Personalized medicine relies on two points: 1) causal knowledge about the possible effects of X in a given statistical population; 2) assignment of the given individual to a suitable reference class. Regarding point 1, standard approaches to causal inference are generally considered to be characterized by a trade-off between how confidently one can establish causality in any given study (internal validity) and extrapolating such knowledge to specific target groups (external validity). Regarding point 2, it is uncertain which reference class leads (...) to the most reliable inferences. -/- Instead, pharmacovigilance focuses on both elements of the individual prediction at the same time, that is, the establishment of the possible causal link between a given drug and an observed adverse event, and the identification of possible subgroups, where such links may arise. We develop an epistemic framework that exploits the joint contribution of different dimensions of evidence and allows one to deal with the reference class problem not only by relying on statistical data about covariances, but also by drawing on causal knowledge. That is, the probability that a given individual will face a given side effect, will probabilistically depend on his characteristics and the plausible causal models in which such features become relevant. The evaluation of the causal models is grounded on the available evidence and theory. (shrink)

How should we make decisions when we do not know the relevant physical probabilities? In these ambiguous situations, we cannot use our knowledge to determine expected utilities or payoffs. The traditional Bayesian answer is that we should create a probability distribution using some mix of subjective intuition and objective constraints. Imprecise Bayesians argue that this approach is inadequate for modelling ambiguity. Instead, they represent doxastic states using credal sets. Generally, insofar as we are more uncertain about the physical probability of (...) an event, there is more divergence in the credal set. Hence, their approach can represent these ambiguities via the extent of the divergence. Imprecise Bayesianism has mostly been advocated for its epistemological features. In this article, we examine its properties for decision-making. We develop a model for comparing standard and Imprecise Bayesianism by testing their performances in a classic decision problem. We find that the representational tools of Imprecise Bayesianism also cause it to underperform in our tests. This issue has been overlooked, because previous research on Imprecise Bayesianism has not utilised agent-based modelling to provide information about its performance in the short-run. Overall, we reveal the Ambiguity Dilemma for Imprecise Bayesianism: To what extent should one value representational power or decision-making performance? (shrink)

Background: Evidence suggesting adverse drug reactions often emerges unsystematically and unpredictably in form of anecdotal reports, case series and survey data. Safety trials and observational studies also provide crucial information regarding the (un-)safety of drugs. Hence, integrating multiple types of pharmacovigilance evidence is key to minimising the risks of harm. Methods: In previous work, we began the development of a Bayesian framework for aggregating multiple types of evidence to assess the probability of a putative causal link between drugs and side (...) effects. This framework arose out of a philosophical analysis of the Bradford Hill Guidelines. In this article, we expand the Bayesian framework and add “evidential modulators,” which bear on the assessment of the reliability of incoming study results. The overall framework for evidence synthesis, “E-Synthesis”, is then applied to a case study. Results: Theoretically and computationally, E-Synthesis exploits coherence of partly or fully independent evidence converging towards the hypothesis of interest (or of conflicting evidence with respect to it), in order to update its posterior probability. With respect to other frameworks for evidence synthesis, our Bayesian model has the unique feature of grounding its inferential machinery on a consolidated theory of hypothesis confirmation (Bayesian epistemology), and in allowing any data from heterogeneous sources (cell-data, clinical trials, epidemiological studies), and methods (e.g., frequentist hypothesis testing, Bayesian adaptive trials, etc.) to be quantitatively integrated into the same inferential framework. Conclusions: E-Synthesis is highly flexible concerning the allowed input, while at the same time relying on a consistent computational system, that is philosophically and statistically grounded. Furthermore, by introducing evidential modulators, and thereby breaking up the different dimensions of evidence (strength, relevance, reliability), E-Synthesis allows them to be explicitly tracked in updating causal hypotheses. (shrink)

The debates between Bayesian, frequentist, and other methodologies of statistics have tended to focus on conceptual justifications, sociological arguments, or mathematical proofs of their long run properties. Both Bayesian statistics and frequentist (“classical”) statistics have strong cases on these grounds. In this article, we instead approach the debates in the “Statistics Wars” from a largely unexplored angle: simulations of different methodologies’ performance in the short to medium run. We conducted a large number of simulations using a straightforward decision problem based (...) around tossing a coin with unknown bias and then placing bets. In this simulation, we programmed four players, inspired by Bayesian statistics, frequentist statistics, Jon Williamson’s version of Objective Bayesianism, and a player who simply extrapolates from observed frequencies to general frequencies. The last player functions as a benchmark: a statistical methodology should at least outperform a crude form of induction. We focused on the performance of these methodologies in guiding the players towards good decisions. Unlike an earlier simulation study of this type, we found no systematic difference in performance between the Bayesian and frequentist players, provided the Bayesian used a flat prior and the frequentist used a low confidence level. Unlike that study, we were able to use Big Data methods to mitigate problems of random error in the simulation results. The Williamsonian player, who is a novel element of our study, also had no systematic differences in their performance, provided that they use a low confidence level. These players performed similarly even in the very short run, when players were making different decisions. Our study indicates that all three methodologies should be taken seriously by philosophers and practitioners of statistics. However, the frequentist and Williamsonian performed poorly when their confidence levels were high, and the Bayesian was surprisingly harmed by biased priors, providing some unexpected lessons for these methodologies when facing this type of decision problem. (shrink)

Calibration inductive logics are based on accepting estimates of relative frequencies, which are used to generate imprecise probabilities. In turn, these imprecise probabilities are intended to guide beliefs and decisions — a process called “calibration”. Two prominent examples are Henry E. Kyburg's system of Evidential Probability and Jon Williamson's version of Objective Bayesianism. There are many unexplored questions about these logics. How well do they perform in the short-run? Under what circumstances do they do better or worse? What is their (...) performance relative to traditional Bayesianism? -/- In this article, we develop an agent-based model of a classic binomial decision problem, including players based on variations of Evidential Probability and Objective Bayesianism. We compare the performances of these players, including against a benchmark player who uses standard Bayesian inductive logic. We find that the calibrated players can match the performance of the Bayesian player, but only with particular acceptance thresholds and decision rules. Among other points, our discussion raises some challenges for characterising “cautious” reasoning using imprecise probabilities. Thus, we demonstrate a new way of systematically comparing imprecise probability systems, and we conclude that calibration inductive logics are surprisingly promising for making decisions. (shrink)

Contemporary debates about scientific institutions and practice feature many proposed reforms. Most of these require increased efforts from scientists. But how do scientists’ incentives for effort interact? How can scientific institutions encourage scientists to invest effort in research? We explore these questions using a game-theoretic model of publication markets. We employ a base game between authors and reviewers, before assessing some of its tendencies by means of analysis and simulations. We compare how the effort expenditures of these groups interact in (...) our model under a variety of settings, such as double-blind and open review systems. We make a number of findings, including that open review can increase the effort of authors in a range of circumstances and that these effects can manifest in a policy-relevant period of time. However, we find that open review’s impact on authors’ efforts is sensitive to the strength of several other influences. (shrink)

This paper discusses the issue of overriding the right of individual consent to participation in cluster randomised trials (CRTs). We focus on CRTs testing the efficacy of non-pharmaceutical interventions. As an example, we consider school closures during the COVID-19 pandemic. In Norway, a CRT was promoted as necessary for providing the best evidence to inform pandemic management policy. However, the proposal was rejected by the Norwegian Research Ethics Committee since it would violate the requirement for individual informed consent. This sparked (...) debate about whether ethics stand in the way of evidence-based health policy, since the Norwegian Research Ethics law’s strict requirements for individual consent make it practically impossible to carry out CRTs of public health interventions. We argue that, in the case of the school closure trial, the suggested CRT would not have eliminated an epistemic gap and thus would not have justified the violation of consent rights. First, we focus on the methodological challenges to estimating quantifiable effects of school closures in the specific case of an airborne infectious disease. Second, in line with Evidential Pluralism, we highlight the value of alternative lines of evidence for informing school closure policy in a pandemic. In general, we propose that a trial requiring the waiver of participants’ consent rights must be highly likely to eliminate an epistemic gap. We elaborate on the practical aspects of this criterion and discuss the potential advantages of adding it to the Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials. (shrink)

Bentley's emendation in Horace, Ep. 1.14.9.

La fundamental idea orteguiana de que «mi vida» es «razón», difiere radicalmente de la concepción fenomenológica de la razón que alumbra Husserl en Ideen, esencialmente fundada en el ser. La razón vital es teoría del hombre, que es su proyecto circunstancial; su estímulo argumental procede de una reflexión estética sobre todo orientada a la comprensión del realismo y del idealismo artísticos, y cuyas consecuencias filosóficas serán decisivas.

La experiencia de la pobreza llama a la economía a humanizarse y a la filosofía a pensar etimológicamente desde las “normas de la casa”. Se descubre, entonces, el sentido de las épocas y de las generaciones filosóficas, la razón de su fecundidad y de su pobreza, así como la relación entre estas y la justicia.

. This article analyses some of the anatomical waxes in the Museo della Specola in Florence. Executed in at least two different periods in the history of Florentine wax modelling, they project culturally determined images of the body which are analysed from a historico-semiotic perspective. “Rotten corpses,” a “disembowelled woman” and a “flayed man” emerge as salient figures in the collection and reveal the close tie between anatomical representations and aesthetics, social relations and religious scruples, in other words, the culture (...) tout court which produced them. (shrink)

The right to ‘domestic remedies’, which ideally connects ‘subsidiarity’ and ‘embeddedness’ of the ECHR in the legal systems of member States, is deemed to play a crucial role for the Strasbourg machinery survival as well as for an effective protection of human rights, especially in the field of the ‘reasonable-time’ requirement. In this respect the Italian case seems an excellent test. Once a compensatory remedy was introduced in the Italian legal system by Law No. 80 of 2001 (the ‘Pinto Act’), (...) it soon appeared that such a remedy could be considered ‘effective’ in so far as it was implemented in accordance with the ECtHR’s jurisprudence. Therefore a legal tool for the interaction between ECtHR and Italian courts had to be found. Nevertheless, the results of this interaction might suggest that the domestic remedy has neither increased the protection of the reasonable-time requirement in Italy nor is it the final solution to the ECtHR’s overload. (shrink)

BackgroundPositive psychosocial factors can play an important role in the development of cardiovascular disease. Among them, psychological resilience is defined as the capacity of responding positively to stressful events. Our aim was to assess whether PR is associated with CVD or metabolic disturbances through a systematic review.MethodsWe gathered articles from PubMed, Web of Science, PsycInfo, and Google Scholar up to October 28, 2021. We included articles that were in English, were observational, and had PR examined as exposure. The CVD outcomes (...) were either clinical or metabolic outcomes.ResultsOur literature search identified 3,800 studies, of which 17 met the inclusion criteria. Of them, seven were longitudinal and 10 cross-sectional, and 13 were on adults and four on children. The exposure assessment was heterogeneous, i.e., 12 studies used different kinds of self-administered questionnaires and five used interviews with a psychologist. Regarding outcomes, five studies investigated CVD, seven obesity, one metabolic syndrome, two hypertension, four dyslipidemia, and four diabetes. In longitudinal studies, PR was found to have an inverse association with included outcomes in five studies from the Swedish military conscription cohort but had no association with CVD in a study on African-American women and was associated with slower progression of diabetes in a general population. The cross-sectional studies showed that the prevalence of disease was not associated with PR in many cases but the progression of disease was associated with PR.ConclusionPR seems to have a possibly favorable association with CVD and metabolic disturbances that differs according to the type of outcome and population. Our study limitations are given by the small number of studies available and the heterogeneity in PR measurement.Systematic Review Registration[https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=237109], identifier [CRD42021237109]. (shrink)

The meaning of justice can be defined according to a juridical, human, theological, ethical, biomedical, or social perspective. It should guarantee the protection of life and health, personal, civil, political, economic, and religious rights, as well as non-discrimination, inclusion, protection, and access to care. In this review, we deal with three theoretical concepts that define justice in all its aspects. (1) The utilitarian theory, which justifies moral statements on the basis of the evaluation of the consequences that an action produces, (...) elaborating a pragmatic model of medical science. (2) The libertarian theory, which considers freedom as the highest political aim, thus absolutizing the rights of the individual; here, the principle of self-determination, with respect to which the principle of permission/consent is the fundamental presupposition, plays a central role in the definition of the person. (3) The iusnaturalist theory, in which man’s moral freedom is identified with the ability to act by choosing what the intellect indicates to him as good; the natural moral law that drives every conscience to do good is therefore realized in respect for the person in the fullness of his rights. In conclusion, different forms and conceptions of justice correspond to different organizations of society and different ways of addressing ethical issues in the biomedical domain. (shrink)

A pesar de los matices y variaciones de significado, el concepto husserliano de intencionalidad no deja de estar al servicio de la idea clásica de la verdad como adaequatio, finalmente adaptada al orden monádico de la conciencia trascendental. Veremos, sin embargo, que en los análisis de Husserl sobre la conciencia interna del tiempo se manifiesta toda la dificultad para interpretar intencionalmente la esfera pasiva de la conciencia, peligrando la peculiar vocación a la verdad de la misma intencionalidad. Intentaremos, mediante las (...) últimas ideas husserlianas sobre la constitución eidética, encontrar una génesis pasiva del sentido ideal intencional sin perder su referencia egológica. Abstract: Despite the nuances and differences of meaning, the husserlian’s concept of intentionality supplies coherently that of classic true as adaequatio, even if adapted to the monadic order of transcendental conscience. We will show how Husserl’s analysis of inner time consciousness shows all the difficulties for an intentional interpretation of the passive sphere of consciousness, altering the peculiar vocation of intentionality to truth. Through the latest husserlian ideas on constitution, we will try to find a passive genesis to the ideal meaning of intentionality without losing its egologic reference. -/- . (shrink)

Né vers 1600 en Italie, l'opéra encourait les foudres de Marcello dès 1720. L'ouverture des salles au public, les nécessités commerciales et le vedettariat l'avaient éloigné des idéaux qui présidèrent à sa naissance. L'opuscule de Benedetto Marcello aborde, sur le ton de la dérision et de la satire, tous les aspects de l'opéra, du livret à la musique, en passant par les chanteurs, les compositeurs, les directeurs de théâtre, la mise en scène, etc. Le texte méritait une nouvelle traduction française (...) (la dernière datait de la fin du dix-neuvième siècle), plus précise et plus complète, car le savant compositeur de l'Estro poetico-armonico y déploie une verve irrésistible, proche de celle dont se servira Carlo Goldoni dans l'imprésario de Smyrne. Cette satire représente l'étincelle qui allait embraser le flambeau de la réforme par le biais du comte Francesco Algarotti (1712-1764) poète et écrivain. Son Essai sur l'Opéra en musique contient en effet tous les points importants sur lesquels Calzabigi et Gluck allaient asseoir leur reconstruction : choix du livret, rôle de la poésie et de la musique, rôle des chanteurs, du compositeur, moyens et contrôle artistiques des productions. La traduction française qu'un fit Chastellux en 1773, nonobstant sa finesse et son élégance, fait pourtant figure de " belle infidèle ". Force nous était donc d'élaborer là encore une nouvelle traduction de ce texte fondateur. A côté de ces deux grands titres, nous avons réuni un dossier important d'écrits émanant des acteurs de la réforme : Métastase, Angiolini, Calzabigi, Gluck et Du Roullet. (shrink)

En approfondissant la pensée d'Ortega, nous découvrons que la métaphysique est une science de la réalité radicale, du sens et un mode de vie. Nous verrons que la réalité radicale est la vie individuelle et que le sens de la raison vitale est personnel, ce qui implique un changement dans la conception traditionnelle du sujet, de l'objet et de la vérité.

Two quantum Macro-states and their Macroscopic Quantum Superpositions (MQS) localized in two far apart, space-like separated sites can be non-locally correlated by any entangled couple of single-particles having interacted in the past. This novel “Macro-Macro” paradigm is investigated on the basis of a recent study on an entangled Micro-Macro system involving N≈105 particles. Crucial experimental issues as the violation of Bell’s inequalities by the Macro-Macro system are considered.

In this paper we analyze the resilience to decoherence of the Macroscopic Quantum Superpositions (MQS) generated by optimal phase-covariant quantum cloning according to two coherence criteria, both based on the concept of Bures distance in Hilbert spaces. We show that all MQS generated by this system are characterized by a high resilience to decoherence processes. This analysis is supported by the results of recent MQS experiments of N=3.5×104 particles.

For a better understanding of Julián Marías’ Metaphysic Antropology, it is recommendable going back to the Ortega’s mereology, epistemology and metaphysic, especially in order to clarify the meaning of “structure”, “system”, “organ” and “function”. The vital reason is personal project as the systematic openness to its circumstance, whose unitary, empirical and structural structure is “man”.

In lieu of an abstract, here is a brief excerpt of the content:“It’s not true, but I believe it”: Discussions on jettatura in Naples between the End of the Eighteenth and Beginning of the Nineteenth CenturiesFrancesco Paolo de CegliaIntroduction: What is Jettatura?Non èvero...ma ci credo (“It’s not true... but I believe it”) is the title of a comedy by the Italian actor and playwright, Peppino De Filippo, younger brother of the more famous Eduardo, which was staged for the first time (...) in 1942. The narrated events take place in the twentieth century and concern Gervasio Savastano, a Neapolitan businessman who is tormented by the fear of jettatura. The character, victim of grotesque events, first sacks a worker, believing him to be a jettatore, and then hires another, who is a hunchback and so should bring him good luck. In the end, however, it is discovered that the presumed jettatore has never harmed anyone and that the hunchback is not what he seems: he has stuffed his jacket in order to enter into the good graces of the gullible businessman and marry his daughter, with whom he has planned a con trick. The “lucky” events ascribed to his presence can therefore be considered casual. The epilogue? In keeping with the logic of compromise, typical of the brothers De Filippo’s theater, even though the character is rationally convinced of the unfounded nature of his beliefs, he remains adamant: “It’s not true, but I believe it” in other words.1 [End Page 75]“Where I come from, jettatura rules,” wrote the journalist and scriptwriter Giuseppe Marotta in 1947. Indeed, it is still a part of popular Neapolitan culture today.2 Often confused with similar beliefs, such as fascination (fascino) and the evil eye (malocchio), jettatura assumed its present form between the end of the eighteenth and beginning of the nineteenth century, at a time when a polite debate on its nature was taking shape in the city. In this period, the epistemological pluralism animating the discussions was translated into a variety of interpretative hypotheses and literary genres, in which grotesque atmospheres and spirited quips also found room, all perfectly in line with what could be considered the Weltanschauung of Savastano. It is the purpose of this article to examine these discussions, which even spread the term abroad and, with it, the “local color” of the concept.Nineteenth-century European writers on jettatura knew the Neapolitan authors well, and either quoted them explicitly or associated them with characters whose names were a deformation of real people’s: for example, Volitta for Valletta (Stendhal), don Jo (Stendhal) or Ojori (Dumas) for De Jorio. They explained that jettatura corresponded to the more familiar evil eye, but they left the term in Italian, as if to underline the fact that it was untranslatable.Is jettatura a mere anthropological issue, linked to a “primitive” culture, in the face of which official science would remain refractory? A belief that could not be exported or shared by those educated in more “highly developed” contexts? Well, in part, yes. Nevertheless, in the 1840s there was a visitor to Naples who expressed himself in the following terms: “When a foreigner arrives in Naples, at first he laughs at jettatura, then, little by little, he becomes troubled by it, and finally, after a stay of three months, you will see him covered in horns and with his right hand forever clenched [to ward off evil].”3 [End Page 76]So wrote the novelist Alexandre Dumas, père, one of the many travellers who, after having completed the Grand Tour of southern Italy, decided to describe its picturesque scenes and backward customs.4 Creating a veritable topos of travel literature, in the same period the philologist Karl August Mayer commented, “often foreigners let themselves be influenced” by local “superstitions.”5 Indeed many of them were captivated by these Neapolitan beliefs, despite their desire to remain objective and detached; and so they were “converted,” and driven to seek scientific explanations, often after meeting “a Real Jettatore,” whose image had nothing in common with the exotic fantasies of “a French Novelist’s Idea of Jettatore.”6Actually, Dumas and Mayer probably exaggerated somewhat in order to make their descriptions more... (shrink)

«Hermeneutic» means interpretation, that is, looking from a point of view. In this study we try to interpret from the vital reason, the method of Ortega y Gasset, his and his disciple Julián Marías, the Aristotelian concept of «substance». If life is the radical reality, as Ortega stresses, and the person its programmatic realization, in Marías’ opinion, a vital reason of the concept of οὐσία, means to discover its capacity to understand human life. We will find, as a matter of (...) fact, that there are four limits, essentially, that distance the philosopher from that comprehension. By them, we will find the core of the greatest contradictions of the Aristotelian thought, that has been subject to intense critics throughout its history. We will concern, especially, on the function of language in the Greek conception of reason, on the interpretations that brought to «being» and «entity» as Aristotle’s thought starting point «Hermenéutica» significa interpretar, mirar desde un punto de vista. En este estudio buscamos interpretar desde la «razón vital», el método de Ortega y Gasset y su discípulo Julián Marías, el concepto aristotélico de «sustancia». Si la vida es la realidad radical, como afirma Ortega, y la persona es su realización programática, según entiende Marías, una razón vital de la οὐσία significa descubrir su capacidad de comprensión para con la vida humana. Encontraremos, entonces, que hay esencialmente cuatro límites que desvían de esa comprensión; mediante ellos, habremos encontrado el núcleo de importantes contradicciones del pensamiento aristotélico que han sido objeto de encendidos debates a lo largo de la historia. Nos centraremos, sobre todo, en la función del lenguaje en la concepción de la razón griega, en los supuestos interpretativos del «ser» y del «ente» como puntos de partida del pensamiento de Aristóteles . (shrink)

What is life, and where does it come from? The question is very old, but it reemerged in the seventeenth century with the crisis of the Aristotelian-Galenic paradigm. Matter was now stripped of any impulse and capacity for self-organization; therefore, it was necessary to find something that would take into account the strength and information that it seemed to hold, especially in what were considered vital phenomena. Georg Ernst Stahl and Friedrich Hoffmann, both professors in Halle and responsible for two (...) of the most famous medical systems of the first half of the eighteenth century, offered solutions to the problem that only appear to be very different. The first invoked the soul as an ideal place of production of the energy that allowed the human body to fight the putrefactive forces in the natural world; the second referred to the concept of ether, to which he attributed modes of action basically similar to those that tradition attributed to vegetative and sensitive souls. This paper highlights the positions of the two physicians, setting them in the climate of the revisitation of ancient certainties that characterized natural philosophy in the seventeenth and eighteenth centuries. (shrink)

. The subject of this paper is Georg Ernst Stahl's reflections on epilepsy. In the German physician's work, the concept of disease is stratified: it is the morbid idea which causes dysfunctions in the animal economy, as well as irregular motion, overabundance and ultimately an alteration of the corporeal humours. In particular, epilepsy is an affection deriving from an altered functioning of the bodily motions, caused by abnormal blood flow, intestinal worms, anatomical defects, foreign bodies, and the passions of the (...) soul. While a certain medical tradition attributed a nervous origin to epilepsy, Stahl, giving it a humoural genesis, openly shows the theoretical premises on which his physiology rests. So, Stahlian physiology appears to be a non-mechanistic, teleological-inspired, hydraulicism. (shrink)