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)

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)

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)

In our daily lives, we continuously evaluate feedback information, update our knowledge, and adapt our behavior in order to reach desired goals. This ability to learn from feedback information, however, declines with age. Previous research has indicated that certain higher-level learning processes, such as feedback evaluation, integration of feedback information, and updating of knowledge, seem to be affected by age, and recent studies have shown how the adaption of choice behavior following feedback can differ with age. The neural mechanisms underlying (...) this age-related change in choice behavior during learning, however, remain unclear. The aim of this study is therefore to investigate the relation between learning-related neural processes and choice behavior during feedback learning in two age groups. Behavioral and fMRI data were collected, while a group of young and older adults performed a probabilistic learning task consisting of 10 blocks of 20 trials each. On each trial, the participants chose between a house and a face, after which they received visual feedback. In each block, either the house or the face image had a higher probability of yielding a reward. Participants were instructed to try to maximize their gains. Our results showed that less successful learning in older adults, as indicated by a lower learning rate, corresponded with a higher tendency to switch to the other stimulus option, and with a reduced adaptation of this switch choice behavior following positive feedback. At the neural level, activation following positive and negative feedback was found to be less distinctive in the older adults, due to a smaller feedback-evaluation response to positive feedback in this group. Furthermore, whereas young adults displayed increased levels of knowledge updating prior to adapting choice behavior, we did not find this effect in older adults. Together, our results suggest that diminished learning performance with age corresponds with diminished evaluation of positive feedback and reduced knowledge updating related to changes in choice behavior, indicating how such differences in feedback processing at the trial level in older adults might lead to reduced learning performance across trials. (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)

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)

Social innovations are urgently needed as we confront complex social problems. As these social problems feature substantial interdependencies among multiple systems and actors, developing and implementing innovative solutions involve the re-negotiating of settled institutions or the building of new ones. In this introductory article, we introduce a stylized three-cycle model highlighting the institutional nature of social innovation efforts. The model conceptualizes social innovation processes as the product of agentic, relational, and situated dynamics in three interrelated cycles that operate at the (...) micro, meso, and macro levels of analysis. The five papers included in this special issue address one or more of these cycles. We draw on these papers and the model to stimulate and offer guidance to future conversations on social innovations from an institutional theory perspective. (shrink)

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)