals how the architecture, actor network centrality, magnitude, and spatiality of these supply chains shifted during the 2012–2018 time period. Our findings demonstrate that, despite growth in the number of farmers’ markets, grocery stores, (...) farms and restaurants in both counties, each local food system also experienced high turnover rates. Over 80% of the market connections changed during the study period. Farms, farmers’ markets, and grocery stores showed a 40–50% ‘survival’ rate, indicating their role in sustaining local food systems over longer time periods. Other actors, such as restaurants, had a much higher turnover rate within the network. Both food systems became more close-knit and consolidated as the center of gravity for both local food systems pulled away from urban areas toward rural farmland. Evidence of both growth and decay within local food systems provides a new understanding of the social networks behind local food markets. (shrink)

This paper focuses on the possibility of conceiving a form of ontological nihilism, starting from D. M. Armstrong’s combinatorialism. This possibility has been suggested by Efird and Stoneham, by means of proposing an alternative strategy to the ‘subtraction argument’. They claim that it is possible to sustain such nihilism trough the concepts of construction and totality state of affairs. However, this hypothesis will require the acceptance of non-instanciated universals, that is, platonic universals. Yet this is opposite to requirements that are (...) basic for a combinatorial theory, which should uphold that universals exist only in their instantiations. Then, the assumption of platonic universals results in high costs for a combinatorial naturalism, according to which only exists what is located in space and time. (shrink)

Believing in God requires not only a leap of faith but also an extension of people’s normal capacity to perceive the minds of others. Usually, people perceive minds of all kinds by trying to understand their conscious experience (what it is like to be them) and their agency (what they can do). Although humans are perceived to have both agency and experience, humans appear to see God as possessing agency, but not experience. God’s unique mind is due, the authors suggest, (...) to the uniquely moral role He occupies. In this article, the authors propose that God is seen as the ultimate moral agent, the entity people blame and praise when they receive anomalous harm and help. Support for this proposition comes from research on mind perception, morality, and moral typecasting. Interestingly, although people perceive God as the author of salvation, suffering seems to evoke even more attributions to the divine. (shrink)

Thomas Paine often declared himself a citizen of the world. This Norton Critical Edition presents Paine and his writing within the transatlantic and global context of the revolutionary ideas and actions of his time. Thomas Paine's loyalties were with universal and self-evident principles rather than with a particular group or nation, and it is this dimension that informed his most important works. This Norton Critical Edition shows how Paine's fury at the British Empire, including its injustices to South Asians and (...) Africans, shaped his first best seller, Common Sense, and how his direct involvement with the French Revolution pushed his ideas toward a unique form of democratic radicalism. Together with his rejection of organized religion, Paine's radicalism resulted in his being one of the most hated men in both monarchial Britain and republican America. This volume includes J. M. Opal's introduction, "Thomas Paine and the Revolutionary Enlightenment, 1770s-90s," which provides essential biographical and historical details across three tumultuous decades. Paine's most important works-from Common Sense (1776) through Agrarian Justice (1796)-are reprinted and are accompanied by explanatory annotations. Supporting materials include a wide range of documents from the turbulent years following the publication of both Common Sense and the Declaration of Independence. These include Pennsylvania's gradual emancipation statute of the 1780s, an ex-slave's impassioned call for revolutionary violence against European imperialists and masters, and a British conservative's witty rejoinder to Paine's vision of a brave new world. Four major interpretations of Paine's work are provided by Nathan R. Perl-Rosenthal, Robert A. Ferguson, Gary Kates, and Gregory Claeys. A Selected Bibliography is also included. (shrink)

I. Rights of man; being the first volume of an entirely new and unabridged issue. Ed. by Hypatia Bradlaugh Bonner, with a biographical and critical introduction by John M. Robertson. -- II. The age of reason; being the second volume of an entirely new and unabridged issue of the chief works of Thomas paine. Ed., with historical introduction, by Hypatia Bradlaugh Bonner.

Providing nursing care for people with dementia residing in long-term care facilities poses specific challenges regarding pain practices. With underlying communication barriers unique to dementia pathologies, this population is often unable to communicate verbal sentiments and descriptions of pain. In turn, nurses caring for older persons with dementia have difficulty assessing, managing and treating pain. Objectivity is an imperative factor in healthcare pain practices; however, it is difficult to objectively evaluate someone who cannot accurately communicate their experience of pain. Therefore, (...) the authors believe that subjectivity is also an essential part of evaluating the person with dementia's experience of pain. In this critical reflection, the authors explore objectivity and subjectivity in relation to pain practices for dementia in long-term care. A historical summary of pain is provided outlining the evolution of objectivity and subjectivity related to pain practices. The authors discuss the complexities of assessing and managing pain and offer a new perspective about the role of objectivity (and co-existence of subjectivity) for nurses treating pain in the older adults with dementia. (shrink)

Two experiments, one on school-aged children and one on adults, explored the mechanisms underlying responses to an image prime followed by graspable objects that were, in certain cases, dangerous. Participants were presented with different primes and objects representing two risk levels . The task required that a natural/artifact categorization task be performed by pressing different keys. In both adults and children graspable objects activated a facilitating motor response, while dangerous objects evoked aversive affordances, generating an interference-effect. Both children and adults (...) were sensitive to the distinction between biological and non-biological hands, however detailed resonant mechanisms related to the hand-prime gender emerged only in adults. Implications for how the concept of “dangerous object” develops and the relationship between resonant mechanisms and perception of danger are discussed. (shrink)

A monolithic model that ignores functional and topographic distinctions among its components has dominated clinical accounts of pain behavior. This model contributes to a pretence of knowledge that affects the treatment of sufferers. This commentary addresses the role of the target article in correcting knowledge-pretence and introduces a complementary caveat about evolutionary psychology concepts.

The target articles by blumberg et al. and berkley reflect some of the recent major theoretical and clinical advances in two areas of pain research. These two articles also represent two very different approaches to which type of variables are considered relevant to the study of pain. These different approaches are contrasted in the context of the different emphases in pain and pleasure research.

A decade ago, conventional wisdom in the medical establishment was that physicians treating chronic pain with opioid analgesics were at a substantial risk of being sanctioned for overprescribing by state medical regulatory boards. Dozens of articles written since have alluded to this risk as an obstacle to effective pain re1ief. In the early 1990s, a number of high profile cases in which physicians were disciplined by regulatory boards for overprescribing to patients with chronic pain were reported in the press. Although (...) the board actions in many of these cases were eventually overturned by state judiciaries, the publicity heightened practitioners’. sensitivity to the regulatory risks associated with prescribing opioids.A review of the available data on state medical board actions nationwide for the period from 1990 to 1996 reveals that the perception of regulatory risk far exceeds the reality. Indeed, relatively few of the disciplinary actions taken for overprescribing by state medical boards in any given year directly concern the treatment of chronic pain—malignant or nonmalignant—in patients. (shrink)

When a person in pain seeks medical attention, but his doctors cannot help him, a quest begins for alternative treatment, with its attendant imperative to identify the difference between genuine solace and snake oil. This is the task undertaken by Scott Waterman, and the situation faced by millions of people in chronic pain for whom conventional medicine proves ineffective, and who likewise then embark on a desperate search for comfort.Alternative treatments sit on a spectrum of empirical plausibility, from some like (...) hypnosis or mindfulness with demonstrable mechanisms of action in the brain and nervous system to others like Reiki and craniosacral therapy that purport to channel mysterious energy fields beyond the... (shrink)

Over the past few years, over a dozen states have proposed, and almost as many have passed, something referred to as the Pain-Capable Unborn Child Protection Act, a piece of legislation that makes abortion impermissible once fetal pain is possible and that further stipulates the fetus can feel pain at or before 20 weeks of gestation. Some very important questions immediately relevant to the abortion debate, perhaps even to the more complex issue of fetal rights, are raised by this legislation, (...) especially because it would impinge on the second-trimester abortion rights guaranteed by Roe. We first inquire whether the claim of fetal pain perception at or before 20 weeks is true and how such a claim should be substantiated. Next, we inquire whether the fetal capacity to experience pain, at whatever stage of development, reflects on the morality of abortion and whether it should be at all relevant to determining its legality. Finally, we would like to explore the implications that a commitment to a pain-related or sentience criterion of rights might have for a pro-life agenda. (shrink)

ABSTRACT:Biomedical and philosophical traditions postulate the experience of pain either as quantifiable or as sociocultural phenomena. This critical assessment offers a close reading of Lara Parker’s Vagina Problems: Endometriosis, Painful Sex, and Other Taboo Topics (2020) and Abby Norman’s Ask Me About My Uterus: A Quest to Make Doctors Believe in Women’s Pain (2018), analyzing the authors’ use of language as a tool to comprehend and communicate pain. Norman’s and Parker’s memoirs narrate the lived experience of endometriosis, a condition diagnosed (...) almost exclusively in women and characterized by chronic pain. The essay looks at how metaphors are employed in living and narrating endometriosis in medical, social, and cultural settings that are highly skeptical of women’s pain and trace a shift in the use of pain metaphors towards an acceptance of the pain experience, which is conceptualized as empowering by the climax of the narrative. (shrink)

In this paper, I explore how our experience of pain and suffering structure our experience over time. I argue that pain and suffering are not as easily dissociable, in living and in conceptual analysis, as philosophers have tended to think. Specifically, I do not think that there is only a contingent connection between physical pain and psychological suffering. Rather, physical pain is partially constitutive of existential suffering. My analysis is informed by contemporary thinking about pain and suffering as well as (...) Indian Buddhist philosophy. (shrink)

This paper focuses on the possibility of conceiving a form of ontological nihilism, starting from D. M. Armstrong’s combinatorialism. This possibility has been suggested by Efird and Stoneham, by means of proposing an alternative strategy to the ‘subtraction argument’. They claim that it is possible to sustain such nihilism trough the concepts of construction and totality state of affairs. However, this hypothesis will require the acceptance of non-instanciated universals, that is, platonic universals. Yet this is opposite to requirements that are (...) basic for a combinatorial theory, which should uphold that universals exist only in their instantiations. Then, the assumption of platonic universals results in high costs for a combinatorial naturalism, according to which only exists what is located in space and time. (shrink)

1. First person authority: the received explanation Over a wide range of psychological attributes, a mature speaker seems to enjoy a defeasible form of authority on how things are with him. The received explanation of this is epistemic, and rests upon a cognitive assumption. The speaker’s word is a authoritative because when things are thus-and-so with him, then normally he knows that they are. This is held to be because the speaker has direct and privileged access to the contents of (...) his consciousness by means of introspection, conceived as a faculty of inner sense. Like perceptual knowledge, introspective knowledge is held to be direct and non-evidential. Accordingly, the first-person utterances ‘I have a pain’, ‘I believe that p’, ‘I intend to V’ are taken to be descriptions of what is evident to inner sense. Many classical thinkers held such subjective knowledge to be not only immediate, but also infallible and indubitable. The challenge to the received conceptions came from Wittgenstein. He denied the cognitive assumption, arguing that it cannot be said of me at all (except perhaps as a joke) that I know that I am in pain. For what is that supposed to mean — except perhaps that I am in pain?1 If it makes no sense to say that one knows that one is in pain, then the epistemic explanation is a non-starter, since it explains the special authoritative status of a person’s avowal of pain by reference to the putative fact that the subject of pain knows, normally knows, or cannot but know, that he is in pain when he is. It is important to note that Wittgenstein did not mechanically generalize the case of pain across the whole domain of firstperson utterances. The case of pain constitutes only one pole of a range of such utterances. Avowals and averrals of belief and intention approximate the other pole, and require independent analysis and grammatical description. (shrink)

In the Eurowest pain is discursively framed as something that elides discourse and therefore is outside language. In this framing, pain, as outside language, is given asocial and ahistorical status understood to be beyond human construction. Indeed, played out in systems of belief and practice, pain acts as a medium for reciprocal relations with the metaphysical other since it too is understood as originating and sharing a part in the 'authentic' or 'real' from which the metaphysical, and therefore truth, is (...) understood to emerge. Understood as part of this domain, pain is linked to truth and therefore understood to be a means to truth; hence the use of torture to secure the truth. With this kind of discursive framing, this book works to make apparent the rhetorical play of pain demonstrating its social and political imperatives. (shrink)