The feasibility of reversing human aging within a matter of decades has traditionally been dismissed by all professional biogerontologists, on the grounds that not only is aging still poorly understood, but also many of those aspects that we do understand are not reversible by any current or foreseeable therapeutic regimen. This broad consensus has recently been challenged by the publication, by five respected experimentalists in diverse subfields of biogerontology together with three of the present authors, of an article (Ann NY (...) Acad Sci 959, 452–462) whose conclusion was that all the key components of mammalian aging are indeed amenable to substantial reversal (not merely retardation) in mice, with technology that has a reasonable prospect of being developed within about a decade. Translation of that panel of interventions to humans who are already alive, within a few decades thereafter, was deemed potentially feasible (though it was not claimed to be likely). If the prospect of controlling human aging within the foreseeable future cannot be categorically rejected, then it becomes a matter of personal significance to most people presently alive. Consequently, we suggest that serious public debate on this subject is now warranted, and we survey here several of the biological, social and political issues relating to it. BioEssays 24:667–676, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

The feasibility of reversing human aging within a matter of decades has traditionally been dismissed by all professional biogerontologists, on the grounds that not only is aging still poorly understood, but also many of those aspects that we do understand are not reversible by any current or foreseeable therapeutic regimen. This broad consensus has recently been challenged by the publication, by five respected experimentalists in diverse subfields of biogerontology together with three of the present authors, of an article (Ann NY (...) Acad Sci 959, 452–462) whose conclusion was that all the key components of mammalian aging are indeed amenable to substantial reversal (not merely retardation) in mice, with technology that has a reasonable prospect of being developed within about a decade. Translation of that panel of interventions to humans who are already alive, within a few decades thereafter, was deemed potentially feasible (though it was not claimed to be likely). If the prospect of controlling human aging within the foreseeable future cannot be categorically rejected, then it becomes a matter of personal significance to most people presently alive. Consequently, we suggest that serious public debate on this subject is now warranted, and we survey here several of the biological, social and political issues relating to it. BioEssays 24:667–676, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Over recent years, evidence has been accumulating in favour of the free radical theory of aging, first proposed by Harman. Despite this, an understanding of the mechanism by which cells might succumb to the effects of free radicals has proved elusive. This paper proposes such a mechanism, based on a previously unexplored hypothesis for the proliferation of mutant mitochondrial DNA: that mitochondria with reduced respiratory function, due to a mutation or deletion affecting the respiratory chain, suffer less frequent lysosomal degradation, (...) because they inflict free radical damage more slowly on their own membranes. Once such a mutation occurs in a mitochondrion of a non‐dividing cell, therefore, mitochondria carrying it will rapidly populate that cell, thereby destroying the cell's respiratory capability. The accumulation of cells that have undergone this transition results in aging at the organismal level. The consistency of the hypothesis with known facts is discussed, and technically feasible tests are suggested, of both the proposed mechanism and its overall contribution to mammalian aging. (shrink)

On the ethics of extending human life: healthy people have a right to carry on livingHumanity has long demonstrated a paradoxical ambivalence concerning the extension of a healthy human lifespan. Modest health extension has been universally sought, whereas extreme health extension has been regarded as a snare and delusion—a dream beyond all others at first blush, but actually something we are better off without. The prevailing pace of biotechnological progress is bringing ever closer the day when humanity will be able (...) to act on the latter view by rejecting a clear and present opportunity for much longer healthy lives. Indeed, some biogerontologists contend that that day has already arrived, to the extent that our hesitation in embarking on a vigorous “war on ageing” is already delaying the point at which a cure for ageing will be developed. Here I consider whether our present caution concerning the wisdom of truly curing ageing is likely to survive the increased scrutiny that it will receive in coming years as a result of these technical advances. I conclude that it will not, because of its irreconcilability with values that are more deeply held by the large majority of humanity than any values that argue against the quest for a cure. I further conclude that all the major current reasons given for not curing ageing are mere crutches to help us cope with the immutability of ageing that we have been brought up to accept. Our failure to set aside such irrationality is already shortening potential longevity—quite probably of those already alive today—to a staggering degree. Once we realise this, our determination to consign human ageing to history will be second …. (shrink)

The 2013 Rostock Symposium on Systems Biology and Bioinformatics in Aging Research was again dedicated to dissecting the aging process using in silico means. A particular focus was on ontologies, as these are a key technology to systematically integrate heterogeneous information about the aging process. Related topics were databases and data integration. Other talks tackled modeling issues and applications, the latter including talks focussed on marker development and cellular stress as well as on diseases, in particular on diseases of kidney (...) and skin. (shrink)

The US neutrino community gathered at the Workshop on the Intermediate Neutrino Program at Brookhaven National Laboratory February 4-6, 2015 to explore opportunities in neutrino physics over the next five to ten years. Scientists from particle, astroparticle and nuclear physics participated in the workshop. The workshop examined promising opportunities for neutrino physics in the intermediate term, including possible new small to mid-scale experiments, US contributions to large experiments, upgrades to existing experiments, R&D plans and theory. The workshop was organized into (...) two sets of parallel working group sessions, divided by physics topics and technology. Physics working groups covered topics on Sterile Neutrinos, Neutrino Mixing, Neutrino Interactions, Neutrino Properties and Astrophysical Neutrinos. Technology sessions were organized into Theory, Short-Baseline Accelerator Neutrinos, Reactor Neutrinos, Detector R&D and Source, Cyclotron and Meson Decay at Rest sessions.This report summarizes discussion and conclusions from the workshop. (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)

Background: Discussing treatment risks has become increasingly important in medical communication. Still, despite regulations, physicians must decide how much and what kind of information to present. Objective: To investigate patients’ preference for information about a small risk of a complication of colonoscopy, and whether medical and personal factors contribute to such preference. To propose a disclosure policy related to our results. Design: Vignettes study. Setting: Department of Gastroenterology, Academic Medical Centre, the Netherlands. Patients: 810 consecutive colonoscopy patients. Intervention: A home-sent (...) questionnaire containing three vignettes. Vignettes varied in the indication for colonoscopy, complication severity and level of risk. Patients were invited to indicate their wish to be informed and the importance of such information. In addition, sociodemograhic, illness-related and psychological characteristics were assessed. Main outcome measurements: Wish to be informed and importance of information. Results: Of 810 questionnaires, 68% were returned. Patients generally wished to be informed about low-risk complications, regardless of the indication for colonoscopy or the severity of the complication. The level of risk did matter, though (OR = 2.48, SE = 0.28, p = 0.001). The information was considered less important if done for population screening purposes or diagnosis of colon cancer, if the complication was less severe (bleeding) and if the risk was smaller (0.01% and 0.1%). Patients’ information preference was also related to age, mood and coping style. Limitations: Difficulty of vignettes. Conclusions: Patients generally wish to be informed about all possible risks. However, this might become uninformative. A stepwise approach is suggested. (shrink)

Background: More and more quantitative information is becoming available about the risks of complications arising from medical treatment. In everyday practice, this raises the question whether each and every risk, however low, should be disclosed to patients. What could be good reasons for doing or not doing so? This will increasingly become a dilemma for practitioners.Objective: To report doctors’ views on whether to disclose or withhold information on low risks of complications.Methods: In a qualitative study design, 37 respondents were included. (...) Focus group interviews were held with 22 respondents and individual in-depth interviews with 15.Results: Doctors have doubts about disclosing or withholding information on complication risk, especially in a risk range of 1 in 200 to 1 in 10 000. Their considerations on whether to disclose or to withhold information depend on a complicated mix of patient and doctor-associated reasons; on medical and personal considerations; and on the kind and purpose of intervention.Discussion: Even though the degree of a risk is important in a doctor’s considerations, the severity of the possible complications and patients’ wishes and competencies have an important role as well. Respondents said that low risks should always be communicated when there are alternatives for the intervention or when the patient may prevent or mitigate the risk. When the appropriateness of disclosing risks is doubtful, doctors should always tell their patients that no intervention is without risk, give them the opportunity to gather all the information they need or want, and enable them to detect a complication at an early stage. (shrink)

La traduction de l'epistrophe grecque en conversio latine a pu laisser entendre une continuite entre le retour des philosophies grecques neoplatoniciennes et l'evenement religieux proprement chretien de la conversion. Le paradigme en serait le passage de Plotin a Augustin. Mais peut-on oublier que les grecques classiques n'ont pas d'ethique du repentir et que, sans ce rapport au temps de la faute, la constitution de soi n'a ni le meme sens ni le meme lieu? C'est le travail du Centre A.J. Festugiere (...) de Paris X-Nanterre sur les entrecroisements et reprises entre philosophie et religion qui est a l'origine des etudes rassemblees en cet ouvrage. Que nous voyions apparaitre aujourd'hui une nouvelle forme de repentir publique convie a mieux distinguer deux modeles de constitution de soi qui se reconnaissent en ce que l'accent porte tantot sur l'etre et tantot sur le temps. (shrink)

Although narcissists often emerge as leaders, the relationship between leader narcissism and follower performance is ambiguous and often even found to be negative. For women, narcissism seems especially likely to lead to negative evaluations. Since narcissists have the tendency to be impulsive and change their minds on a whim, they may come across as inconsistent. We propose “inconsistent leader behavior” as a new mechanism in the relationship between leader narcissism and follower performance and argue that leader gender plays an important (...) role in whether narcissistic leaders are perceived as inconsistent. Specifically, we expect leader narcissism to have a negative relationship with follower performance through perceived inconsistent leader behavior, especially for female leaders. Thus, we examine leader gender as a personal factor moderating the relationship between narcissism and perceived inconsistent behavior. Also, as perceived inconsistency is likely less problematic when a good relationship exists, we examine leader–member exchange as a contextual condition moderating the relationship between leader behavior and follower performance. We test our moderated mediation model in a multi-source study with 165 unique leader–follower dyads. As expected, leader narcissism was positively related to perceived inconsistent leader behavior, and this relationship was stronger for female leaders. Inconsistent leader behavior was negatively related to follower performance, but only when LMX was low. Our research highlights that perceived behavioral inconsistency can be problematic and—for female leaders—provides an explanation of the negative relation of leader narcissism with follower performance and of the inconsistencies in evaluations of narcissistic leaders’ effectiveness. (shrink)

Ambiguity in the Western Mind, edited with an Introduction by Craig J. N. de Paulo, Senior Editor, et al. New York: Peter Lang Publishers, 2005. Details: Preface by Joseph Margolis and distinguished contributors include John D. Caputo, Camille Paglia, Jaroslav Pelikan, Roland Teske, S.J. et al.

Augustinian Just War Theory and the Wars in Afghanistan and Iraq: Confessions, Contentions and the Lust for Power,edited by Craig J. N. de Paulo, Senior Editor, et al. New York: Peter Lang Publishing, 2011. Details: A work concerning Augustine’s influence on Christian just war theory and the rhetoric of just war theorists from two symposia in addition to an Augustinian critique of the wars. Preface by Most Rev. Sean Cardinal O’ Malley, O.F.M. Cap., Archbishop of Boston. Foreword by Roland J. (...) Teske, S.J. Chapter One is a brief history of Augustine’s influence on the theory. Chapter Two includes a transcript of a symposium on the topic that includes the following distinguished contributors: Avery Cardinal Dulles, S.J., John D. Caputo, Most Rev. Edwin Cardinal O’Brien, Ambassador Thomas Melady, Col. Jack Jacobs, Dr. Joseph Hagan. Chapter Three includes a transcript of a colloquium on the topic that includes the following distinguished scholars and contributors: Joseph Margolis, Frederick Van Fleteren, Brian Kane, et al. (Advance Praise by James J. O’Donnell and Arthur Waldron.). (shrink)

Objectives To evaluate whether the requirement of “minimal risk and burden” for paediatric research without direct benefit to the subjects compromises the ability to obtain data necessary for improving paediatric care. To provide evidence-based reflections on the EU recommendation that allows for a higher level of risk. Design and setting Systematic analysis of the approval/rejection decisions made by the Dutch Central Committee on Research involving Human Subjects (CCMO). Review methods The analysis included 165 proposals for paediatric research without direct benefit (...) that were reviewed by the CCMO between January, 2000, and July, 2007. A separate, in-depth analysis of all drug studies included 18 early phase drug studies and nine other drug studies without direct benefit. Results 11 out of 165 studies were definitively rejected because the CCMO did not regard the risk and/or burden to be minimal. In three of these 11 cases (including two early phase drug studies) the requirement of minimal risk and burden was cited as the only reason for rejection. Four other early phase drug studies also involved risks and/or burdens that were not regarded to be minimal but were nevertheless approved. Conclusions The requirement of minimal risk and burden, aiming to protect research subjects, occasionally leads to rejection of protocols. Early phase drug studies relatively often do not comply with the requirement. Committees may find ways to approve important studies that formally should be rejected, but that is not a desirable solution. The regulatory framework should be revised to make such occasional exceptions to the requirement legitimate and transparent. (shrink)

Kushner and Thomasma have assembled a distinguished group of contributors who are almost all practising clinicians with an interest in medical ethics. The book is well laid out and is divided into two main parts: part one “On caring for patients” and part two “On becoming a `team player’: searching for esprit de corps and conflicts of socialization”. This is a convenient way to think about medical ethics. Part one covers the ethical dilemmas of doctors caring for patients and the (...) many practical problems that arise; this area of medical ethics is what most doctors would consider to be “true” medical ethics. Many doctors would not consider part two to be medical ethics at …. (shrink)

BackgroundThe ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines are widely endorsed but compliance is limited. We sought to determine whether journal-requested completion of an ARRIVE checklist improves full compliance with the guidelines.MethodsIn a randomised controlled trial, manuscripts reporting in vivo animal research submitted to PLOS ONE (March–June 2015) were randomly allocated to either requested completion of an ARRIVE checklist or current standard practice. Authors, academic editors, and peer reviewers were blinded to group allocation. Trained reviewers performed outcome adjudication (...) in duplicate by assessing manuscripts against an operationalised version of the ARRIVE guidelines that consists 108 items. Our primary outcome was the between-group differences in the proportion of manuscripts meeting all ARRIVE guideline checklist subitems.ResultsWe randomised 1689 manuscripts (control: n = 844, intervention: n = 845), of which 1269 were sent for peer review and 762 (control: n = 340; intervention: n = 332) accepted for publication. No manuscript in either group achieved full compliance with the ARRIVE checklist. Details of animal husbandry (ARRIVE subitem 9b) was the only subitem to show improvements in reporting, with the proportion of compliant manuscripts rising from 52.1 to 74.1% (X2 = 34.0, df = 1, p = 2.1 × 10−7) in the control and intervention groups, respectively.ConclusionsThese results suggest that altering the editorial process to include requests for a completed ARRIVE checklist is not enough to improve compliance with the ARRIVE guidelines. Other approaches, such as more stringent editorial policies or a targeted approach on key quality items, may promote improvements in reporting. (shrink)

We estimate that 208,000 deep brain stimulation (DBS) devices have been implanted to address neurological and neuropsychiatric disorders worldwide. DBS Think Tank presenters pooled data and determined that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. The DBS Think Tank was founded in 2012 providing a space where clinicians, engineers, researchers from industry and academia discuss current and emerging DBS technologies and logistical and ethical issues facing the field. (...) The emphasis is on cutting edge research and collaboration aimed to advance the DBS field. The Eighth Annual DBS Think Tank was held virtually on September 1 and 2, 2020 (Zoom Video Communications) due to restrictions related to the COVID-19 pandemic. The meeting focused on advances in: (1) optogenetics as a tool for comprehending neurobiology of diseases and on optogenetically-inspired DBS, (2) cutting edge of emerging DBS technologies, (3) ethical issues affecting DBS research and access to care, (4) neuromodulatory approaches for depression, (5) advancing novel hardware, software and imaging methodologies, (6) use of neurophysiological signals in adaptive neurostimulation, and (7) use of more advanced technologies to improve DBS clinical outcomes. There were 178 attendees who participated in a DBS Think Tank survey, which revealed the expansion of DBS into several indications such as obesity, post-traumatic stress disorder, addiction and Alzheimer’s disease. This proceedings summarizes the advances discussed at the Eighth Annual DBS Think Tank. (shrink)

Le Socrate de Xénophon et la démocratie présente une interprétation nuancée du témoignage de Xénophon sur l’attitude de Socrate à l’endroit de la démocratie athénienne. Cette étude conteste les interprétations qui ont été trop restrictives dans le choix des témoignages et trop négatives dans leurs conclusions. Elle tient compte, d’une part, des différents paramètres qui permettent de définir la démocratie ; d’autre part, des réalités de la démocratie athénienne. Les principaux textes pertinents proviennent des Mémorables. Nous traitons de la nature (...) de cet ouvrage et de la façon dont il expose l’attitude de Socrate à l’endroit des lois et des institutions du régime démocratique, notamment l’assemblée et le tirage au sort. Cette étude présente enfin une interprétation plus nuancée de la propre attitude de Xénophon à l’endroit de la démocratie, attitude qui a elle-même influé sur la façon dont on a, par le passé, évalué l’attitude de son Socrate.Xenophon’s Socrates and Democracy offers a balanced interpretation of Xenophon’s evidence for Socrates’ attitude to the Athenian democracy, arguing against interpretations that have been too selective in their evidence and too negative in their conclusions. It takes due account of the various parameters that define democracy and the realities of Athenian democracy. The main evidence is from Memorabilia. There is discussion of nature of this work, and then of how it expresses Socrates’ attitude to the laws of the democracy and other processes such as sortition and the assembly. The paper also offers a more balanced interpretation of Xenophon’s own attitude to democracy, which has influenced past assessments of the attitude of his Socrates. (shrink)

L'interprétation de l'eschatologie paulinienne est dominée par la question de son rapport avec l'apocalyptique juive. Les points communs, soulignés par J.C. Beker à la suite de E. Käsemann, ne sont pas contestables, mais ne doivent pas occulter des différences notables, qui tiennent à la prééminence du Christ dans la vision paulinienne des événements de la fin. Ni l'attente ni le retard de la parousie ne semblent avoir eu, quoi qu'on en dise, d'influence décisive sur la pensée de l'Apôtre, mais bien (...) plutôt la réconciliation avec Dieu par la Croix et l'inauguration d'une humanité nouvelle dans la résurrection du Christ.Les lettres deutéropauliniennes ne rnodifient pas fondamentalement cette eschatologie, si ce n'est qu'elles accentuent encore l'emprise de la christologie sur la vision de la fin : à ceux qui attendent les ascensions célestes promises par la littérature apocalyptique, Paul répond qu'ils possèdent déjà leur être ressuscité avec le Christ, qui trône bien au-dessus de tous les être célestes. Ses idées sur le jugement dernier et la rétribution finale sont parfois dépendantes de celles du judaïsme, souvent imprécises et limitées, mais c'est toujours sa connaissance du Ressuscité, second Adam, qui conduit sa réflexion et l'aide à déchiffrer le destin final de l'humanité dans le Christ. The interpretation of pauline eschatology is dominated by the question of its rapport with Jewish apocalypse. The common points, underlined by J.C. Beker following E. Käsemann, cannot be contested, but should not hide the notable differences, which are based on the pre-eminence of Christ in the Pauline vision of the final events. Neither the expectation nor the delay of the Parousia does not seem to have had, despite what is said, a decisive influence on the Apostle’s thinking. He was concerned more about reconciliation with God through the cross and the inauguration of a new humanity by the resurrection of Christ.The deuteropauline letters do not fundamentally modify this eschatology, except in so far as they accentuate the dominance of Christology on the vision of the end. For those who await the celestial ascensions promised by apocalyptic literature, Paul answers that they already possess their resurrected being with Christ, who sits well above are celestial beings. These ideas on the Last Judgement and the final retribution are sometimes dependent on those of Judaism, often imprecise and limited, but it is always Paul's knowledge of the Resurrected, the second Adam, which directs his reflection and helps to decipher the final destiny of humanity in Christ. (shrink)

At the beginning of 2020, COVID-19 became a global problem. Despite all the efforts to emphasize the relevance of preventive measures, not everyone adhered to them. Thus, learning more about the characteristics determining attitudinal and behavioral responses to the pandemic is crucial to improving future interventions. In this study, we applied machine learning on the multi-national data collected by the International Collaboration on the Social and Moral Psychology of COVID-19 (N = 51,404) to test the predictive efficacy of constructs from (...) social, moral, cognitive, and personality psychology, as well as socio-demographic factors, in the attitudinal and behavioral responses to the pandemic. The results point to several valuable insights. Internalized moral identity provided the most consistent predictive contribution—individuals perceiving moral traits as central to their self-concept reported higher adherence to preventive measures. Similar was found for morality as cooperation, symbolized moral identity, self-control, open-mindedness, collective narcissism, while the inverse relationship was evident for the endorsement of conspiracy theories. However, we also found a non-negligible variability in the explained variance and predictive contributions with respect to macro-level factors such as the pandemic stage or cultural region. Overall, the results underscore the importance of morality-related and contextual factors in understanding adherence to public health recommendations during the pandemic. (shrink)