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Objective To describe demographic, clinical and laboratory features of systemic sclerosis sine scleroderma (ssSSc) in a large multicentre systemic sclerosis (SSc) cohort. Methods Data involving 1808 SSc patients from Italian Systemic sclerosis PRogression INvestiGation registry were collected. The ssSSc was defined by the absence of any cutaneous sclerosis and/or puffy fingers. Clinical and serological features of ssSSc were compared with limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) subsets. Results Among patients with SSc, only 61 (3.4%) were classified as having ssSSc (F/M=19/1). Time from Raynaud's phenomenon (RP) onset to diagnosis was longer in ssSSc (3 years, IQR 1-16.5) than lcSSc (2 years, IQR 0-7), and dcSSc (1 year, IQR 0-3) (p<0.001). Clinical ssSSc phenotype was comparable to lcSSc, except for digital pitting scars (DPS) (19.7% vs 42%, p=0.01), but significantly milder than dcSSc, particularly for digital ulcers (DU) (6.6% vs 35.7%, p<0.001), oesophagus (46.2% vs 63.5%, p=0.009), lung (mean diffusion capacity for carbon monoxide 72.2±19.6 vs 62.4±22.8, p=0.009; mean forced vital capacity 105.6±21.7 vs 89.2±20.9, p<0.001) and major videocapillaroscopic alterations (late pattern 8.6% vs 47.6%, p<0.001). Moreover, in ssSSc the percentages of anticentromere and antitopoisomerase were comparable to lcSSc (40% and 18.3% vs 36.7% and 26.6%), but divergent respect to dcSSc (8.6% and 67.4%, p<0.001). Conclusion The ssSSc is a quite rare disease variant characterised by clinico-serological features comparable to lcSSc, but significantly different from dcSSc. Overall, longer RP duration, low percentages of DPS and peripheral microvascular abnormalities, and increased anti-centromere seropositivity distinguish ssSSc. Further investigations based on national registries might provide useful insights on the actual relevance of the ssSSc within the scleroderma spectrum.

Introduction Nintedanib (NTD) has been shown to be effective in systemic sclerosis (SSc)-interstitial lung disease (ILD). Here we describe the efficacy and safety of NTD in a real-life setting. Methods Patients with SSc-ILD treated with NTD were retrospectively evaluated at 12 months prior to NTD introduction; at baseline and at 12 months after NTD introduction. The following parameters were recorded: SSc clinical features, NTD tolerability, pulmonary function tests and modified Rodnan skin score (mRSS). Results 90 patients with SSc-ILD (65% female, mean age 57.6±13.4 years, mean disease duration 8.8±7.6 years) were identified. The majority were positive for anti-topoisomerase I (75%) and 77 (85%) patients were on immunosuppressants. A significant decline in %predicted forced vital capacity (%pFVC) in the 12 months prior to NTD introduction was observed in 60%. At 12 months after NTD introduction, follow-up data were available for 40 (44%) patients and they showed a stabilisation in %pFVC (64±14 to 62±19, p=0.416). The percentage of patients with significant lung progression at 12 months was significantly lower compared with the previous 12 months (60% vs 17.5%, p=0.007). No significant mRSS change was observed. Gastrointestinal (GI) side effects were recorded in 35 (39%) patients. After a mean time of 3.6±3.1 months, NTD was maintained after dose adjustment in 23 (25%) patients. In nine (10%) patients, NTD was stopped after a median time of 4.5 (1-6) months. During the follow-up, four patients died. Conclusions In a real-life clinical scenario, NTD, in combination with immunosuppressants, may stabilise lung function. GI side effects are frequent and NTD dose adjustment may be necessary to retain the drug in patients with SSc-ILD.

BACKGROUND: Scarce data are available regarding rebleeding predictors in poor-grade aneurysmal subarachnoid hemorrhage (aSAH). OBJECTIVES: To investigate predictors and clinical impact of rebleeding in a national multicentric poor-grade aSAH. METHODS: Retrospective analysis of prospectively collected data from the multicentric Poor Grade Aneurysmal Subarachnoid Hemorrhage Study Group (POGASH) registry of consecutive patients treated from January 1, 2015, to June 30th, 2021. Grading was defined as pretreatment World Federation of Neurological Surgeons grading scale IV-V. Ultra-early vasospasm (UEV) was defined as luminal narrowing of intracranial arteries not due to intrinsic disease. Rebleeding was defined as clinical deterioration with evidence of increased hemorrhage on subsequent computed tomography scans, fresh blood from the external ventricular drain, or deterioration before neuroradiological evaluation. Outcome was assessed by the modified Rankin Scale. RESULTS: Among 443 consecutive World Federation of Neurological Surgeons grades IV-V patients with aSAH treated within a median of 5 (IQR 4-9) hours since onset, rebleeding occurred in 78 (17.6%). UEV (adjusted odds ratio [OR] 6.8, 95% CI 3.2-14.4; P <.001) and presence of dissecting aneurysm (adjusted OR 3.5, 95% CI 1.3-9.3; P =.011) independently predicted rebleeding while history of hypertension (adjusted OR 0.4, 95% CI 0.2-0.8; P =.011) independently reduced its chances. 143 (32.3) patients died during hospitalization. Rebleeding emerged, among others, as an independent predictor of intrahospital mortality (adjusted OR 2.2, 95% CI 1.2-4.1; P =.009). CONCLUSION: UEV and presence of dissecting aneurysms are the strongest predictors of aneurysmal rebleeding. Their presence should be carefully evaluated in the acute management of poor-grade aSAH.

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Enhanced Recovery After Surgery (ERAS) pathway is a multi-di-sciplinary, patient-centered protocol relying on the implementation of the best evidence-based perioperative practice. In the field of colorectal surgery, the application of ERAS programs is associated with up to 50% reduction of morbidity rates and up to 2.5 days reduction of postoperative hospital stay. However, widespread adoption of ERAS pathways is still yet to come, mainly because of the lack of proper information and communication. Purpose of this paper is to support the diffusion of ERAS pathways through a critical review of the existing evidence by members of the two national societies dealing with ERAS pathways in Italy, the PeriOperative Italian Society (POIS) and the Associazione Italiana Chirurghi Ospedalieri (ACOI), showing the results of a consensus development conference held at Matera, Italy, during the national ACOI Congress on June 10, 2019.

It is argued that attempts to derive policy prescriptions from current models of perfectly competitive economies overvalues unjustifiably their power and ignores their limits. Impersonality and anonymity often are inconsistent with Pareto efficiency if agents behave rationally, at least at the individual level. Personalised, potentially durable relationships together with societies, endowed with appropriate social rules can reach cooperative solutions that can be supported as non-cooperative Nash equilibriums. The effects expected from the recent drive to structural reforms are therefore very doubtful. Si argomenta che i tentativi di derivare indicazioni di politica economica dai modelli usuali di economie di perfetta concorrenza sovrastimano le loro capacità e ignorano i loro limiti. Impersonalità e anonimità sono spesso incompatibili con l’efficienza paretiana se gli agenti si comportano in maniera individualmente razionale. Relazioni personalizzate potenzialmente durature e società dotate di un appropriato insieme di regole sociali possono raggiungere soluzioni cooperative come equilibri di Nash, non cooperativi. Le speranze riposte nella re-cente spinta verso le riforme strutturali possono perciò rivelarsi infondate.

Most of current economic models center on markets, possibly perfectly competitive, and the price mechanism as coordinating devices of individual decisions. Casual observation suggests that most of this task is actually carried out by personalized relationships and long term commitments that allow cooperation to be supported as a Nash, non-cooperative equilibrium in appropriate conditions. They work as a substitute absent future markets and as risk sharing devices. Some applications to the study of labor markets and firms are outlined. Gran parte dei modelli teorici correnti si focalizzano sui mercati, possibilmente di concorrenza perfetta, ed il meccanismo dei prezzi come strumenti di coordinamento delle decisioni individuali. Anche una superficiale osservazione della realtà suggerisce che in questo hanno un ruolo molto importante le relazioni personalizzate e gli impegni a lungo termine che, appropriatamente disegnati, permettono di raggiungere cooperazione come equilibrio non cooperativo di Nash. Esse funzionano da sostituto di mercati futuri assenti e di condivisione del rischio. Alcune applicazioni allo studio del mercato del lavoro e all’analisi dell’impresa sono sommariamente tratteggiate.

Partendo dai giochi tra due agenti per poi passare al caso di n si forniscono gli elementi essenziali per caratterizzare i problemi posti dalla proprietà comune soprattutto in termini di efficienza dell’uso del bene che ne è oggetto. Si discutono inoltre le condizioni in cui questa forma di detenzione è ottimale ed i problemi di incentivazione alla loro produzione.

Starting with a prisoner’s dilemma, a simple taxonomy of the possible characteristics of a game is introduced. This forms the basis for discussing repeated interactions and the emergence of personalised rules used in durable relationships. When by their nature, interactions are sporadic, much of the same results can be obtained by the use of social rules. Finally, the use of formal contracts, typically incomplete, and a third party to solve conflicts is outlined. The Appendix contains a summary introduction to the problem of incompleteness of norm systems.

Starting with a prisoner’s dilemma, a simple taxonomy of the possible characteristics of a game is introduced. This forms the basis for discussing repeated interactions and the emergence of personalised rules used in durable relationships. When by their nature, interactions are sporadic, much of the same results can be obtained by the use of social rules. Finally, the use of formal contracts, typically incomplete, and a third party to solve conflicts is outlined. The Appendix contains a summary introduction to the problem of incompleteness of norm systems.

Starting with a prisoner’s dilemma, a simple taxonomy of the possible characteristics of a game is introduced. This forms the basis for discussing repeated interactions and the emergence of personalised rules used in durable relationships. When by their nature, interactions are sporadic, much of the same results can be obtained by the use of social rules. Finally, the use of formal contracts, typically incomplete, and a third party to solve conflicts is outlined. The Appendix contains a summary introduction to the problem of incompleteness of norm systems.

Players have consonant interests if each has a strategy favourable to the pursuit of his own and the interests of the others when the latter adopt a best response. Reasonableness is to move according to such a strategy at the stage reached, reaping the gains this generates. Some overt games hide an underlying game in the choice of rules of choice in which reasonableness is substantively rational, credible and leads to a state that Pareto dominates the Nash equilibria of the original game. The paper contains an application to the finite prisoner’s dilemma

The essay explores - through an original approach that intertwines theoretical and historical analysis, with a style similar to many works of Alberto Quadrio Curzio – the complex relations institutions and the functioning of economic systems. In doing so, the author dwells on income distribution in economic systems where, of their size (and of consequent increase of complexity the economic interactions that exist within them), the separation between consumption and production decisions has become radical. The considers the development/underdevelopment dilemma as a possible consequence of a strained acceleration in economic and technological changes of economic systems to which institutions have not adjusted, and of the relevance, in national income, of exploiting non-produced natural resources. A temporal separation of production and consumption decisions, that is separating decisions for saving from investment and how economic equilibrium can be modified with the introduction money, is considered in the last section of the paper. The relation of the latter with mining and the transformation of precious metal, first of all gold, already extensively examined by Alberto Quadrio Curzio since the beginning of the 1980s, is also discussed

After a summary review of binary relations and their properties, it presents the main axioms used in the theory of choice. The several formulation of completeness and transitivity are used to outline their implications for discussing freedom and collective choice problems. After a chapter on revealed preference, the assumption of continuity is introduced and the main results on the representation of preferences. The following chapter discusses the axiom of rationality and its interpretations. The book ends with an introduction to the theory of choice under uncertainty.

Starting from a discussion of the simple Robinson economy, it gives an introduction to the basic tools of analysis for an economic system and the different approaches one can take. After discussing the main problems to be faced in going from the one agent to the multi agent case, it presents the theory of the consumer and that of the firm. The main results derived in these chapter are then use to give an outline of general equilibrium and welfare economics.

The paper tries to show how basically similar institutional settings produce very different results in different conditions, how institutions evolved to solve new problems and exploit new possibilities as the economic setting changed in time, the problems these innovations raised and the different ways one tried for solving them. Simple adoption of the institutions which characterize advanced economies is unlikely to be a sound path for developing economies coming from very different histories.

The concept of a repeated game is introduced and applied to the case of the centipede, the finite and the indefinitely repeated prisoner’s dilemma. The consequences of the assumption of common knowledge of rationality are outlined. A concept of reasonableness is introduced and some of its effects are discussed.

It gives an informal definition of the main elements of a game: the set of players, the concept of a move and of a strategy, the normal and the extended form, a first introduction to the description of information, the set of results that can be reached and the value each player attaches to a result.

After introducing the binary relation of domination and its properties, one defines the concept of non dominated strategies and some conditions for their existence, the concept of solution of a game, that of rationalizability, that of best reply and the concept of non cooperative Nash equilibrium

After a summary introduction to the concept of a game, it presents some of the examples more often used in the literature (head and tail, peaches and bees, traffic light, prisoner’s dilemma, battle of the sexes and stag hunt games) with a brief discussion of the different situations and problems they portray.

A simple proof of existence of a non cooperative Nash equilibrium is briefly discussed, together with an introduction to the problems arising from its uniqueness or non uniqueness, to the properties which can be ascribed to an equilibrium and those connected with the search for an equilibrium.

Nelle discussioni sul come gestire il dopoguerra, le possibili radici economiche del secondo conflitto, l’esistenza di contrasti di interesse e della lotta per la conquista di mercati con strumenti sfortunatamente diversi da quelli economici, hanno quasi certamente avuto un ruolo importante. L’impressione è che si sia pensato di creare condizioni che evitassero il ripresentarsi degli stessi fenomeni attraverso la spinta all’apertura dei mercati e l’adozione del libero scambio, seguendo peraltro la visione prevalente nell’ambito della teoria del commercio internazionale, forse senza dare adeguato peso al fatto che avevano la loro origine nelle caratteristiche degli assetti produttivi industriali dei vari paesi, nella struttura degli incentivi che questi generavano e inducevano a controllare e “promuovere” gli scambi.

Dalla seconda metà degli anni ’70 e soprattutto negli anni ’80, l’Europa è interessata da due fenomeni strettamente interrelati. Da un lato, si estende il processo di apertura dei mercati interni dei paesi CEE, con una tappa fondamentale costituita dall’adozione dell’Atto Unico. D’altro lato, in molti di questi paesi emergono sempre più prepotentemente i problemi associati al modello “cooperativo” nelle varie declinazioni nazionali.

Making use of and following substantive rationality is a costly and not always feasible option. In games, this option generates two levels of reasoning. The player has to decide how to play the overt game, but this requires him to decide how to play an underlying game in which the alternatives are to follow either substantive rationality or a different rule, here that of reasonableness, in playing the overt game. A strategy is reasonable if coupled with its best response it results in the player that adopts it achieving the highest payoff among those dominating the Nash equilibria of the overt game. The underlying game can have more than one equilibrium. Substantive rationality in the underlying game can justify behaviour which is at odds with substantively rational behaviour in the overt game. The case of the centipede is used as an example. Key words: Common knowledge, Rationality, Backward induction, Reasonableness, Incomplete information, Centipede game.

Nelle discussioni sul come gestire il dopoguerra, le possibili radici economiche del secondo conflitto, l’esistenza di contrasti di interesse e della lotta per la conquista di mercati con strumenti sfortunatamente diversi da quelli economici, hanno quasi certamente avuto un ruolo importante. L’impressione è che si sia pensato di creare condizioni che evitassero il ripresentarsi degli stessi fenomeni attraverso la spinta all’apertura dei mercati e l’adozione del libero scambio, seguendo peraltro la visione prevalente nell’ambito della teoria del commercio internazionale, forse senza dare adeguato peso al fatto che avevano la loro origine nelle caratteristiche degli assetti produttivi industriali dei vari paesi, nella struttura degli incentivi che questi generavano e inducevano a controllare e “promuovere” gli scambi

Appena si abbandona il mondo di Robinson e si ammette l’esistenza di due centri decisionali, dotati ognuno di obiettivi propri potenzialmente in conflitto con quelli dell’altro e di informazione privata, i problemi di base sono quelli dell’individuazione di ciò che regola, da un lato, la definizione ed il contenuto delle sfere di autonomia di ciascuno e, d’altro lato, le loro interazioni. Nel primo campo si usano solitamente la forza e la capacità di coazione che l’uno può esercitare sull’altro, nel secondo ci si concentra sulla possibilità che attraverso accordi “volontariamente” stipulati ci si possa coordinare su comportamenti che consentono ad entrambi di raggiungere livelli di realizzazione degli obiettivi individuali più alti di quelli raggiungibili in loro assenza.

Il problema principale affrontato già durante e subito dopo il termine del secondo conflitto è quello della costruzione di istituzioni che regolino, nella fase post-bellica, gli equilibri tra i paesi, in particolare quelli economici e con attenzione quasi esclusivamente concentrata su quelli industrializzati.

Far parte di una determinata cultura e società richiede di possedere il linguaggio che consente di mandare segnali e di leggere quelli che gli altri inviano, di saperli selezionare, soprattutto di far parte di reti e di comunità, e perciò di essere parte di relazioni personalizzate potenzialmente durature e di comunità che si caratterizzano per l’adozione di procedure di inclusione ed esclusione e di un insieme di regole sociali, comunità che si vincolano sia a rispettarle, sia a richiederne il rispetto. Collettività formate da individui appartenenti alla medesima cultura sono caratterizzate dalla possibilità di sostenere un grado di cooperazione,e quindi di realizzare guadagni di efficienza altrimenti impossibili da raggiungere, almeno in generale, quando una parte delle interazioni assume la forma di gioco.

Per cominciare con situazioni molto semplici,si supponga che vi siano solo due agenti. Nella tradizione Hobbesiana, si può ritenere che sia la forza a determinare quanto ciascuno può affermare e difendere la propria autonomia e vincolare quella altrui, o, viceversa,essere costretto ad accettare vincoli alla propria. Tipicamente questa visione viene applicata a condizioni di vita relativamente primitive.

Nel processo di trasformazione dall’assetto feudale a quello moderno, i conflitti tra stati mettono in evidenza l’importanza degli incentivi a fare, ad usare nella maniera più efficiente le risorse di cui un paese dispone. Ma questi incentivi operano essenzialmente a livello individuale o di unità famigliari ed introdurli porta ad un ampliamento della sfera di autonomia riconosciuta e attribuita al singolo, su cui gli viene riconosciuto potere ma anche responsabilità di decisione.

Nei modelli di economia internazionale, esistono i paesi ma non esiste una spiegazione per la loro esistenza e persistenza. Del resto, in gran parte della teoria economica corrente esistono agenti ma manca un processo che spieghi la loro formazione; come i paesi, essi vengono presi come dati esogenamente. Ma per i paesi, il problema è aggravato dal fatto che si lascia ancor più indeterminato cosa essi siano e cosa essi possano fare. Nel caso degli agenti, cosa determina il contenuto delle sfere di autonomia individuale e garantisce il loro rispetto è lasciato largamente inspiegato ma, in genere, viene specificato: ciascuno di essi parte con una dotazione individuale e si suppone che intraprenda poi interazioni con gli altri solo su base volontaria

Il nostro contributo cerca di collocare il dibattito sui livelli di governo e la costituzione economica europea nel quadro di un’analisi delle conseguenze, potenziali o già effettive, del processo di progressiva, ma ancora molto meno che completa, integrazione dei mercati dei beni e dei fattori di produzione. La discussione si innesta in un quadro di riferimento teorico che cerca di estendere l’impostazione tradizionale considerando i risultati della teoria più recente, soprattutto in tema di incertezza causata dall’incompletezza dei mercati, distribuzione asimmetrica dell’informazione, uso dei contratti come meccanismi di coordinamento, relazioni ripetute e meccanismi di costruzione della reputazione. Tutti questi filoni della teoria più recente mettono in luce i limiti che il paradigma di concorrenza perfetta manifesta se viene usato quale chiave interpretativa dei fenomeni economici reali. In particolare, l’abbandono del paradigma di concorrenza perfetta da un lato evidenzia i contesti nei quali l’intervento pubblico risulta auspicabile, sia per incrementare l’efficienza stimolando l’impiego della capacità produttiva del sistema, sia a scopi redistributivi; dall’altro rende meno chiari i benefici normalmente attribuiti all’apertura ed integrazione dei mercati, sottolineando soprattutto la possibilità che ci siano effetti asimmetrici nella remunerazione dei fattori di produzione e dunque che siano necessari interventi di politica per garantire il consenso sociale all’integrazione medesima. Se dunque le necessità di governo dell’economia, già presenti in un contesto di relativa non integrazione, si fanno più pressanti con il procedere dell’integrazione, il problema della attribuzione delle competenze ai livelli di governo diventa centrale. Distinguiamo, sperando di non semplificare troppo, due grandi categorie di intervento pubblico: le politiche per l’efficienza (politiche della domanda aggregata e industriali) e quelle redistributive (dirette o indirette)

BackgroundAlthough left-right asymmetries are common features of nervous systems, their developmental bases are largely unknown. In the zebrafish epithalamus, dorsal habenular neurons adopt medial (dHbm) and lateral (dHbl) subnuclear character at very different frequencies on the left and right sides. The left-sided parapineal promotes the elaboration of dHbl character in the left habenula, albeit by an unknown mechanism. Likewise, the genetic pathways acting within habenular neurons to control their asymmetric differentiated character are unknown.ResultsIn a forward genetic screen for mutations that result in loss of habenular asymmetry, we identified two mutant alleles of tcf7l2, a gene that encodes a transcriptional regulator of Wnt signaling. In tcf7l2 mutants, most neurons on both sides differentiate with dHbl identity. Consequently, the habenulae develop symmetrically, with both sides adopting a pronounced leftward character. Tcf7l2 acts cell automously in nascent equipotential neurons, and on the right side, it promotes dHbm and suppresses dHbl differentiation. On the left, the parapineal prevents this Tcf7l2-dependent process, thereby promoting dHbl differentiation.ConclusionsTcf7l2 is essential for lateralized fate selection by habenular neurons that can differentiate along two alternative pathways, thereby leading to major neural circuit asymmetries.

BackgroundAlthough left-right asymmetries are common features of nervous systems, their developmental bases are largely unknown. In the zebrafish epithalamus, dorsal habenular neurons adopt medial (dHbm) and lateral (dHbl) subnuclear character at very different frequencies on the left and right sides. The left-sided parapineal promotes the elaboration of dHbl character in the left habenula, albeit by an unknown mechanism. Likewise, the genetic pathways acting within habenular neurons to control their asymmetric differentiated character are unknown.ResultsIn a forward genetic screen for mutations that result in loss of habenular asymmetry, we identified two mutant alleles of tcf7l2, a gene that encodes a transcriptional regulator of Wnt signaling. In tcf7l2 mutants, most neurons on both sides differentiate with dHbl identity. Consequently, the habenulae develop symmetrically, with both sides adopting a pronounced leftward character. Tcf7l2 acts cell automously in nascent equipotential neurons, and on the right side, it promotes dHbm and suppresses dHbl differentiation. On the left, the parapineal prevents this Tcf7l2-dependent process, thereby promoting dHbl differentiation.ConclusionsTcf7l2 is essential for lateralized fate selection by habenular neurons that can differentiate along two alternative pathways, thereby leading to major neural circuit asymmetries.

After a summary review of binary relations and their properties, it presents the main axioms used in the theory of choice. The several formulation of completeness and transitivity are used to outline their implications for discussing freedom and collective choice problems. After a chapter on revealed preference, the assumption of continuity is introduced and the main results on the representation of preferences. The following chapter discusses the axiom of rationality and its interpretations. The book ends with an introduction to the theory of choice under uncertainty.

Starting from a discussion of the simple Robinson economy, it gives an introduction to the basic tools of analysis for an economic system and the different approaches one can take. After discussing the main problems to be faced in going from the one agent to the multi agent case, it presents the theory of the consumer and that of the firm. The main results derived in these chapter are then use to give an outline of general equilibrium and welfare economics.

Lo sviluppo di imprese a forte impatto sociale e ambientale costituisce una leva fondamentale per lo sviluppo integrale per le aree più povere del pianeta.Dopo una classificazione dei vari modelli di social enterprise si analizzano le diverse iniziative poste in essere da istituzioni pubbliche, università e centri di ricerca e fondazioni per favorire il lancio e lo sviluppo di nuovi social business.