Phosphatidylinositol‐3‐kinases (PI3Ks) are lipid kinases that produce 3‐phosphorylated derivatives of phosphatidylinositol upon activation by various cues. These 3‐phosphorylated lipids bind to various protein effectors to control many cellular functions. Lipid phosphatases such as phosphatase and tensin homolog (PTEN) terminate PI3K‐derived signals and are critical to ensure appropriate signaling outcomes. Many lines of evidence indicate that PI3Ks and PTEN, as well as some specific lipid effectors are highly compartmentalized, either in plasma membrane nanodomains or in endosomal compartments. We examine the evidence (...) for specific recruitment of PI3Ks, PTEN, and other related enzymes to membrane nanodomains and endocytic compartments. We then examine the hypothesis that scaffolding of the sources (PI3Ks), terminators (PTEN), and effectors of these lipid signals with a common plasma membrane nanodomain may achieve highly localized lipid signaling and ensure selective activation of specific effectors. This highlights the importance of spatial regulation of PI3K signaling in various physiological and disease contexts. (shrink)

Adler and Barnett demonstrate how changes occurring in international politics create the nostalgia of security communities, a concept made prominent by Karl Deutsch nearly forty years ago.

This article analyzes trends in drug shortages in the US and Germany, the largest pharmaceutical market in Europe, between 2016 and 2023. It assesses the commonalities and differences between the countries in terms of active substances in shortage, time duration in shortage, and cyclic trends.

Dans la première partie de L'unique fondement possible d'une démonstration de l'existence de Dieu (1763), Kant propose un argument de type ontologique qu'il avait déjà formulé dans ses écrits de 1755. La présente contribution voudrait examiner continuité et changements dans les différentes formulations. Contrairement à ce que soutiennent d'autres chercheurs, j'entends montrer que l'argument de Kant se présente, dès le départ, comme une alternative à celui des auteurs de la tradition wolffienne. Cette innovation comporte certaines difficultés théoriques qui apparaissent clairement (...) dans le texte de 1763. Tout en confirmant la conviction que l'argument ontologique de la tradition wolffienne n'est pas démonstratif, Kant estime ne pas disposer d’un argument alternatif complet, mais seulement de son fondement. (shrink)

Etait-il mieux pour les hommes qu'il acceptaient une conpeptior mythique de la réalité et de la vie, en refusant les données et les méthodes de là science? Cette suggestion n'est pas justifiée sur le plan historique et non plus sur le plan critique. De dilemme même de mythe et science est fictif et peut faus- sear l'état réel des problèmes. On aboutit à la conclusion, qu'il faut essayer de réaliser une synthèse du mythe avec les procédés critiques de la raison (...) scientifique, pour satisfaie la multiplicité des demandes de l'âme humaine. (shrink)

Narcissism is a truly Janusian phenomenon, consisting of both narcissistic grandiosity, exhibitionism, admiration-seeking, boldness, and dominance on the one hand, and narcissistic vulnerability, introversion, withdrawal, hypersensitivity, and anxiety on the other hand. While there is broad consensus that these two seemingly contradictory faces of narcissism can be empirically discerned and have different implications for psychological functioning and mental health, there is not yet agreement on whether grandiose and vulnerable narcissism should be regarded as independent traits or as two manifestations of (...) one personality trait. Previous research indicates that both views hold true when the level of grandiosity is considered a moderating factor: while grandiose and vulnerable narcissism are largely unrelated in the range of normal personality variation, they are correlated in the range of high grandiosity ( Jauk et al., 2017b ). Here, we replicate and extend this work in an independent sample ( N = 891) using a more comprehensive narcissism inventory grounded in a new trifurcated model of narcissism. The trifurcated model partitions narcissism into three main personality dimensions: agentic extraversion, antagonism, and neuroticism. We found a significant breakpoint in the association between narcissistic grandiosity and vulnerability at 75% cumulative frequency of grandiosity. While grandiosity and vulnerability are unrelated below this breakpoint ( r = 0.02), they are strongly correlated above ( r = 0.45). In the lower range of grandiose narcissism, grandiosity draws more upon agentic extraversion and is largely associated with mental health. In the upper range, however, grandiosity is more strongly linked to antagonism and is substantially associated with fear, negative affect, and depression. These findings provide evidence for the view that grandiose and vulnerable narcissism are distinct traits at lower levels of grandiosity, but blend into an antagonistic core with signs of psychological maladjustment at higher levels. Implications for research on narcissism as a personality trait, as well as clinical practice, are discussed. (shrink)

We consider fragments of uniform reflection for formulas in the analytic hierarchy over theories of second order arithmetic. The main result is that for any second order arithmetic theory $T_0$ extending $\mathsf {RCA}_0$ and axiomatizable by a $\Pi ^1_{k+2}$ sentence, and for any $n\geq k+1$, $$\begin{align*}T_0+ \mathrm{RFN}_{\varPi^1_{n+2}} \ = \ T_0 + \mathrm{TI}_{\varPi^1_n}, \end{align*}$$ $$\begin{align*}T_0+ \mathrm{RFN}_{\varSigma^1_{n+1}} \ = \ T_0+ \mathrm{TI}_{\varPi^1_n}^{-}, \end{align*}$$ where T is $T_0$ augmented with full induction, and $\mathrm {TI}_{\varPi ^1_n}^{-}$ denotes the schema of transfinite induction up (...) to $\varepsilon _0$ for $\varPi ^1_n$ formulas without set parameters. (shrink)

Pourquoi recourir à la pensée de Dietrich Bonhoeffer pour formuler une contribution philosophique au problème de la tolérance? Et, de surcroît, en dialogue avec la phénoménologie? Homme de pensée et d’action, Bonhoeffer n’est, à proprement parler, ni un phénoménologue ni un penseur de la tolérance. Il est, toutefois, légitime d’envisager sa lutte contre le totalitarisme, tant sur le plan théologique que politique, comme un cas limite susceptible de relever du questionnement sur la nature et la portée de la tolérance elle-même. (...) Et cela en raison du paradoxe auquel Bonhoeffer s’expose dans la tentative de putsch visant l’élimination du Führer à laquelle il participe : la violation non seulement de la loi, mais d’un commandement divin – « tu ne tueras pas » – que Bonhoeffer justifie au nom de sa foi en Dieu. Notre hypothèse de lecture nous conduit dès lors à consacrer une attention particulière à sa thèse d’habilitation, Akt und Sein, où Bonhoeffer formule une critique originale de la phénoménologie notamment heideggérienne, inspirée par la theologia crucis de tradition luthérienne : renonçant à toute tentative d’autodétermination, l’homme, pour Bonhoeffer, ne peut se comprendre que par une ouverture radicale à la transcendance qui coïncide, en dernière instance, avec la dimension authentiquement personnelle de l’homme lui-même ainsi que de la relation entre l’homme et Dieu. (shrink)

Dans le dernier quart du xix e siècle, l’ambition d’une philosophie scientifique inspire la Psychologie vom empirischen Standpunkt de Franz Brentano. Appelée à refonder sur des bases empiriques l’univers de l’être, cette forme nouvelle de psychologie réactualiserait ainsi, en un sens, un certain héritage de la métaphysique ancienne. Et Brentano parviendrait à assembler dans une même vision systématique les sources de la pensée grecque, en particulier aristotélicienne, et moderne. Mais peut-on vraiment considérer Brentano comme un aristotélicien en raison de son (...) projet psychologique? La question est bien connue et comme Franco Volpi, entre autres, le soutient, il semblerait que l’orientation épistémologique de la psychologie brentanienne ne trouve pas dans l’aristotélisme son véritable motif directeur. Une autre lecture est toutefois possible à nos yeux, si nous considérons qu’à aucun moment Brentano ne prétend faire de la psychologie un moyen pour revenir à Aristote. C’est notre hypothèse de recherche qui nous conduit à lire avec la plus grande attention le traité de 1867, Die Psychologie des Aristoteles : le recours à Aristote resterait alors nécessaire pour comprendre le projet d’une nouvelle psychologie qui n’oublie pourtant pas sa vocation métaphysique. (shrink)

This text is the introduction of the special issue “Rhythm in social interaction” edited by Chiara Bassetti and Emanuele Bottazzi in Etnografia e Ricerca Qualitativa, vol. 8, n. 3, December 2015. We thank Chiara Bassetti, Emanuele Bottazzi and the journal Etnografia e Ricerca Qualitativa for the permission to republish it. But, friend, when you grasp the number and nature of the intervals of sound, from high to low, and the boundaries of those intervals, and how many scales arise from them, (...) - Anthropologie – Nouvel article. (shrink)

Rien n’est plus faux que l’image de Dante comme génie isolé, tranchant sur son époque. Il appartient au contraire à une génération d’intellectuels italiens très caractéristique: laïes, souvent actifs dans plus d’un domaine, pratiquant abondamment l’expression poétique, engagés dans l’action politique, ces savants-citoyens partagent également une forte conscience historique. Leur inventivité se manifeste, en philosophie, en médecine et en droit, autant que dans l’expression littéraire. Outre des facteurs endogènes, une clé de ce phénomène tient à la réception active du savoir (...) naturaliste élaboré à Paris, qui est lu en Italie hors du contrôle des théologiens. Les parcours parallèles d’une douzaine de personnalité hors du commun montrent la nécessité d’élargir les cadres habituels de l’histoire intellectuelle médiévale. (shrink)

BackgroundIn recent years, there have been many studies using the Affective Neuroscience Personality Scales (ANPS) to investigate individual differences in primary emotion traits. However, in contrast to other primary emotion traits proposed by Jaak Panksepp and colleagues, there is a considerable lack of research on the LUST (L) dimension – defined as an individual’s capacity to attain sexual desire and satisfaction – a circumstance mainly caused by its exclusion from the ANPS. Therefore, this study aims to take a first step (...) toward the development of a standardized self-rate measurement for the L-disposition. For this purpose, two versions of the L-scales (L-12 and L-5) were developed and evaluated regarding reliability and aspects of validity.Materials and MethodsAfter a pilot study (N= 204; female: 81%) with an initial 20-item pool item reductions were conducted. This led to the construction of a 12-item (L-12) version and a 5-item version (L-5), which were assessed in a second sample consisting of 371 German-speaking healthy adults (58.50% female) aged 18–69 years (M= 28;SD= 9.75). Aspects of external validity were assessed by investigation of correlations with the ANPS, psychiatric symptoms (Brief Symptom Inventory-18), attachment security (Adult Attachment Scales) and personality functioning (Operationalized Psychodynamic Diagnostics Structure Questionnaire). To evaluate structural validity, both L-scales were investigated via confirmatory factor analysis (CFA).ResultsCronbach’s α indicated excellent internal consistency regarding L-12 (α = 0.90), while L-5 showed acceptable reliability (α = 0.82). CFA of a bifactor model of the L-12 indicated excellent model fit. Moreover, an excellent model fit was observed regarding a single factor model of L-5. For both scales small to moderate positive correlations were observed with SEEKING, PLAY, and secure attachment, while they exhibited small to moderate negative correlations with SADNESS, insecure attachment, lower personality functioning, and increased psychiatric symptom load.ConclusionBoth newly developed scales exhibit satisfying psychometric properties, indicating high reliability, good structural validity and plausible correlations with external criteria. Hence, this study poses an important step toward the operationalization of the LUST concept. However, more research is needed in particular with respect to the scale’s external validity and its applicability in clinical populations. (shrink)

Background Respect for human rights and bioethical principles in prisons is a crucial aspect of society and is proportional to the well-being of the general population. To date, these ethical principles have been lacking in prisons and prisoners are victims of abuse with strong repercussions on their physical and mental health. Methods A systematic review was performed, through a MESH of the following words (bioethics) AND (prison), (ethics) AND (prison), (bioethics) AND (jail), (ethics) AND (jail), (bioethics) AND (penitentiary), (ethics) AND (...) (penitentiary), (prison) AND (human rights). Inclusion and exclusion criteria were defined and after PRISMA, 17 articles were included in the systematic review. Results Of the 17 articles, most were prevalence studies (n.5) or surveys (n.4), followed by cross-sectional studies (n.3), qualitative studies (n.1), retrospective (n.1) and an explanatory sequential mixed-methods study design (n.1). In most cases, the studies associated bioethics with prisoners’ access to treatment for various pathologies such as vaccinations, tuberculosis, hepatitis, HIV, it was also found that bioethics in prisons was related to the mental health of prisoners, disability, ageing, the condition of women, the risk of suicide or with the request for end-of-life by prisoners. The results showed shortcomings in the system of maintaining bioethical principles and respect for human rights. Conclusions Prisoners, in fact, find it difficult to access care, and have an increased risk of suicide and disability. Furthermore, they are often used as improper organ donors and have constrained autonomy that also compromises their willingness to have end-of-life treatments. In conclusion, prison staff (doctors, nurses, warders, managers) must undergo continuous refresher courses to ensure compliance with ethical principles and human rights in prisons. (shrink)

Fostering research integrity (RI) increasingly focuses on normative guidance and supportive measures within institutions. To be successful, the implementation of support should be informed by stakeholders’ experiences of RI support. This study aims to explore experiences of RI support in Dutch, Spanish and Croatian universities. In total, 59 stakeholders (Netherlands n = 25, Spain n = 17, Croatia n = 17) participated in 16 focus groups in three European countries. Global themes on RI support experiences were identified by thematic analysis. (...) Themes identified were: ‘RI governance and institutional implementation’, ‘RI roles and structures’, ‘RI education and supervision’, and ‘Infrastructure, technology and tools supporting daily practice’. Experiences of support differed between countries in relation to: the efforts to translate norms into practice; the extent to which RI oversight was a responsibility of RE structures, or separate RI structures; and the availability of support close to research practice, such as training, responsible supervision, and adequate tools and infrastructure. The study reinforces the importance of a whole institutional approach to RI, embedded within local jurisdictions, rules, and practices. A whole institutional approach puts the emphasis of responsibility on institutions rather than individual researchers. When such an approach is lacking, some stakeholders look for intervention by authorities, such as funders, outside of the university. (shrink)

Early in the COVID-19 pandemic, researchers reported a surprising trend in disease outcomes: men were more likely to require hospitalization and die from COVID-19 than women. Researchers looked to sex-linked biology to explain these disparities, hypothesizing innate sex differences in immune function, suggesting the use of estrogens or androgen-suppressants as therapy, and even pushing for sex-specific vaccine strategies. Leading bioethicists like Dr. Ezekiel Emanuel at the University of Pennsylvania recently described the sex disparity in COVID-19 outcomes as "the unsolved (...) mystery" of the... (shrink)

La propuesta de Emanuele Coccia representa una vuelta a las formas más básicas y a los significados más orgá- nicos. Un golpe al antropocentrismo moderno y a la manera de construir nuestro mundo y las relaciones que tenemos con él. Un nuevo giro epis- temológico que se vuelca contra sí: a lo primero que se enfrenta es al sujeto y a su cognición universalista. No es la otredad vuelta hombre-dios, sino el mundo en y frente a nosotros, como conexiones biológicas (...) que tejen un infinito sentido de la vida orgánica. Parte del cosmos hasta regresar a él, pasa por el vientre biológico, materno, so- cial, político, simbólico y así no somos más contenedores de sentido y cono- cimiento, sino el paso de una energía universal que nunca se detiene, sólo se transforma. (shrink)

Glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide, and dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists, such as tirzepatide, have been found to be effective for treating obesity and diabetes, significantly reducing weight and the risk or predicted risk of adverse cardiovascular events. There is a global shortage of these medications that could last several years and raises questions about how limited supplies should be allocated. We propose a fair-allocation framework that enables evaluation of the ethics of current (...) practices and could guide governments, professional societies, and physicians in allocation decisions. (shrink)

The doctrine of simple individuals has its equal and opposite reaction in the view that an individual is simply a bundle of properties, that the identity of an individual is entirely dependent on the identity of its properties. This view also seems to me to be in some sense wrong and I shall attack it in passing. If all my remarks have seemed excessively polemical it is because I have been anxious to make it as clear as possible what the (...) motivation behind this paper is. I am mainly concerned with the problem concerning the "it" which underlies or has properties and I shall want to argue that the identity of an individual--what it is that makes an individual that individual--does not depend merely on its being that individual or having that piece of substratum, but it depends partially and in a complicated way on the identity of its properties. The analysis will have to exhibit the nature of that dependence. Most of the discussion will revolve around proper names and their function since it is through linguistic considerations, I think, that we get the clearest illumination. The result, in case any one is interested, will be Absolute Idealism, or something like it. (shrink)

Comprehensive in scope and research, this book will be a crucial resource for researchers in the medical sciences, as well as teachers and students alike.

1. The opinions expressed are the author's own. They do not reflect any position or policy of the National Institutes of Health, Public Health Service, Department of Health and Human Services, or any of the authors affiliated organizations.

For decades, worries about undue inducement have Pervaded clinical research, and are especially common when research is accompanied by payment or conducted in developing countries. Few ethical judgments carry as much moral opprobrium or are thought to undermine the ethical soundness of a clinical trial as thoroughly as undue inducement. Indeed, the admonition to prevent undue inducement is one of the few explicit instructions in the Common Rules requirements for informed consent.Despite their long history and pervasiveness, charges of undue inducement (...) in clinical research are almost always mistaken. Indeed, I will advance an even more radical claim: Aresearch trial that otherwise fulfills the fundamental ethical requirements for human subjects research inherently cannot create the possibility of undue inducement because substantial risk of serious harm isprecluded. Charges of undue inducement tend to express displaced and mislabeled ethical concerns about other aspects of human subjects research. Consequently, claims of undue inducement should rarely be made, and when they are advanced should be treated with skepticism, placing a heavy burden of proofon those advancing such charges. (shrink)

This book was inspired originally by the debates at the turn of the century about placebo controlled trials of antiretrovirals in HIV positive pregnant women in developing countries. Moving forward from this one limited example, the book includes several additional controversial cases of clinical research conducted in developing countries, and asks probing philosophical questions about the ethics of such trials. All clinical research by its very nature uses people to acquire generalizable knowledge to help future people. But what sorts of (...) "use" are morally permissible? What is it to exploit people? Suppose that a trial conducted in a developing country would not be ethically permissible in the developed world. Can we automatically conclude from this that the trial is unethical, that some sort of morally problematic double standard is in operation? Or might the differences in the two settings justify differences in trial design? This collection of philosophical essays examines these important questions about what exploitation is and when clinical research counts as exploitative. -/- "This is an outstanding contribution to the growing literature on the ethics of research with human subjects and a fine example of what bioethics can offer at its best. Anyone with a serious interest in these issues will need to read this book from start to finish." -Daniel Wikler, Harvard School of Public Health "This book contributes significantly to the literature on exploitation in clinical research conducted in the developing world."--Patricia Marshall, Case Western Reserve University . (shrink)

Certifications of immunity are sometimes called “immunity passports” but are better conceptualized as immunity-based licenses. Such policies raise important questions about fairness, stigma, and counterproductive incentives but could also further individual freedom and improve public health. Immunity licenses should not be evaluated against a baseline of normalcy, ie, uninfected free movement. Rather, they should be compared to the alternatives of enforcing strict public health restrictions for many months or permitting activities that could spread infection, both of which exacerbate inequalities and (...) impose serious burdens. This Viewpoint presents a framework for analyzing the ethics of immunity licenses. (shrink)

COVID-19 vaccines are likely to be scarce for years to come. Many countries, from India to the U.K., have demonstrated vaccine nationalism. What are the ethical limits to this vaccine nationalism? Neither extreme nationalism nor extreme cosmopolitanism is ethically justifiable. Instead, we propose the fair priority for residents framework, in which governments can retain COVID-19 vaccine doses for their residents only to the extent that they are needed to maintain a noncrisis level of mortality while they are implementing reasonable public (...) health interventions. Practically, a noncrisis level of mortality is that experienced during a bad influenza season, which society considers an acceptable background risk. Governments take action to limit mortality from influenza, but there is no emergency that includes severe lockdowns. This “flu-risk standard” is a nonarbitrary and generally accepted heuristic. Mortality above the flu-risk standard justifies greater governmental interventions, including retaining vaccines for a country's own citizens over global need. The precise level of vaccination needed to meet the flu-risk standard will depend upon empirical factors related to the pandemic. This links the ethical principles to the scientific data emerging from the emergency. Thus, the FPR framework recognizes that governments should prioritize procuring vaccines for their country when doing so is necessary to reduce mortality to noncrisis flu-like levels. But after that, a government is obligated to do its part to share vaccines to reduce risks of mortality for people in other countries. We consider and reject objections to the FPR framework based on a country: having developed a vaccine, raising taxes to pay for vaccine research and purchase, wanting to eliminate economic and social burdens, and being ineffective in combating COVID-19 through public health interventions. (shrink)

All investigators funded by the National Institutes of Health are now required to receive training about the ethics of clinical research. Based on a course taught by the editors at NIH, Ethical and Regulatory Aspects of Clinical Research is the first book designed to help investigators meet this new requirement. The book begins with the history of human subjects research and guidelines instituted since World War II. It then covers various stages and components of the clinical trial process: designing the (...) trial, recruiting participants, ensuring informed consent, studying special populations, and conducting international research. Concluding chapters address conflicts of interest, scientific misconduct, and challenges to the IRB system. The appendix provides sample informed consent forms. This book will be used in undergraduate courses on research ethics and in schools of medicine and public health by students who are or will be carrying out clinical research. Professionals in need of such training and bioethicists also will be interested. (shrink)

We reviewed 272 phase I oncology trial consent forms and then created an improved informed consent template in both English and Spanish by redesigning and rewording the consent form to be specific to phase I trials, to avoid repetition, and to use simplified language, identifiable sections framed by first-person questions, and tables to present information. The resulting consent form template is shorter than average and considerably easier to read . The template also meets the recommended eighth-grade maximum reading level for (...) consent forms. Use of this template should help improve the informed consent process. (shrink)

The understanding of appropriate ethical protections for participants of biomedical research has not been static. It has evolved over time, with the evolution of biomedical research as well as social values. Since World War II, there have been four major paradigms of research and research oversight operative in the United States. These paradigms incorporate different values and provide different approaches to research oversight and the protection of research participants.

What is the content of a sentence in context? A proposition, says the standard propositional view accepted in much of semantics. A set of propositions, says the hitherto little-explored view of Semantic Pluralism. The aim of this book is to motivate, develop and defend Semantic Pluralism. To achieve this aim, the book puts forward two arguments against Contextualism, the most popular propositional theory. It spells out two versions of Semantic Pluralism: Flexible Pluralism, which takes many expressions to be context-sensitive, and (...) Strong Pluralism, which denies that context-sensitivity is widespread. And it shows how Pluralists can reply to several objections that have been lodged against non-propositional semantic theories. (shrink)

The debate about justice and health care has occurred largely at a remove from the institutions it concerns; it has been about our most general moral principles, and about what things we value. This debate has foundered. But if the debate is turned in another direction, toward some moral principles that are widely accepted within those institutions, and toward principles that have to do with control over allocation decisions rather than with actually how to make those decisions, agreement may be (...) nearer at hand. (shrink)

The traditional Western understanding of life and death as a strict dichotomy is challenged by a more descriptively accurate model of life's progressive cessation. Dying can be defined by a bounded zone of residual states of life that fits better with moral intuition and more sensitively guides action toward the dying.