al-Ḥifnī's Muqaddimah fī al-ādāb followed by al-Bishrī's commentary.

Most of the commentaries on Greek authors which circulated in the towns of Egypt during the late Ptolemaic and early Imperial periods ignored the critical and colometrical problems which had engaged the attention of the great Alexandrian grammarians. A few, however, based themselves on texts equipped with signs, included the signs in their lemmata and offered explanations. Such commentaries must be the source of the scattered references to signs in the older marginal scholia in Byzantine manuscripts of Homer, Hesiod, Pindar (...) and the Attic dramatists. The only Byzantine manuscript to transmit a pagan text still equipped with a large number and a variety of signs, namely cod. Venice, Bibl. Marc. gr. 454, is also the only one to transmit scholia with lemmata retaining prefixed signs. Just as texts and scholium-lemmata lost their signs in the course of transmission, so too did references to signs within scholia either disappear or become garbled. At best, a statement about the reasons for affixing a sign would turn into one about the content or style of the verse in question. The few mentions made of the great Alexandrians give no cause for thinking that we ever have a verbatim quotation of an πόμνημα written by one of them in order to explain his own signs. Time and again it is demonstrable that an explanation of a sign's presence against a particular verse goes back to some writer like Aristonicus. What survives of the ancient discussion of Latin literature is exiguous in comparison with the Greek material. (shrink)

In the second book of his Epitoma rei militaris Vegetius sets himself the task of describing the organization of the antiqua legio of the Roman Army, the units into which it was divided, its officers, the arms of its soldiers, and its tactical employment on the field of battle. Interspersed in this account are frequent references to changes that had been subsequently effected and were in operation in the author's lifetime. But although these annotations destroy the synthesis of the book, (...) and the transition from past to present is not always clearly indicated, the disentanglement of Vegetius' own additions from the material provided by his source or sources is not the chief difficulty that confronts the modern historian. For with few exceptions in chapters 4–14 Vegetius describes the antiqua legio in the imperfect, the legion of his own time in the present indicative, with the not infrequent addition of the word ‘nunc’ or ‘hodie.’ The great problem is to discover whether in his account of the antiqua legio the author is referring to any one period of Roman History, and, if so, whether its limits can be exactly defined. Many solutions have been attempted. Some scholars have thought that the period is earlier than Hadrian; the more generally accepted theory is that the antiqua legio can be identified with the legion as it was constituted in the reign of Diocletian. Recently two German historians have subjected the evidence to fresh consideration, and, while one of them agrees with the majority in selecting the age of Diocletian for his answer to the problem, the other believes that he can date the period to which Vegetius is referring to the late second century A.D. (shrink)

Background: The Declaration of Helsinki, the World Medical Association’s statement of ethical guidelines regarding medical research, is published in the three official languages of the WMA: English, French and Spanish.Methods: A detailed comparison of the three official language versions was carried out to determine ways in which they differed and ways in which the wording of the three versions might illuminate the interpretation of the document.Results: There were many minor linguistic differences between the three versions. However, in paragraphs 1, 6, (...) 29, 30 and in the note of clarification to paragraph 29, there were differences that could be considered potentially significant in their ethical relevance.Interpretation: Given the global status of the Declaration of Helsinki and the fact that it is translated from its official versions into many other languages for application to the ethical conduct of research, the differences identified are of concern. It would be best if such differences could be eliminated but, at the very least, a commentary to explain any differences that are unavoidable on the basis of language or culture should accompany the Declaration of Helsinki. This evidence further strengthens the case for international surveillance of medical research ethics as has been proposed by the WMA. (shrink)

This book consists of four major papers written by Peter Achinstein, Peter Geach, Wesley Salmon, and J. L. Mackie. Each of the papers has two commentaries. Achinstein’s paper is commented on by Mary Hesse and R. Harré; Geach’s paper, by Peter Winch and Grete Henry; Salmon’s paper, by D. H. Mellor and L. Jonathan Cohen; Mackie’s paper, by Renford Bambrough and Martin Hollis. Each author of the original paper then replies to his two commentators. All four papers are concerned with (...) some aspect of the concept of explanation. Achinstein’s and Salmon’s papers are extensions and justifications of their previous work. For example, Salmon has argued against Hempel’s account of scientific explanation and has maintained that certain scientific explanations are not arguments of any kind, and that consequently they need not embody the high probabilities that would be required to provide reasonable ground for expectation of the event to be explained. He argues instead that a statistical explanation of a particular event "consists of an assemblage of factors relevant to the occurrence or non-occurrence of the event to be explained, along with the associated probability values". He indicates in the present volume that he does not wish to create the impression "that ability to transmit a mark is any mysterious kind of necessary connection or ‘power’ of the sort Hume criticized in Locke". There is little likelihood that Salmon would be misconstrued in this way. Also there is recent literature to the effect that Locke was clearer on the issues of causality than Hume and that there is nothing "mysterious" in Locke’s notion of powerful particulars. Why are they any more mysterious than the passive particulars preferred by Humeans? (shrink)

Peter Abelard (1079–1142 ce) was the most wide‐ranging philosopher of the twelfth century. He quickly established himself as a leading teacher of logic in and near Paris shortly after 1100. After his affair with Heloise, and his subsequent castration, Abelard became a monk, but he returned to teaching in the Paris schools until 1140, when his work was condemned by a Church Council at Sens. His logical writings were based around discussion of the “Old Logic”: Porphyry's Isagoge, aristotle'S Categories and (...) On Interpretation and boethius'S textbook on topical inference. They comprise a freestanding Dialectica (“Logic”; probably c.1116), a set of commentaries (known as the Logica [Ingredientibus], c. 1119) and a later (c. 1125) commentary on the Isagoge (Logica Nostrorum Petititoni Sociorum or Glossulae). In a work Abelard called his Theologia, issued in three main versions (between 1120 and c.1134), he attempted a logical analysis of trinitarian relations and explored the philosophical problems surrounding God's claims to omnipotence and omniscience. The Collationes (“Debates,” also known as “Dialogue between a Christian, a Philosopher and a Jew”; probably c.1130) present a rational investigation into the nature of the highest good, in which the Christian and the Philosopher (who seems to be modeled on a philosopher of pagan antiquity) are remarkably in agreement. The unfinished Scito teipsum (“Know thyself,” also known as the “Ethics”; c.1138) analyses moral action. (shrink)

Susan D. McCammon and Nicole M. Piemonte offer a thoughtful and thorough commentary on our manuscript entitled “Expanding the use of Continuous Sedation Until Death.” In this reply we attempt to clarify and further defend our position. We show how continuous sedation until death is not a “first resort” but rather a legitimate option among many that should available to terminally ill patients whose life expectancy is less than six months. We also attempt to show that we do not (...) equivocate the meaning of palliative care as the commentators suggested. We argue that the traditional notion of palliative care should move beyond relief of “experienced suffering” to relief of potential suffering for those whose life expectancy is less than six months. Lastly, we challenge the commentator’s position that the realm of ordinary medicine” should be the guide to care, by showing how the notion of ordinary medicine has been successfully challenged in both bioethical scholarship and the courts in a way that shows ordinary medicine to be an evolving concept rather than a static, universal guide. (shrink)

About one third of patients with epilepsy have seizures refractory to the medical treatment. Electrical stimulation mapping is the gold standard for the identification of “eloquent” areas prior to resection of epileptogenic tissue. However, it is time-consuming and may cause undesired side effects. Broadband gamma activity recorded with extraoperative electrocorticography during cognitive tasks may be an alternative to ESM but until now has not proven of definitive clinical value. Considering their role in cognition, the alpha and beta bands could further (...) improve the identification of eloquent cortex. We compared gamma, alpha and beta activity, and their combinations for the identification of eloquent cortical areas defined by ESM. Ten patients with intractable focal epilepsy participated in a delayed-match-to-sample task, where syllable sounds were compared to visually presented letters. We used a generalized linear model approach to find the optimal weighting of each band for predicting ESM-defined categories and estimated the diagnostic ability by calculating the area under the receiver operating characteristic curve. Gamma activity increased more in eloquent than in non-eloquent areas, whereas alpha and beta power decreased more in eloquent areas. Diagnostic ability of each band was close to 0.7 for all bands but depended on multiple factors including the time period of the cognitive task, the location of the electrodes and the patient’s degree of attention to the stimulus. We show that diagnostic ability can be increased by 3–5% by combining gamma and alpha and by 7.5–11% when gamma and beta were combined. We then show how ECoG power modulation from cognitive testing can be used to map the probability of eloquence in individual patients and how this probability map can be used in clinical settings to optimize ESM planning. We conclude that the combination of gamma and beta power modulation during cognitive testing can contribute to the identification of eloquent areas prior to ESM in patients with refractory focal epilepsy. (shrink)

Rationale, aims and objectives To compare the pharmacotherapeutic approaches to diabetic hypertension of family physicians (FPs) and general practitioners (GPs). Methods A retrospective prescription-based study was conducted in 15 out of a total of 20 health centres, involving 115 primary care physicians – 77 FPs and 38 GPs, representing 74% of the primary care physicians of Bahrain. Prescriptions were collected during May and June 2000 to comprise a study population of 1266 diabetic-hypertensive patients. Results As monotherapy, angiotensin-converting enzyme (ACE) inhibitors (...) (37.9%) and β-blockers (38.3%) were the most commonly prescribed classes of antihypertensives by FPs and GPs, respectively. Calcium channel blockers (CCBs) were ranked third by both categories of physicians. For two-drug combinations, a β-blocker and an ACE inhibitor was the combination of choice for both physician categories. Patients managed by the FPs were more likely to receive a β-blocker–CCB combination (17.4 vs. 14.9%) or a diuretic–ACE inhibitor combination (16.7 vs. 11.4%) and less likely to receive a β-blocker–diuretic combination (11.8 vs. 16.7%) than those managed by the GPs. The proportion of patients receiving antihypertensive combinations was 40.6 and 38.5% for FPs and GPs, respectively. While the GPs prescribed CCB as a monotherapy to the elderly most often, the FPs choice was a β-blocker. Diuretics were less preferred by both FPs and GPs. β-Blocker–ACE inhibitor was again the most preferred combination of both FPs and GPs. FPs prescribed CCB–β-blocker combinations more often than GPs (P = 0.01), whereas CCB–ACE inhibitor combinations were less preferred (P = 0.09). A trend towards excessive use of short-acting nifedipine as monotherapy for elderly patients, both by FPs and by GPs, was noticed. Glibenclamide, alone or in combination with metformin, was the foremost antidiabetic drug prescribed by FPs and GPs. Middle-aged (45–64 years) patients seen by GPs were more likely to receive glibenclamide than those treated by FPs (P = 0.001) and less likely to receive gliclazide (P = 0.01). Combinations of a β-blocker with either glibenclamide or insulin were prescribed considerably more often by GPs.Conclusions Within the same practice setting, a substantial difference was observed between FPs and GPs in terms of preference for different classes of drugs in the management of diabetic hypertension. The compliance of both FPs and GPs was suboptimal; overall, the compliance of the FPs was closer to the recommended guidelines, however. Educational programmes should specifically address these inadequacies in order to improve the quality of health care. (shrink)

Upshot: We respond to three main challenges that the commentaries have raised. First, we argue that to deal successfully with the hard problem of consciousness, it is not enough to posit a remedy by which to move beyond the hard problem. Second, we argue that it makes no sense to explain identity. Yet this does not commit us to definitions by fiat. The strategy we pursue here, and in the target article, is not to explain identity but to explain away (...) the appearance of non-identity. Finally, while we are sympathetic to Varela’s call for a paradigm shift in consciousness studies, we argue here, and in the target article, that this call can only be properly successful if the hard problem is dismantled. (shrink)

In lieu of an abstract, here is a brief excerpt of the content: Classics and Complexity in Walden’s “Spring” M. D. USHER In 1843, two years before Henry Thoreau built his cabin at Walden Pond, the Fitchburg Railroad laid down tracks through the woods near the Pond for its line connecting Boston to Fitchburg. The original Fitchburg Line, at 54 miles long, was, until 2010, the longest run in the present -day MBTA Commuter Rail system. And it is one of (...) the oldest railways in New England. By 1900, fortunes swelled and the Fitchburg’s Hoosac Tunnel Line took passengers and goods westward toward Chicago. The Lake Champlain Route connected Boston to points north like Burlington, Vermont. (See Figure 1.) arion 27.1 spring/summer 2019 Figure 1 (left): Advertisement for the Hoosac Tunnel Route in The New England Magazine (Vol. 21, Issue 6, February, 1900). Figure 2 (right): Herbert Wendell Gleason. The Fitchburg Railroad and Walden Pond in winter, Concord, Mass., March 24, 1920. Courtesy Concord Free Public Library. The Railroad was literally a fixture in Thoreau’s landscape. Its tracks pass remarkably close to Walden Pond (Figure 2), and the Fitchburg Line—both its reality and the specter of it—is practically a character in his writing: “I usually go to the village along its causeway, and am, as it were, related to society by this link,” Thoreau writes in “Sounds,” a chapter of Walden that contains what must be one of the most picturesque odes (or laments) to rail travel and commerce in all of American literature: The engine’s whistle, Thoreau complains, pierces the still silence of his idyllic retreat like a screaming hawk circling a farmer’s field, its billows of steam an ominous harbinger of “this travelling demi-god, this cloud-compeller.”1 Thoreau’s frequent, customary walks into Concord along the railroad tracks took him through a heavily excavated stretch of the line known as the Deep Cut, to which he returned again and again each year in early spring, even after leaving the cabin, to observe and to record his observations. The leaf-shaped sand flows and trickling surface erosion caused by melting frost in the banks of the Deep Cut are elaborately described in Thoreau’s chapter in Walden entitled “Spring,” what Laurence Buell calls the “high point of Thoreau’s epic.”2 And yet, in spite of the universal acclaim of this passage as a literary tour de force, it has not received the full attention it deserves. What warrants fresh consideration first and foremost is “Spring”’s deep-rootedness in classical sources. Many classical influences, allusions, and a good deal of etymological word play have gone so far unnoticed. The chapter is also important because it describes, by intimation, what contemporary scientists now call emergence. Emergent phenomena are properties or behaviors that arise in systems as a result of complex, dynamic interactions amongst constituent parts, including changes to a system brought about by human interventions3—not only, e.g., climate change and wildfires, but also traffic patterns and terrorist networks; kidney function in the body; the rings of Saturn. As he tries to capture the essence of the 114 classics and complexity in WALDEN’s “spring” Deep Cut and interpret its significance, Thoreau adumbrates this concept, but also grapples ingeniously with broader issues of perennial concern—the relationship of Nature to Culture, for example, of Wilderness to Civilization, of Science to the Humanities—making “Spring” not only a probing work of eco-criticism and environmental philosophy, but of scientific reflection and poetic experiment as well. In short, Thoreau’s “Spring” is that rare work of classical reception that transmits both literary and scientific insight. Perhaps at this point, in lieu of accolades, it is best to let Thoreau start speaking for himself. What I offer in the following pages is a commentary on the Deep Cut passage from “Spring.” Classical references and aspects of systems theory will be explained and contextualized as they emerge, as it were, from Thoreau’s text. The whole chapter corresponds to pages 289–308 in Cramer’s edition of Walden—26 paragraphs all told, of which only the relevant ones are printed and annotated here. (Transitions and extraneous material are briefly summarized, as needed, in paraphrase... (shrink)

The author reconstructs the theory of F. Varela with relevance to the hard problem of consciousness. This problem was touched by Varela in relatively late period of his work. However, the implications for dissolution of this problem can be found in his earlier works with H. Maturana. Theory of autopoietic systems ties life and cognition together, resulting in natural historical comprehension of consciousness and its functioning. Autopoiesis, understood as network of processes of production of components used as resources for maintaining (...) these processes, sets organizational invariances, distinguishing living system from its milieu. The main criterion of living system is an ability to maintain autopoietic organization while undergoing structural transformations with environment. Structural plasticity leads to multiple realizability of autopoietic organizations, which, in turn, leads to radical conclusion on nature of knowledge. One can distinguish the knower and the known only contingently, as the structure of knowledge reflects cognitive structure of the knower. This intertwinement permits Varela to introduce the enactivist program, which presupposes not simply reform in the scientific research of consciousness but also rethinking the implications of scientific knowledge itself. Cognition is a sensorimotor constitution of the world. Therefore, consciousness is not an object of material nature among other objects but provides our cognitive access to nature. Varela intended to abandon the theoretical approach to the problem of consciousness. His aim was not to provide a new argument. This is a consequence of the enactivist position which, according to theory of autopoiesis, must be applicable to the knower himself. (shrink)

The sporadic nature of Alzheimer's disease argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead during brain development predetermined the expression and regulation of the amyloid precursor protein and its amyloidogenic beta-amyloid product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 ] as well as their transcriptional regulator were elevated in aged (...) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Abeta staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD. (shrink)

Book reviewed in this article: Ezekiel 2: A Commentary on the Book of the Prophet Ezekiel, Chapters 25–48. By Walther Zimmerli. The Prophets, Vol. II: The Babylonian and Persian Periods. By Klaus Koch. Intertestamental Literature by Martin McNamara. Palestinian Judaism and the New Testament by Martin McNamara. Jesus and the World of Judaism. By Geza Vermes. The Rediscovery of Jesus's Eschatological Discourse. By David Wenham. Sexism and God Talk: Towards a Feminist Theology. By Rosemary Ruether. In Memory of (...) Her: A Feminíst Theological Reconstruction of Christian Origins. By Elisabeth Schüssler Fiorenza. Equal Woman: A Christian Feminist Perspective. By Myrtle Langley. Sexual Desire and Love, Origins and History of the Christian Ethic of Sexuality and Marriage. By Eric Fuchs. What Are They Saying about Peace and War? By Thomas A. Shannon. The Dangers of Deterrence: Philosophers on Nuclear Strategy Edited by Nigel Blake and K. Pole. The Cross and the Bomb: Christian Ethics and the Nuclear Debate. Edited by Francis Bridger. Foundations of Ethics. Edited by Leroy S. Rouner. Freud and Human Nature. By Ilham Dilman. What is a Law of Nature By D.M. Armstrong. Bentham. By Ross Harrison. Locke. By John Dunn. Leibniz. By G. Macdonald Ross. Berkeley. By J.O. Urmson. Kant. By Roger Scruton. Marx's Social Critique of Culture. By Louis Dupré. The Hermeneutical Theory of Paul Ricoeur: A Constructive Analysis. By David E. Klemm. Science, Folklore and Ideology: Studies in the Life Sciences in Ancient Greece. By G.E.R. Lloyd. Averroes' Middle Commentaries on Aristotle's ‘Categories’ and ‘De Interpretatione’. Translated, with Notes and Introductions, by Charles E. Butterworth. Miracle in the Early Christian World: A Study in Sociohistorical Method. By Howard Clark Kee. Pagan‐Christian Conflict over Miracle in the 2nd Century. By Harold Remus. Frame of the Universe: A History of Physical Cosmology. By Frank Durham and Robert D. Purrington. The Changing of the Gods. By Frank E. Manuel. English Romanticism: The Grounds of Belief. By John Clubbe and Ernest J. Lovell, Jr. A Short History of the Catholic Church. By J. Derek Holmes and Bernard W, Bickers. The Life and Writings of the Historical Saint Patrick. By R.P.C. Hanson. Rupert of Deutz. By John H. Van Engen. Thomas More. By Anthony Kenny. Luther in Mid‐Career 1521–30. By Heinrich Bornkamm. The Night Battles: Witchcraft and Agrarian Cults in the 16th & 17th Century. By Carlo Ginzburg. Piety and Politics: Religion and the Rise of Absolutism in England, Württemberg, and Prussia. By Mary Fulbrook. Doctor Russell of Maynooth. By Ambrose Macaulay. Paul Cardinal Cullen and the Shape of Modern Irish Catholicism. By Desmond Bowen. The 1980 Synod of Bishops ‘On the Role of the Family’. By Jan Grootaers and Joseph Selling. The Godly Order: Texts and Studies relating to the Book of Common Prayer. By Geoffrey Cuming. (shrink)

Introduction Stored human samples and the establishment of biobanks are increasing in the world. Along with this there are the questions of ethics that arise such as the correct method of obtaining informed consent for research on stored samples and the policies involved in collaborative research using collected samples. This study is an attempt to evaluate the researchers, academics and policy makers' views on these ethical aspects. Methods This was an anonymised study involving a Sri Lankan population of researchers, ethics (...) committee members, and policy makers. A self administered questionnaire was utilised as the study instrument. The questionnaire captured four major areas of interest: demographic characteristics of respondents, their attitudes on informed consent policy, their opinion on rights of collaborating researchers, their attitudes on dealing with international differences in regulatory frameworks. Results The study included 55 responders with 40/55 agreeing that donors should receive the option of giving informed consent for future research, with 31/55 considering multiple- type consent options most appropriate. Regarding the issue of shared samples in collaborative research majority agreed that source country ethics review committee approval was necessary 53/55. Conclusion The study concludes that sample donors should be given the option of giving advance consent to unspecified future research provided that future research is approved by an ethics committee. In collaborative research, it is necessary to involve ethics committees from donor countries in the research approval process. (shrink)

This paper inquires into the nature of intertheoretic relations between psychology and neuroscience. This relationship has been characterized by some as one in which psychological explanations eventually will fall away as otiose, overthrown completely by neurobiological ones. Against this view it will be argued that it squares poorly with scientific practices and empirical developments in the cognitive neurosciences. We analyse a case from research on visual perception, which suggests a much more subtle and complex interplay between psychology and neuroscience than (...) a complete take-over of the former by the latter. In the case of vision, cross-theory influences between psychology and neuroscience go back and forth, resulting in refinement in both disciplines. We interpret this case study as showing that: (1) Mutual co-evolution of psychological and neurobiological theories, exemplifying persisting top-down influences from psychology, is a more empirically adequate way to describe psychoneural theory relations than a view on co-evolution, favoured by reductionists, which regards the cross-theory contributions from psychology as merely heuristically useful with no enduring influence on neurobiological theorizing; (2) In research on vision, discovering (or hypothesizing) the neural basis of functions vindicates psychological approaches, it does not eliminate them; (3) Current work on vision shows that many perceptual phenomena must be understood in terms of dynamical interactions between an observer and his/her environment. Therefore, we argue that internalist characterizations of the visual system must be supplemented with externalist accounts that address these reciprocal observer-environment interactions involved in vision. Such processes seem quite different from (internal) cellular and molecular ones, and as such seem to lie outside the scope of neuroscientific inquiry. We conclude that psychoneural reduction or elimination is implausible as a meta-theoretical prediction of theory choice in empirical work. Instead, this case study of vision shows that both psychology and neuroscience contribute to, and complement one another in the study of visual perception. (shrink)

In the recent past, several papers have pointed to the possibility that tumour removal generates a permissive environment in which tumour growth is potentiated. This phenomenon has been coined “perioperative tumour growth” and whilst it represents a departure in terms of our attitude to the surgical process, this concept was first hinted at by Paget1Sir James Paget (1814–1899) was a surgeon and physiologist who is widely held (along with Rudolph Virchow) to be the father of the science of pathology. Paget (...) described Paget's disease of the nipple as well as Paget's disease of bone. himself. Despite this, the time interval immediately before and after cancer surgery (i.e. the perioperative period) remains an underutilised interval during which chemotherapeutic regimens are rarely implemented. Herein, we present a summarised review of the literature that supports the concept that tumour removal may potentiate the growth of residual neoplastic disease. We also outline current knowledge regarding underlying mechanisms and in this manner highlight potential therapeutic entry points. Finally, we emphasise the urgent need for trials of agents that could protect patients against the harmful host–tumour interactions that may occur during the perioperative period. BioEssays 28: 433–437, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Background In the EU, clinical assessors, rapporteurs and the Committee for Medicinal Products for Human Use are obliged to assess the ethical aspects of a clinical development program and include major ethical flaws in the marketing authorization deliberation processes. To this date, we know very little about the manner that these regulators put this obligation into action. In this paper, we intend to look into the manner and the extent that ethical issues discovered during inspection have reached the deliberation processes. (...) Methods To gather data, we used the Dutch Medicines Evaluation Board database and first searched for the inspections, and their accompanying site inspection reports and integrated inspection reports, related to central marketing authorization applications of drugs submitted to the European Medicines Agency from 2011 to 2015. We then extracted inspection findings that were purely of ethical nature, i.e., those that did not affect the benefit/risk balance of the study. Only findings graded at least major by the inspectorate were included. Lastly, to identify how many of the ethically relevant findings reach the application deliberation processes, we extracted the relevant joint response assessment reports and reviewed the sections that discussed inspection findings. Results From 2011 to 2015, there were 390 processed applications, of which 65 had inspection reports and integrated inspection reports accessible via the database of the Dutch Medicines Evaluation Board. Of the 65, we found ERFs in 37. The majority of the ERFs were graded as major and half of the time it was informed-consent related. A third of these findings were related to research ethics committee processes and requirements. Of the 37 inspections with ERFs, 30 were endorsed in the integrated inspection reports as generally GCP compliant. Day 150 joint response assessment reports and Day 180 list of outstanding issues were reviewed for all 37 inspections, and none of the ERFs were carried over in any of the assessment reports or list of outstanding issues. Conclusion None of the ethically relevant findings, all of which were graded as major or critical in integrated inspection reports, were explicitly carried over to the joint assessment reports. This calls for more transparency in EMA application deliberations on how ERFs are considered, if at all, in the decision-making processes. (shrink)

Open peer commentary on the article “Exploring the Depth of Dream Experience: The Enactive Framework and Methods for Neurophenomenological Research” by Elizaveta Solomonova & Xin Wei Sha. Upshot: This commentary focuses on an ontological claim made by the authors of this target article: that perceiving, imagining and dreaming are inseparable. It explores how best to understand this “inseparability condition.” It is shown that the evidence needed to justify a strict reading of the inseparability condition is lacking, while there (...) is room for a more relaxed rendition of the inseparability condition. The inferred lesson is that in developing an enactive neurophenomenology of dreaming, it is a non-trivial task to achieve clarity about the ontology of dreaming, and its relationship to imagining as well as perceiving. (shrink)

Ḥaydar al-Harawī (d. 825/after 1427) was a significant scholar from Khorasan who migrated to the Ottoman lands. A distinguished student of al-Taftazanī, he earned high regard from Mehmed I and received patronage from him. al-Harawī dedicated his commentary on al-Zamakhsharī’s al-Kashshāf to Mehmed I with exaggerated expressions of praise and provided significant details about his biography in the introduction of the work. After spending many years in Ottoman lands, al-Harawī established contact with Shahrukh, the son of Timur. He rewrote (...) the introduction of Sharḥ al-Kashshāf and ded- icated the work to Shahrukh. This new patronage relationship is evident in the second version of the introduction, where not only the dedication part but also the content was rearranged concerning the new patron’s identity. Important biographical details not found in the first version are included in the second version, making it a crucial source for al-Harawī’s biography. This article brings the second version of the introduction to light for the first time, constructing al-Harawī’s biography by compiling information from both versions. While no specific dates are provided in either version, the duration of al-Harawi’s stay in certain cities is mentioned. Gaps in the narrative were filled based on histori- cal events, allowing for accurate dating of approximately forty years of al-Harawī’s life, from Sarakhs through Shiraz, Tabriz, Shirvan, Bursa, Edirne, and back to Khorasan. This comprehensive overview sheds light on the relationship between scholars and rulers, the influence of political developments on scholarly life, and the intellectual world of a scholar dedicated to the pursuit of knowledge. (shrink)

BackgroundIn research ethics, the most basic question would always be, “which is an ethical issue, which is not?” Interestingly, depending on which ethics guideline we consult, we may have various answers to this question. Though we already have several international ethics guidelines for biomedical research involving human participants, ironically, we do not have a harmonized document which tells us what these various guidelines say and shows us the areas of consensus. In this manuscript, we attempted to do just that.MethodsWe extracted (...) the imperatives from five internationally-known ethics guidelines and took note where the imperatives came from. In doing so, we gathered data on how many guidelines support a specific imperative.ResultsWe found that there is no consensus on the majority of the imperatives and that in only 8.2 % of the imperatives were there at least moderate consensus. Of the 12 clusters, Informed Consent has the highest level of consensus and Research Collaboration and Regulatory Sanctions have the least.ConclusionThere was a lack of consensus in the majority of imperatives from the five internationally-known ethics guidelines. This may be partly explained by the differences among the guidelines in terms of their levels of specification as well as conceptual/ideological differences. (shrink)

Alzheimer's disease is characterized by plaques of amyloid-beta peptide, cleaved from amyloid-beta protein precursor . Our hypothesis is that lifespan profiles of AD-associated mRNA and protein levels in monkeys would differ from mice and that differential lifespan expression profiles would be useful to understand human AD pathogenesis. We compared profiles of AbetaPP mRNA, AbetaPP protein, and Abeta levels in rodents and primates. We also tracked a transcriptional regulator of the AbetaPP gene, specificity protein 1 , and the beta amyloid precursor (...) cleaving enzyme . In mice, AbetaPP and SP1 mRNA and their protein products were elevated late in life; Abeta levels declined in old age. In monkeys, SP1, AbetaPP, and BACE1 mRNA declined in old age, while protein products and Abeta levels rose. Proteolytic processing in both species did not match production of Abeta. In primates, AbetaPP and SP1 mRNA levels coordinate, but an inverse relationship exists with corresponding protein products as well as Abeta levels. Comparison of human DNA and mRNA sequences to monkey and mouse counterparts revealed structural features that may explain differences in transcriptional and translational processing. These findings are important for selecting appropriate models for AD and other age-related diseases. (shrink)

Alzheimer's disease is characterized by formation of neuritic plaque primarily composed of a small filamentous protein called amyloid-beta peptide . The rate-limiting step in the production of Abeta is the processing of Abeta precursor protein by beta-site APP-cleaving enzyme . Hence, BACE1 activity plausibly plays a rate-limiting role in the generation of potentially toxic Abeta within brain and the development of AD, thereby making it an interesting drug target. A phase II trial of the promising LY2886721 inhibitor of BACE1 was (...) suspended in June 2013 by Eli Lilly and Co., due to possible liver toxicity. This outcome was apparently a surprise to the study's team, particularly since BACE1 knockout mice and mice treated with the drug did not show such liver toxicity. Lilly proposed that the problem was not due to LY2886721 anti-BACE1 activity. We offer an alternative hypothesis, whereby anti-BACE1 activity may induce apparent hepatotoxicity through inhibiting BACE1's processing of beta-galactoside alpha-2,6-sialyltransferase I . In knockout mice, paralogues, such as BACE2 or cathepsin D, could partially compensate. Furthermore, the short duration of animal studies and short lifespan of study animals could mask effects that would require several decades to accumulate in humans. Inhibition of hepatic BACE1 activity in middle-aged humans would produce effects not detectable in mice. We present a testable model to explain the off-target effects of LY2886721 and highlight more broadly that so-called off-target drug effects might actually represent off-site effects that are not necessarily off-target. Consideration of this concept in forthcoming drug design, screening, and testing programs may prevent such failures in the future. (shrink)

An account of a language in terms of the sense and reference of its sentences is inadequate and must be supplemented by indicating the point of uttering different sentences. Assuming that a sense and reference account will be given in terms of 'truth' conditions, The article shows that such an account is framed in terms of the notion: member of the class of sentences a language user attempts to utter, Rather than the notion of truth, And that one such account (...) can suffice for two languages. To specify a language completely, We must, In addition to a sense-Reference account, Specify which class of sentences language users attempt to utter. (shrink)

To localize wheat ESTs on chromosomes, 882 homoeologous group 6-specific ESTs were identified by physically mapping 7965 singletons from 37 cDNA libraries on 146 chromosome, arm, and sub-arm aneuploid and deletion stocks. The 882 ESTs were physically mapped to 25 regions flanked by 23 deletion breakpoints. Of the 5154 restriction fragments detected by 882 ESTs, 2043 were localized to group 6 chromosomes and 806 were mapped on other chromosome groups. The number of loci mapped was greatest on chromosome 6B and (...) least on 6D. The 264 ESTs that detected orthologous loci on all three homoeologs using one restriction enzyme were used to construct a consensus physical map. The physical distribution of ESTs was uneven on chromosomes with a tendency toward higher densities in the distal halves of chromosome arms. About 43% of the wheat group 6 ESTs identified rice homologs upon comparisons of genome sequences. Fifty-eight percent of these ESTs were present on rice chromosome 2 and the remaining were on other rice chromosomes. Even within the group 6 bins, rice chromosomal blocks identified by 1-6 wheat ESTs were homologous to up to 11 rice chromosomes. These rice-block contigs were used to resolve the order of wheat ESTs within each bin. (shrink)

We examined if cancer patients' health-related quality of life (HRQoL) scores on the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 are affected by the specific time point, before or during treatment, at which the questionnaire is completed, and whether this could bias the overall treatment comparison analyses. A 'completion-time window' variable was created on three closed EORTC randomised control trials in lung (non-small cell lung cancer, NSCLC) and colorectal cancer (CRC) to indicate when the QLQ-30 was completed (...) relative to chemotherapy cycle dates, defined as 'before', 'on' and 'after'. HRQoL mean scores were calculated using a linear mixed model. Statistically significant differences (P < 0.05) were observed on 6 and 5 scales for 'on' and 'after' comparisons in the NSCLC and two-group CRC trial, respectively. As for the three-group CRC trial, several statistical differences were observed in the 'before' to 'on' and the 'on' to 'after' comparisons. For all three trials, including the 'completion-time window' variable in the model resulted in a better fit, but no substantial changes in the treatment effects were noted. We showed that considering the exact timing of completion within specified windows resulted in statistical and potentially clinically significant differences, but it did not alter the conclusions of treatment comparison in these studies. (shrink)

Peer review of grant applications, it has been suggested, might be distorted by what is popularly termed old boyism, cronyism, or particularism. We argue that the existing debate emphasizes the more uninteresting aspects of the peer review system and that the operation of old boyism, as currently understood would have little effect on the overall direction of science. We identify a phenomenon of cognitive particularism, which we consider to be more important than the institutional cronyism analyzed in previous studies. We (...) illustrate with material drawn from observation of grant-awarding commit tees of the Science and Engineering Research CounciL In the concluding discussion, we explore some of the possible implications for the peer review system. (shrink)

The U.S. Food and Drug Administration's rationale for supporting the development and approval of BiDil for heart failure specifically in black patients was based on under-powered, post hoc subgroup analyses of two relatively old trials , which were further complicated by substantial covariate imbalances between racial groups. Indeed, the only statistically significant difference observed between black and white patients was found without any adjustment for potential confounders in samples that were unlikely to have been adequately randomized. Meanwhile, because the accepted (...) baseline therapy for heart failure has substantially improved since these trials took place, their results cannot be combined with data from the more recent trial amongst black patients alone. There is therefore little scientific evidence to support the approval of BiDil only for use in black patients, and the FDA's rationale fails to consider the ethical consequences of recognizing racial categories as valid markers of innate biological difference, and permitting the development of group-specific therapies that are subject to commercial incentives rather than scientific evidence or therapeutic imperatives. This paper reviews the limitations in the scientific evidence used to support the approval of BiDil only for use in black patients; calls for further analysis of the V-HeFT I and II data which might clarify whether responses to H-I vary by race; and evaluates the consequences of commercial incentives to develop racialized medicines. We recommend that the FDA revise the procedures they use to examine applications for race-based therapies to ensure that these are based on robust scientific claims and do not undermine the aims of the 1992 Revitalization Act. (shrink)

BackgroundThe Netherlands is one of the few countries where euthanasia is legal under strict conditions. This study investigates whether Dutch newspaper articles use the term ‘euthanasia’ according to the legal definition and determines what arguments for and against euthanasia they contain.MethodsWe did an electronic search of seven Dutch national newspapers between January 2009 and May 2010 and conducted a content analysis.ResultsOf the 284 articles containing the term ‘euthanasia’, 24% referred to practices outside the scope of the law, mostly relating to (...) the forgoing of life-prolonging treatments and assistance in suicide by others than physicians. Of the articles with euthanasia as the main topic, 36% described euthanasia in the context of a terminally ill patient, 24% for older persons, 16% for persons with dementia, and 9% for persons with a psychiatric disorder. The most frequent arguments for euthanasia included the importance of self-determination and the fact that euthanasia contributes to a good death. The most frequent arguments opposing euthanasia were that suffering should instead be alleviated by better care, that providing euthanasia can be disturbing, and that society should protect the vulnerable.ConclusionsOf the newspaper articles, 24% uses the term ‘euthanasia’ for practices that are outside the scope of the euthanasia law. Typically, the more unusual cases are discussed. This might lead to misunderstandings between citizens and physicians. Despite the Dutch legalisation of euthanasia, the debate about its acceptability and boundaries is ongoing and both sides of the debate are clearly represented. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Hermeneutics, Neuroscience and PsychiatryMichael T. H. Wong, MBBS, MD, MA, MDiv, PhD, FRCPsych, FRANZCP, FHKAM (bio)Hermeneutic practice in mental health has been a theme in Philosophy, Psychiatry, & Psychology (PPP) since its very beginnings. In this essay I argue that hermeneutics, the theory and practice of interpretation, promotes therapeutic interaction between mental health professionals, patients and their family.Why does this patient present in such a way at this particular (...) point in time? The distressing symptoms are there. The changes in behavior are obvious. Impairments of functions are hurting. A mental illness clearly runs in the family. There were early losses of loved ones, physical abuse at home, bullying by peers and self-medication with drugs and alcohol. Three in four adults with a mental illness first experienced that before they turned 24. The brain goes through major reorganization during adolescence and early adulthood. If synaptic pruning went wrong, psychoses emerged. When stresses activated the hypothalamic–pituitary–adrenal axis the elevated cortisol level impacted the size and function of the hippocampus and amygdala in the genetically vulnerable; anxiety, depression, bipolar, and personality disorders developed. The patient needs a voice/language to describe all these experiences and events and the psychiatrist needs a discourse to make sense of them.Eisenberg laments the swings between "brainlessness" and "mindlessness" in psychiatry. Engel argues for a "biopsychosocial" discourse. The major challenge for psychiatry is how to organize clinical information of different nature (categories, dimensions, narratives; i.e., objective vs. subjective, personal vs. interpersonal) into a coherent and comprehensible account for us all. Mental illnesses are not only neuropsychiatric spectrum disorders but also dysfunctions of social relationship and environmental/ecological adaptation. Psychiatry as a clinical neuroscience per se lacks the semantics to address the rich interactions between the physical, psychological, social, cultural, and spiritual in the illness experience of our patients. Explanation in the diagnostic formulation (objective scientific discourse on cause and effect) and understanding in the patient narrative (subjective ordinary everyday discourse on significance and meaning) are irreducible to each other (Wong, 2018). They instead interact with one another to achieve an integrative formulation, not through merging different discourses into a single assertion/monologue but via the dialectic/dialogue of "explaining more in order to understand better," as Ricoeur puts it, and between "the whole and the parts," as Schleiermacher highlights.This "therapeutic hermeneutic circle" of "explanation vs understanding" and "the whole vs the parts" includes symptoms behavior function and life events. It correlates between bio-psychosociocultural-spiritual dimensions/perspectives and does not reduce them to any particular/single [End Page 13] stance. The whole integrates the parts and the parts enrich the whole. It explains but does not explain away. It understands through an articulation of meaning and significance. This discourse is a multilayered (bio-psycho-social-cultural-spiritual) personal narrative that formulates diagnosis and care in a correlative (linking different voices/discourses) and non-reductive (no particular voice/discourse is prejudiced against) manner that is comprehensible to us all (Wong, 2021).PPP will be an excellent forum for discussing clinical hermeneutics in the future. In this digital era of social media and virtual reality, hermeneutics has the never-ending task to tackle the unprecedented challenges to meaning illness and health posed by polarizing discourses.Michael T. H. Wong Michael T.H. Wong, MBBS, MD, MA, MDiv, PhD, FRCPsych, FRANZCP, FHKAM, is Hon Clinical Professor, Department of Psychiatry, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, HKSAR, China. Michael is Chair, Section of Philosophy & Humanities in Psychiatry, World Psychiatric Association. He is an Organizational Partner & International Lead with The Collaborating Centre for Values-Based Practice in Health and Social Care, St Catherine's College Oxford. He is Advisor to the Chinese Health Foundation of Australia.ReferencesWong M. T. H. (2018). Ricoeur and the third discourse of the person: From philosophy and neuroscience to psychiatry and theology. London: Lexington Books. Google ScholarWong, M. T. H. (2021). Values, meanings, hermeneutics and mental health. In Stoyanov, D., Fulford, K. M. W. F., Stanghellini, G., Van Staden, W., & Wong, M. TH. (Eds.), International perspectives in values-based mental health practice: Case studies and commentaries (pp. 341–349... (shrink)

Each group of selections in this text book is preceded by about ten pages of commentary by Harrington. These commentaries can be read either before the selections as a preparation setting forth the issues, or after the selections as an elucidation, isolating the selection's central concerns. All the selections, with the exception of Kierkegaard's, are from twentieth century thinkers. The contributors include Tillich, Herberg, G. E. Wright, Bultmann, D. M. Bailie, J. J. C. Smart, Wisdom, Hare, Sartre, Barth and (...) Vahanian. The book is divided into three main parts. The first part is basically doctrinal, exploring Biblical themes and contemporary views of revelation, God, man, Jesus, crucifixion, resurrection, and incarnation. The second part deals with aspects of the philosophy of religion including the connection between philosophy and theology, religious language, the existence of God, theistic proofs, and epistemological considerations. The third part, under the heading of "Challenges to Contemporary Man," is a potpourri of theological glamor issues including Existentialism and the death of God. Very often Harrington's commentary provides the reader with the classical aspects of the problem which the contemporary contributer is dealing with. There is a topically organized bibliography of suggested reading. There is no index.--S. O. H. (shrink)

In 2011, the Department of Health and Human Services proposed changes to the regulations that govern human subjects protection in federally funded research. The proposed changes involve modifying inclusion standards for minimal-risk research and removing the necessity of review from certain categories of noninvasive research. All studies would instead be required to comply with privacy protections as initiated by the Health Information Portability and Accountability Act . We argue that relying on HIPAA to protect participants from participation-related risks in noninvasive (...) research is insufficient to protect the autonomy and psychological health of potential research participants. Instead, we suggest a streamlined review format for these categories of research. (shrink)

A countably infinite relational structure M is called absolutely ubiquitous if the following holds: whenever N is a countably infinite structure, and M and N have the same isomorphism types of finite induced substructures, there is an isomorphism from M to N. Here a characterisation is given of absolutely ubiquitous structures over languages with finitely many relation symbols. A corresponding result is proved for uncountable structures.

The United Nations Educational, Scientific and Cultural Organization recently declared transhumance pastoralism as an Intangible Cultural Heritage of Humanity. The notion of heritage seeks to recognize the culture behind the seasonal grazing movements along herding routes, between distant and dissimilar ecosystems. The pastoral families move with their herds from pasturelands used during the winter (winter-lands) to areas pastured during the summer (summer-lands). Whereas this is a key step towards the recognition of the cultural dimension associated to this ancient practice, a (...) relevant feature of transhumance pastoralism is its strong linkage with environmental dynamics. This activity developed in a spatiotemporal and co-evolutionary trajectory, which gave rise to a pastoral territory. A territory is the union or linkage of a meaning with a specific place, that is, the space that is appropriated and valued, both symbolically and instrumentally, by human groups. Hence, the pastoral territory represents the socio-ecological system that integrates a pastoral-based community with the natural environment that it inhabits. We propose a co-evolutionary approach to analyzing some key attributes of transhumant pastoralism, which modulate the socio-ecological interdependence. Based on a study case from Northwest Patagonia, Argentina, we identified and characterized seven attributes: (I) mobility, (II) connectivity, (III) temporal synchrony, (IV) local interdependence, (V) local ecological knowledge, (VI) adaptive capacity legacy, and (VII) mixture of land tenure. We discuss these features as examples that represent keystone socio-ecological attributes for the recognition of transhumant pastoral territories as a biocultural heritage. (shrink)

Shortages of new therapeutics to treat coronavirus disease (COVID-19) have forced clinicians, public health officials, and health systems to grapple with difficult questions about how to fairly allocate potentially life-saving treatments when there are not enough for all patients in need (1). Shortages have occurred with remdesivir, tocilizumab, monoclonal antibodies, and the oral antiviral Paxlovid (2) -/- Ensuring equitable allocation is especially important in light of the disproportionate burden experienced during the COVID-19 pandemic by disadvantaged groups, including Black, Hispanic/Latino and (...) Indigenous communities, individuals with certain disabilities, and low-income persons. However, many health systems have resorted to first-come, first-served approaches to allocation, which tend to disadvantage individuals with barriers in access to care (3). There is mounting evidence of racial, ethnic, and socioeconomic disparities in access to medications for COVID-19 (4, 5). -/- One potential method to promote equitable allocation is to use a weighted lottery, which is an allocation strategy that gives all eligible patients a chance to receive the scarce treatment while also allowing the assignment of higher or lower chances according to other ethical considerations (6). We sought to assess the feasibility of implementing a weighted lottery to allocate scarce COVID-19 medications in a large U.S. health system and to determine whether the weighted lottery promotes equitable allocation. (shrink)

Following a government campaign run by the Independent Commission Against Corruption (ICAC) in 1994, many Hong Kong companies and trade associations adopted written codes of conduct. The research study reported here examines how and why companies responded, and assesses the impact of code adoption on the moral climate of code adopters. The research involved (a) initial questionnaire surveys to which 184 organisations replied, (b) longitudinal questionnaire-based assessments of moral ethos and conduct in a focal sample of 17 code adopting companies, (...) (c) interviews with 33 managers in the focal companies examining the adoption and impact of the codes, and (d) content analysis of 41 company codes of conduct, including those of most focal companies, plus the ICAC model code.While a mixture of prudential and altruistic reasons were given for code adoption, content analysis suggested that the prime motive was corporate self-defence. The prevailing themes were bribery, conflict of interest, insider information, gambling, moonlighting, accuracy of records and misuse of corporate assets. Wider social responsibility tended to be neglected. Companies appeared to have imposed their codes top-down, emphasising disciplinary procedures rather than ethics training, and appointing neither ethics counsellors nor ombuds-people. The longitudinal study over a seven month period suggested that while moral ethos may have declined, overall standards of perceived conduct had not changed. (shrink)

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between (...) studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice. (shrink)

Introduction In 2007, a national review committee was instituted in The Netherlands to review cases of active ending of life for newborns. It was expected that 15–20 cases would be reported. To date, however, only one case has been reported to this committee. Reporting is essential to obtain societal control and transparency; the possible explanations for this lack of reporting were therefore explored. Methods Data on end-of-life decision-making were scrutinised from Dutch nation-wide studies (1995, 2001 and 2005), before institution of (...) the committee. Physicians received a questionnaire about their medical decision-making for stratified samples of deceased infants up to 1 year, drawn from the central death registry. Results In 2005, 58% of all deaths were preceded by an end-of-life decision, compared with 68% in 2001 and 62% in 1995. The use of drugs with a possible life-shortening effect tended to be lower. In 2005, all four cases in the study in which an infants' life was actively ended were preceded by a decision to forego life-prolonging treatment. In three cases, the infant's life expectancy was short; one case involved a longer life expectancy. Discussion The expected number of cases is probably an overestimation due to changes in medical practice such as the tendency to attribute less life-shortening effects to opioids. The lack of reports is probably also associated with requirements in the regulation; it may be difficult to fulfil them due either to time constraints or the nature of the suffering that is addressed. If societal control of active ending of life is considered useful, changes in the regulation may be needed. (shrink)