Taste Fragmentalism

This paper explores taste fragmentalism, a novel approach to matters of taste and faultless disagreement. The view is inspired by Kit Fine’s fragmentalism about time, according to which the temporal dimension can be constituted—in an absolute manner—by states that are pairwise incompatible, provided that they do not obtain together. In the present paper, we will apply this metaphysical framework to taste states. In our proposal, two incompatible taste states (such as the state of rhubarb’s being tasty and the state of rhubarb’s being distasteful) can both constitute reality in an absolute manner, although no agent can have joint access to both states. We will then develop a formalised version of our view by means of an exact truthmaker semantics for taste assertions. Within this framework—we argue—our linguistic and inferential practices concerning cases of faultless disagreement are elegantly vindi- cated, thus suggesting that taste fragmentalism is worth of further consideration

Prior antibiotics, proton pump inhibitors, and probiotics in patients with extensive stage small cell lung cancer treated with immune checkpoint blockade: A post-hoc analysis of the phase I/III IMpower 133 trial

The potential impact of concomitant medications such as systemic antibiotics, proton pump inhibitors (PPIs), and probiotics in patients with extensive-stage small cell lung cancer (ES-SCLC) receiving first-line chemo-immunotherapy combinations remains unclear. We ran a post hoc analysis of the IMpower133 phase I/III trial, which randomized patients with ES-SCLC to receive carboplatin/etoposide with either atezolizumab or placebo for 4 cycles, followed by maintenance therapy. We included any systemic antibiotic/probiotic exposure within 42 days prior to treatment initiation and any PPIs treatment within 30 days prior to treatment initiation. We explored the potential prognostic impact of antibiotics, PPIs and probiotics across the atezolizumab/chemotherapy and placebo/chemotherapy arms including the multivariable interaction term between the treatment modality and antibiotics/PPIs/probiotics. The analysis included 198 patients in the atezolizumab/chemotherapy arm and 195 in the placebo/chemotherapy arm. Baseline clinic-pathologic features were well balanced between the two cohorts, with 17 (8.6%) and 14 (7.2%) patients on antibiotics, 43 (21.7%) and 55 (28.2%) on PPIs, and 3 (1.5%) and 5 (2.6%) on probiotics among the atezolizumab/chemotherapy and placebo/chemotherapy cohorts, respectively. Exposure to antibiotics, PPIs, or probiotics was not associated with overall survival or progression free survival in either cohort. Furthermore, interaction terms between these medications and treatment modalities were not statistically significant. Baseline use of antibiotics, PPIs or probiotics did not influence clinical outcomes in patients with ES-SCLC treated with first-line atezolizumab/placebo plus chemotherapy, suggesting that they may not have a notable impact on clinical outcomes and could be considered for use in this patient population when necessary

Storia, religione, politica. Studi in onore di Maurilio Guasco

Storia, religione e politica sono gli interessi principali di Maurilio Guasco, figura di primo piano per la ricerca storica italiana, a cui è dedicato il presente volume, pubblicato in occasione del suo 85° compleanno. Amici, colleghi e allievi hanno voluto raccogliere una serie di studi, a testimonianza della stima e dell’affetto per l’uomo e per lo studioso, ma anche dell’impatto dei suoi lavori scientifici e del suo insegnamento. Il testo che ne è risultato è il frutto di un cammino condiviso con alcune delle persone che hanno avuto il privilegio di lavorare e dialogare con lui: un’opera miscellanea che è anzitutto un omaggio, ma che riflette anche – nella pluralità dei contributi – l’ampiezza dei suoi interessi e il profondo valore della sua eredità intellettuale

A scaling-and-squaring method for computing the inverses of matrix φ\varphi-functions

This paper aims to develop efficient numerical methods for computing the inverse of matrix $\varphi$-functions, $\psi_\ell(A):=(\varphi_\ell(A))^(-1)$, for $\ell = 1,2, \dots$ when A is a large and sparse matrix with eigenvalues in the open left half-plane. While $\varphi$-functions play a crucial role in the analysis and implementation of exponential integrators, their inverses arise in solving certain direct and inverse differential problems with non-local boundary conditions. We propose an adaptation of the standard scaling-and-squaring technique for computing $\psi_\ell(A)$, based on the Newton-Schulz iteration for matrix inversion. The convergence of this method is analyzed both theoretically and numerically. In addition, we derive and analyze Padé approximants for approximating $\psi_1(A/2^s)$, where s is a suitably chosen integer, necessary at the root of the squaring process. Numerical experiments demonstrate the effectiveness of the proposed approach

Chiral Switch of Gadopiclenol: New Standards in MRI Probes

Magnetic Resonance Imaging (MRI) plays a vital role in the accurate diagnosis of numerous human diseases and disorders, with Gd(III)-based contrast agents (GBCAs) being used in ≈30%–40% of procedures, resulting in ≈30 million doses administered annually worldwide. The careful design of a rigid macrocyclic chelator featuring a highly hydrophilic periphery leads to the development of gadopiclenol, the first bis-hydrated Gd(III)-based MRI contrast agent, recently approved for clinical use by both the FDA and EMA. The stereochemistry of the coordinating arms is found to play a crucial role in the remarkable thermodynamic stability and inertness of the Gd(III)-complex with the RRR/SSS-stereoisomer of this heptadentate chelating agent, ensuring its safety in vivo. The exceptional stability of the most effective gadopiclenol enantiomeric pair (RRR/SSS), coupled with a relaxivity 2 to 3 times higher than that of currently used GBCAs, has enabled the use of reduced doses while ensuring non-inferior image contrast

Postfazione a Giuseppe Di Luca: "La fede in tempo di pandemia"

Il lavoro di Giuseppe Di Luca affronta il tema del rapporto tra religione e pandemia con un approccio sociologico ed empirico. La pandemia ha risollevato un po' ovunque molte questioni rimaste in precedenza sopite, e ha sollecitato il ruolo delle Chiese e delle religioni nell'organizzare le chiusure e nel creare modalità alternative non solo per esercitare il culto, ma anche per garantire il supporto spirituale e materiale ai propri fedeli. Lo studio indaga tutto ciò in un caso particolare, quello del cattolicesimo in una piccola diocesi del Nord d'Italia, la diocesi di Alessandria

Deep immunophenotyping of circulating immune cells in major depressive disorder patients reveals immune correlates of clinical course and treatment response

Il Disturbo Depressivo Maggiore (MDD) è una condizione psichiatrica diffusa che impatta il funzionamento sociale e lavorativo, rendendolo una delle principali cause di disabilità. La diagnosi di MDD rimane clinica, basandosi sui criteri del Diagnostic and Statistical Manual of Mental Disorders (DSM)-5, poiché i biomarcatori non sono ancora stati validati per scopi diagnostici o come predittori della risposta al trattamento. Le strategie terapeutiche tradizionali spesso seguono un approccio uniforme, ottenendo risultati subottimali per molti pazienti che non sperimentano risposta o recupero. Diversi studi hanno riportato un'associazione tra MDD e disfunzione del sistema immunitario, ma pochi si sono concentrati sulla caratterizzazione approfondita delle cellule circolanti durante la fase acuta del MDD. Questo lavoro si è proposto di immunofenotipizzare le cellule del sangue periferico nella fase di ricaduta del disturbo, per identificare popolazioni cellulari rilevanti per il monitoraggio clinico dei pazienti. È stata condotta un'analisi multiparametrica sul sangue periferico di 60 pazienti con MDD utilizzando la citometria a flusso per identificare i linfociti (naive/effettori, memoria, regolatori) e le cellule mieloidi (cellule dendritiche, monociti). Sono state studiate le associazioni tra immunofenotipo, sintomi depressivi, funzionamento sociale e lavorativo e qualità della vita soggettiva durante la fase acuta e dopo tre mesi di trattamento. L'analisi multivariata ha mostrato che i CD4+ effettori terminalmente differenziati della memoria (TEMRA) erano associati a sintomi depressivi più gravi, con particolare enfasi sulle caratteristiche anedoniche e su un peggior funzionamento sociale e lavorativo e qualità della vita. I CD8+ TEMRA erano associati a sintomi depressivi legati alla disperazione. Al contrario, i Tregs ICOS+ erano associati a ideazioni suicide di bassa intensità, suggerendo un ruolo protettivo. I CD4+ effettori della memoria (EM) basali erano predittori negativi della riduzione dei sintomi depressivi dopo tre mesi di trattamento, mentre le cellule dendritiche plasmacitoidi (pDC) predicevano la riduzione della disperazione. Questi risultati confermano il coinvolgimento del sistema immunitario nel MDD e dimostrano l'esistenza di firme immunologiche associate alla gravità degli episodi depressivi maggiori e alla risposta al trattamento, che potrebbero guidare il monitoraggio clinico e future terapie personalizzate

Computing the action of the matrix generating function of Bernoulli polynomials on a vector with an application to non-local boundary value problems

This paper deals with efficient numerical methods for computing the action of the matrix generating function of Bernoulli polynomials, say q(τ, A), on a vector when A is a large and sparse matrix. This problem occurs when solving some non-local boundary value problems. Methods based on the Fourier expansion of q(τ, w) have already been addressed in the scientific literature. The contribution of this paper is twofold. First, we place these methods in the classical framework of Krylov-Lanczos (polynomial-rational) techniques for accelerating Fourier series. This allows us to apply the convergence results developed in this context to our function. Second, we design a new acceleration scheme. Some numerical results are presented to show the effectiveness of the proposed algorithms

Distal Radial Artery Approach for Invasive Blood Pressure Monitoring in Intensive Cardiac Care Unit

: Distal radial artery (dRA) is a novel vascular access site in interventional cardiology. We evaluated the use of dRA as alternative approach to standard forearm radial artery (fRA) for invasive blood pressure monitoring in Intensive Cardiac Care Unit (ICCU). This is a single-center, randomized, noninferiority trial. Patients admitted in ICCU needing invasive blood pressure monitoring were randomly allocated to dRA or fRA access site (1:1 ratio). Primary endpoint was noninferiority of dRA in the final catheterization success rate. Secondary endpoints were: first attempt success rates; arterial catheterization time; catheterization-related quality of pain; incidence of complications. A total of 250 patients were enrolled (125 in each arm). Final success rate was 95.2% in the dRA group versus 96.8% in the fRA arm (p <0.001 for noninferiority). First attempt success rates were 59.2% with dRA and 70.4% with fRA (p = 0.12). There was no difference in arterial catheterization time and catheterization-related quality of pain between the 2 arms. Entry-site complications were reduced with dRA (6.7% vs 17.4% in the fRA group; p = 0.013); this was mainly driven by decreased incidence of hematoma (0.8% vs 6.6%; p = 0.020). A numerically lower occurrence of arterial occlusion was observed with dRA (0.8% vs 4.9%; p = 0.06). In conclusion, in ICCU patients, the use of dRA to invasively monitor blood pressure is noninferior to fRA for catheterization success rates and may reduce entry-site bleeding

L’apport académique du recueil au-delà du droit international privé

Il diritto internazionale privato non può essere separato dal diritto comparato. Al di là della ricera del diritto straniero applicabile (che costituisce un soggetto di studio autonomo), il diritto comparato ricorda che ogni legislatore si rivolge ai giuristi del proprio sistema: utilizza convenzioni linguistiche, riferimenti impliciti a schemi concettuali che sono loro propri; nasconde nel non detto elementi che sembrano evidenti al giurista nazionale, ma che scompaiono agli occhi del giurista straniero e che a volte scompaiono anche agli occhi del giurista nazionale, pur rimanendo latenti nel sistema ( i c.d. crittotipi)