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1. Experimental Pharmacological Agents for the Treatment of Primary Biliary Cholangitis

Author

Floreani A

Subjects
pbc, treatment, ursodeoxycholic acid, obeticholic acid, fibrates, fxr agonists, ppar agonists, Therapeutics. Pharmacology, RM1-950
Abstract

Annarosa Floreani1,2 1University of Padova, Padova, Italy; 2Scientific Institute for Research, Hospitalization and Healthcare, Negrar, Verona, ItalyCorrespondence: Annarosa FloreaniUniversity of Padova, Padova, ItalyTel +10393899418841Email annarosa.floreani@unipd.itAbstract: The standard therapy for primary biliary cholangitis (PBC) is ursodeoxycholic acid (UDCA) which has shown to improve hepatic biochemistry, delay histological progression and improve transplant-free survival. Approximately 30– 40% of patients do not respond or are intolerant to UDCA. Obeticholic acid, a farnesoid X receptor (FXR) agonist is the only agent approved by the Food and Drug Administration for patients who do not respond to UDCA. Recently, combination therapy with UDCA and bezafibrate has been shown to improve biochemistry and both GLOBE and UK-PBC score in patients with an inadequate response to UDCA. More recently, new pharmacological agents have been included in Phase 2 and Phase 3 trials: PPAR agonists, non-bile acid FXR agonists, anti-NOX agents, immunomodulators and mesenchymal stem cells transplantation. This review gives an overview on the current experimental pharmacological agents employed in the treatment of PBC.Keywords: PBC, treatment, ursodeoxycholic acid, obeticholic acid, fibrates, FXR agonists, PPAR agonists

Published
2020

3. Representations of the $su(1,1)$ current algebra and probabilistic perspectives

Author

Floreani, Simone, Jansen, Sabine, and Wagner, Stefan

Subjects
Mathematics - Probability, Mathematical Physics, 81R10, 33C45, 60K35, 60H40
Abstract

We construct three representations of the $su(1,1)$ current algebra: in extended Fock space, with Gamma random measures, and with negative binomial (Pascal) point processes. For the second and third representations, the lowering and neutral operators are generators of measure-valued branching processes (Dawson-Watanabe superprocesses) and spatial birth-death processes. The vacuum is the constant function $1$ and iterated application of raising operators yields Laguerre and Meixner polynomials. In addition, we prove a Baker-Campbell-Hausdorff formula and give an explicit formula for the action of unitaries $\exp( k^+(\xi) - k^-(\xi))\exp(2 \mathrm i k^0(\theta))$ on exponential vectors. We explain how the representations fit in with a general scheme proposed by Araki and with representations of the $SL(2,\mathbb{R})$ current group with Vershik, Gelfand and Graev's multiplicative measure., Comment: 36 pages

Published
2024

4. Intertwinings for Continuum Particle Systems: an Algebraic Approach

Author

Floreani, Simone, Jansen, Sabine, and Wagner, Stefan

Subjects
Mathematics - Probability, Mathematical Physics, Mathematics - Functional Analysis, 60J25, 60K35, 82C22, 22E60
Abstract

We develop the algebraic approach to duality, more precisely to intertwinings, within the context of particle systems in general spaces, focusing on the $\mathfrak{su}(1,1)$ current algebra. We introduce raising, lowering, and neutral operators indexed by test functions and we use them to construct unitary operators, which act as self-intertwiners for some Markov processes having the Pascal process's law as a reversible measure. We show that such unitaries relate to generalized Meixner polynomials. Our primary results are continuum counterparts of results in the discrete setting obtained by Carinci, Franceschini, Giardin\`a, Groenevelt, and Redig (2019).

Published
2023
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6. Non-equilibrium steady state of the symmetric exclusion process with reservoirs

Author

Floreani, Simone and Casanova, Adrián González

Subjects
Mathematics - Probability, Condensed Matter - Statistical Mechanics, Mathematical Physics, 60K35, 82C22, 60K37, 82C23
Abstract

Consider the open symmetric exclusion process on a connected graph with vertexes in $[N-1]:=\{1,\ldots, N-1\}$ where points $1$ and $N-1$ are connected, respectively, to a left reservoir and a right reservoir with densities $\rho_L,\rho_R\in(0,1)$. We prove that the non-equilibrium steady state of such system is $$\mu_{\text{stat}} = \sum_{I\subset \mathcal P([N-1]) }F(I)\bigg(\otimes_{x\in I}\rm{Bernoulli}(\rho_R)\otimes_{y\in [N-1]\setminus I}\rm{Bernoulli}(\rho_L) \bigg).$$ In the formula above $ \mathcal P([N-1])$ denotes the power set of $[N-1]$ while the numbers $F(I)> 0$ are such that $\sum_{I\subset \mathcal P([N-1]) }F(I)=1$ and given in terms of absorption probabilities of the absorbing stochastic dual process. Via probabilistic arguments we compute explicitly the factors $F(I)$ when the graph is a homogeneous segment.

Published
2023

9. From quenched invariance principle to semigroup convergence with applications to exclusion processes

Author

Chiarini, Alberto, Floreani, Simone, and Sau, Federico

Subjects
Mathematics - Probability, Mathematical Physics, 60K35, 60K37, 60G22, 35B27, 60F17, 82C41, 82B43
Abstract

Consider a random walk on $\mathbb{Z}^d$ in a translation-invariant and ergodic random environment and starting from the origin. In this short note, assuming that a quenched invariance principle for the opportunely-rescaled walks holds, we show how to derive an $L^1$-convergence of the corresponding semigroups. We then apply this result to obtain a quenched pathwise hydrodynamic limit for the simple symmetric exclusion process on $\mathbb{Z}^d$, $d\ge 2$, with i.i.d. symmetric nearest-neighbors conductances $\omega_{xy}\in [0,\infty)$ only satisfying $$\mathbb{Q}(\omega_{xy}>0)>p_c\ ,$$ where $p_c$ is the critical value for bond percolation.

Published
2023

10. Fractional kinetics equation from a Markovian system of interacting Bouchaud trap models

Author

Chiarini, Alberto, Floreani, Simone, and Sau, Federico

Subjects
Mathematics - Probability, Mathematical Physics, 60K35, 60K37, 60G57, 60G22, 35B27
Abstract

We consider a partial exclusion process evolving on $\mathbb Z^d$ in a random trapping environment. In dimension $d\ge 2$, we derive the fractional kinetics equation \begin{equation*}\frac{\partial^\beta\rho_t}{\partial t^\beta} = \Delta \rho_t \end{equation*} as a hydrodynamic limit of the particle system. Here, $\frac{\partial^\beta}{\partial t^\beta}$, $\beta\in(0,1)$, denotes the fractional derivative in the Caputo sense. We thus exhibit a Markovian interacting particle system whose empirical density field rescales to a sub-diffusive equation corresponding to a non-Markovian process, the Fractional Kinetics process. In contrast, we show that, when $d=1$, the system rescales to the solution to \begin{equation*} \frac{\partial \rho_t}{\partial t}= \mathcal L_\beta \rho_t\ , \end{equation*} where $\mathcal L_\beta$ is the random generator of the singular quasi-diffusion known as FIN diffusion.

Published
2023

11. Loss of biochemical response at any time worsens outcomes in UDCA-treated patients with primary biliary cholangitis

Author

Surain B. Roberts, Woo Jin Choi, Lawrence Worobetz, Catherine Vincent, Jennifer A. Flemming, Angela Cheung, Karim Qumosani, Mark Swain, Dusanka Grbic, Hin Hin Ko, Kevork M. Peltekian, Lusine Abrahamyan, Monika Saini, Kattleya Tirona, Bishoi Aziz, Ellina Lytvyak, Pietro Invernizzi, Cyriel Y. Ponsioen, Tony Bruns, Nora Cazzagon, Keith Lindor, George N. Dalekos, Nikolaos K. Gatselis, Xavier Verhelst, Annarosa Floreani, Christophe Corpechot, Marlyn J. Mayo, Cynthia Levy, Maria-Carlota Londoño, Pier M. Battezzati, Albert Pares, Frederik Nevens, Adriaan van der Meer, Kris V. Kowdley, Palak J. Trivedi, Ana Lleo, Douglas Thorburn, Marco Carbone, Nazia Selzner, Aliya F. Gulamhusein, Harry LA. Janssen, Aldo J. Montano-Loza, Andrew L. Mason, Gideon M. Hirschfield, and Bettina E. Hansen

Subjects
UDCA, liver transplantation, prognostication, alkaline phosphatase, total bilirubin, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: Biochemical response to ursodeoxycholic acid (UDCA) therapy is associated with good prognosis in people living with primary biliary cholangitis (PBC). Biochemical response is typically assessed early in disease and it is not known what proportion of patients lose previously attained biochemical response, nor whether this impacts long-term liver transplant (LT)-free survival. Methods: We identified all UDCA-treated patients with PBC from the Canadian Network for Autoimmune Liver disease with biochemical measurements at 1 year, and evaluated their liver biochemistry over time. Inadequate biochemical response was defined as serum alkaline phosphatase ≥1.67x the upper limit of normal or abnormal serum total bilirubin at 1 year of UDCA therapy and all time points thereafter. Multistate Markov models were used to estimate transition rates between biochemical response states and from each state to LT or death. Results were validated in an external cohort (GLOBAL PBC registry). Results: A total of 823 patients from eight centers were included. Mean age at diagnosis was 53 years, 91% were female, 33% had inadequate biochemical response to UDCA at 1 year (n = 269). Patients who retained initial adequate response had lower rates of LT or death compared to patients who subsequently lost response (relative rate 0.102, 95% CI 0.047-0.223). Patients who regained adequate response had lower rates than patients who did not (0.016, 95% CI 0.001-0.568), and patients who lost response once more (0.010, 95% CI 0.001-0.340). Patients who regained adequate response for a third time also had lower rates than patients who did not (0.151, 95% CI 0.040-0.566). Analyses in the GLOBAL PBC registry (n = 2,237) validated these results. Conclusion: Loss of biochemical response at any time is associated with heightened risks of LT or death in people living with PBC. Achievement of biochemical response is an important goal throughout follow-up, regardless of biochemical response profile early in therapy. Impact and implications:: Early biochemical response to ursodeoxycholic acid is associated with good prognosis in patients with primary biliary cholangitis (PBC). Our work demonstrates that patients with PBC transition between biochemical response states over time, and that these transitions correspond with changes in risk of liver transplantation or death. Clinicians should re-evaluate risk and optimize treatment decisions for patients with PBC throughout follow-up, regardless of early biochemical response to therapy.

Published
2024
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15. Loss of biochemical response at any time worsens outcomes in UDCA-treated patients with primary biliary cholangitis

Author

Roberts, Surain B., Choi, Woo Jin, Worobetz, Lawrence, Vincent, Catherine, Flemming, Jennifer A., Cheung, Angela, Qumosani, Karim, Swain, Mark, Grbic, Dusanka, Ko, Hin Hin, Peltekian, Kevork M., Abrahamyan, Lusine, Saini, Monika, Tirona, Kattleya, Aziz, Bishoi, Lytvyak, Ellina, Invernizzi, Pietro, Ponsioen, Cyriel Y., Bruns, Tony, Cazzagon, Nora, Lindor, Keith, Dalekos, George N., Gatselis, Nikolaos K., Verhelst, Xavier, Floreani, Annarosa, Corpechot, Christophe, Mayo, Marlyn J., Levy, Cynthia, Londoño, Maria-Carlota, Battezzati, Pier M., Pares, Albert, Nevens, Frederik, van der Meer, Adriaan, Kowdley, Kris V., Trivedi, Palak J., Lleo, Ana, Thorburn, Douglas, Carbone, Marco, Selzner, Nazia, Gulamhusein, Aliya F., Janssen, Harry LA., Montano-Loza, Aldo J., Mason, Andrew L., Hirschfield, Gideon M., and Hansen, Bettina E.

Published
2024
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16. Prognostic scores for ursodeoxycholic acid-treated patients predict graft loss and mortality in recurrent primary biliary cholangitis after liver transplantation

Author

Montano-Loza, Aldo J., Lytvyak, Ellina, Hirschfield, Gideon, Hansen, Bettina E., Ebadi, Maryam, Berney, Thierry, Toso, Christian, Magini, Giulia, Villamil, Alejandra, Nevens, Frederik, Van den Ende, Natalie, Pares, Albert, Ruiz, Pablo, Terrabuio, Débora, Trivedi, Palak J., Abbas, Nadir, Donato, Maria Francesca, Yu, Lei, Landis, Charles, Dumortier, Jérôme, Dyson, Jessica Katharine, van der Meer, Adriaan J., de Veer, Rozanne, Pedersen, Mark, Mayo, Marlyn, Manns, Michael P., Taubert, Richard, Kirchner, Theresa, Belli, Luca S., Mazzarelli, Chiara, Stirnimann, Guido, Floreani, Annarosa, Cazzagon, Nora, Russo, Francesco Paolo, Burra, Patrizia, Zigmound, Udi, Houri, Inbal, Carbone, Marco, Mulinacci, Giacomo, Fagiuoli, Stefano, Pratt, Daniel Stephan, Bonder, Alan, Schiano, Thomas D., Haydel, Brandy, Lohse, Ansgar, Schramm, Christoph, Rüther, Darius, Casu, Stefania, Verhelst, Xavier, Beretta-Piccoli, Benedetta Terziroli, Robles, Mercedes, Mason, Andrew L., and Corpechot, Christophe

Published
2024
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17. Boundary driven Markov gas: duality and scaling limits

Author

Carinci, Gioia, Floreani, Simone, Giardinà, Cristian, and Redig, Frank

Subjects
Mathematics - Probability, Mathematical Physics, 60J70, 60K35, 82C22
Abstract

Inspired by the recent work of Bertini and Posta, who introduced the boundary driven Brownian gas on $[0,1]$, we study boundary driven systems of independent particles in a general setting, including particles jumping on finite graphs and diffusion processes on bounded domains in $\mathbb{R}^d$. We prove duality with a dual process that is absorbed at the boundaries, thereby creating a general framework that unifies dualities for boundary driven systems in the discrete and continuum setting. We use duality first to show that from any initial condition the systems evolve to the unique invariant measure, which is a Poisson point process with intensity the solution of a Dirichlet problem. Second, we show how the boundary driven Brownian gas arises as the diffusive scaling limit of a system of independent random walks coupled to reservoirs with properly rescaled intensity., Comment: 30 pages

Published
2021

18. Intertwining and Duality for Consistent Markov Processes

Author

Floreani, Simone, Jansen, Sabine, Redig, Frank, and Wagner, Stefan

Subjects
Mathematics - Probability, Mathematical Physics, Mathematics - Functional Analysis, 60J70, 60K35, 82C22
Abstract

In this paper we derive intertwining relations for a broad class of conservative particle systems both in discrete and continuous setting. Using the language of point process theory, we are able to derive a natural framework in which duality and intertwining can be formulated. We prove falling factorial and orthogonal polynomial intertwining relations in a general setting. These intertwinings unite the previously found classical and orthogonal self-dualities in the context of discrete particle systems and provide new dualities for several interacting systems in the continuum. We also introduce a new process, the symmetric inclusion process in the continuum, for which our general method applies and yields generalized Meixner polynomials as orthogonal self-intertwiners.

Published
2021

22. Surveillance of Vermont wildlife in 2021–2022 reveals no detected SARS-CoV-2 viral RNA

Author

Despres, Hannah W., Mills, Margaret G., Schmidt, Madaline M., Gov, Jolene, Perez, Yael, Jindrich, Mars, Crawford, Allison M. L., Kohl, Warren T., Rosenblatt, Elias, Kubinski, Hannah C., Simmons, Benjamin C., Nippes, Miles C., Goldenberg, Anne J., Murtha, Kristina E., Nicoloro, Samantha, Harris, Mia J., Feeley, Avery C., Gelinas, Taylor K., Cronin, Maeve K., Frederick, Robert S., Thomas, Matthew, Johnson, Meaghan E., Murphy, James, Lenzini, Elle B., Carr, Jr., Peter A., Berger, Danielle H., Mehta, Soham P., Floreani, Christopher J., Koval, Amelia C., Young, Aleah L., Fish, Jess H., Wallace, Jack, Chaney, Ella, Ushay, Grace, Ross, Rebecca S., Vostal, Erin M., Thisner, Maya C., Gonet, Kyliegh E., Deane, Owen C., Pelletiere, Kari R., Rockafeller, Vegas C., Waterman, Madeline, Barry, Tyler W., Goering, Catriona C., Shipman, Sarah D., Shiers, Allie C., Reilly, Claire E., Duff, Alanna M., Madruga, Sarah L., Shirley, David J., Jerome, Keith R., Pérez-Osorio, Ailyn C., Greninger, Alexander L., Fortin, Nick, Mosher, Brittany A., and Bruce, Emily A.

Published
2023
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23. Interlaminar fracture behaviour of fibre reinforced powder epoxy composites

Author

Floreani, Christophe, Ó Brádaigh, Conchúr, Davies, Peter, Alam, Parvez, and Stratford, Timothy

Abstract

The aim of this work is to study delamination in fibre reinforced composites with applications in wind and tidal turbine blades. Powder epoxy composites are a very promising option for the manufacturing of large composite structures due to their low exotherm and viscosity, a suitability for out-of-autoclave manufacturing and their ability to perform a separate melting and curing phase allowing complicated parts such as wind turbine blades to be formed separately and cured in a one-shot process. It was shown that quasi-unidirectional carbon fibre and glass fibre reinforced powder epoxy composites could be manufactured out-of-autoclave with a low void content. However, a relatively high variation in the thickness between samples and fibre distortion, especially in the CFRP samples were measured. This shows that, although powder epoxy is a promising resin for the manufacturing of composites, an automated process such as the fabrication of powder epoxy prepregs is preferable to the hand spraying process for the fabrication of consistent composites. The powder epoxy resin was show to be very ductile with a strain to failure of nearly 10%. However, it lies within the mid-range of reported strength values for epoxy with an ultimate strength of 61 MPa and in the low range of reported elastic modulus values with a value of 1.64GPa. The tensile properties of powder epoxy composites were shown to be comparable to those of commonly used epoxy resins but the compressive strength was shown to be quite low with a 48% and 59% reduction for the GFRP and CFRP composites compared to their tensile strengths. The interlaminar fracture toughness of carbon and glass fibre composites was studied in pure mode I by performing Double Cantilever Beam (DCB) tests and at 25% mode II, 50% mode II and 75% mode II by performing Mixed Mode Bending (MMB) testing and in pure mode II by performing an End-Loaded Specimen (ELS) test. The strain energy release rate (SERR) at both crack initiation and propagation were shown to be significantly higher than both conventional and toughened epoxy composites for which published data is available. While the powder epoxy is not the only factor explaining the high fracture toughness, with the off-axis fibres, evidenced by fibre bridging, played a role, the powder epoxy composites used in this study still had a higher toughness than published data for epoxy quasi-unidirectional fabrics which also contain off-axis fibers. To understand the influence of moisture on the mechanical properties of the studied powder epoxy composites, they were hygrothermally aged in 60°C seawater. The CFRP and GFRP samples were saturated after around 4 months. Water diffusion in the composites induced plasticisation of the resin, leading to a 25°C reduction in the resin Tg. The longitudinal elastic modulus of the CFRP and GFRP were unaffected by the presence of water but reductions in the longitudinal, transverse and shear strengths of 45-50% and 15-30% were measured for the GFRP and CFRP respectively. SEM micrographs showed a degradation in the fibre/matrix interfacial strength, especially in the GFRP samples. In contrast, water absorption reduced the compressive strength properties of CFRP to a greater degree than GFRP. Hygrothermal ageing led to reductions in the interlaminar fracture toughness but the reductions were dependent on the mode ratio. The propagation GC decreased between 25% for mode I and 40% for mode II for the GFRP samples, while a 25% decrease in the mode I was observed for CFRP while the mode II Gc remained unaffected. The degradation of the fibre/matrix interface was a likely explanation for the reduction in mode I toughness for the CFRP as fibre pull-out likely occurred at a lower energy while the 90° fibres of the UD glass fabric were not able to arrest mode II crack growth as efficiently. A finite element delamination analysis was carried out using the virtual crack closing technique (VCCT). A parametric model was developed to allow for automated modelling of a variety of ply drop configurations. This was followed by a sensitivity analysis to understand the influence of the various model parameters on the predicted delamination failure load. Finally, a method was developed for the optimization of chamfered ply drop specimens with regards to the chamfered slope ratio and the vertical height at the end of the ply drop, called the toe height. It was shown that the delamination failure load increased with the chamfered slope ratio but decreased as the toe height increased. As a result of this study, the combination of chamfer slope and vertical height leading to failure in the plank occurring prior to delamination initiation were obtained, allowing for the manufacturing of chamfered ply drops where the risk of delamination is suppressed. The methodology for the characterisation of the fatigue delamination properties needed for an accurate prediction of delamination growth under fatigue loading was defined. Then a finite element predicting fatigue crack growth in chamfered ply drop specimens, based on the Paris law and VCCT models to extract SERR as a function of crack length and applied strain, was developed for a variety of geometric configurations. The comparison of predicted fatigue life with experimental results shows that the FE model captured the same trends observed during testing, but the predicted strain values leading to a given number of cycles to failure were up to 30\% different from the experimental ones. In the absence of fatigue delamination properties for the materials used in this study, the fatigue life predictions were carried out using Paris law parameters obtained from literature, giving a likely explanation for this relatively large difference.

Published
2022
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24. Switching interacting particle systems: scaling limits, uphill diffusion and boundary layer

Author

Floreani, Simone, Giardinà, Cristian, Hollander, Frank den, Nandan, Shubhamoy, and Redig, Frank

Subjects
Mathematics - Probability, Mathematical Physics, 60J70, 60K35 (Primary), 82C26, 92D25 (Secondary)
Abstract

In this paper we consider three classes of interacting particle systems on $\mathbb Z$: independent random walks, the exclusion process, and the inclusion process. We allow particles to switch their jump rate (the rate identifies the type of particle) between $1$ (fast particles) and $\epsilon\in[0,1]$ (slow particles). The switch between the two jump rates happens at rate $\gamma\in(0,\infty)$. In the exclusion process, the interaction is such that each site can be occupied by at most one particle of each type. In the inclusion process, the interaction takes places between particles of the same type at different sites and between particles of different type at the same site. We derive the macroscopic limit equations for the three systems, obtained after scaling space by $N^{-1}$, time by $N^2$, the switching rate by $N^{-2}$, and letting $N\to\infty$. The limit equations for the macroscopic densities associated to the fast and slow particles is the well-studied double diffusivity model. This system of reaction-diffusion equations was introduced to model polycrystal diffusion and dislocation pipe diffusion, with the goal to overcome the limitations imposed by Fick's law. In order to investigate the microscopic out-of-equilibrium properties, we analyse the system on $[N]=\{1,\ldots,N\}$, adding boundary reservoirs at sites $1$ and $N$ of fast and slow particles, respectively. Inside $[N]$ particles move as before, but now particles are injected and absorbed at sites $1$ and $N$ with prescribed rates that depend on the particle type. We compute the steady-state density profile and the steady-state current. It turns out that uphill diffusion is possible, i.e., the total flow can be in the direction of increasing total density. This phenomenon, which cannot occur in a single-type particle system, is a violation of Fick's law made possible by the switching between types.

Published
2021
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28. Predicting spring phenology in deciduous broadleaf forests: NEON phenology forecasting community challenge

Author

Wheeler, Kathryn I., Dietze, Michael C., LeBauer, David, Peters, Jody A., Richardson, Andrew D., Ross, Arun A., Thomas, R. Quinn, Zhu, Kai, Bhat, Uttam, Munch, Stephan, Floreani Buzbee, Raphaela, Chen, Min, Goldstein, Benjamin, Guo, Jessica, Hao, Dalei, Jones, Chris, Kelly-Fair, Mira, Liu, Haoran, Malmborg, Charlotte, Neupane, Naresh, Pal, Debasmita, Shirey, Vaughn, Song, Yiluan, Steen, McKalee, Vance, Eric A., Woelmer, Whitney M., Wynne, Jacob H., and Zachmann, Luke

Published
2024
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29. Dynamics of Liver Stiffness Measurement and Clinical Course of Primary Biliary Cholangitis

Author

Lam, Laurent, Soret, Pierre-Antoine, Lemoinne, Sara, Hansen, Bettina, Hirschfield, Gideon, Gulamhusein, Aliya, Montano-Loza, Aldo J., Lytvyak, Ellina, Parés, Albert, Olivas, Ignasi, Londono, Maria-Carlota, Rodríguez-Tajes, Sergio, Eaton, John E., Osman, Karim T., Schramm, Christoph, Sebode, Marcial, Lohse, Ansgar W., Dalekos, George, Gatselis, Nikolaos, Nevens, Frederik, Cazzagon, Nora, Zago, Alessandra, Russo, Francesco Paolo, Floreani, Annarosa, Abbas, Nadir, Trivedi, Palak, Thorburn, Douglas, Saffioti, Francesca, Barkai, Laszlo, Roccarina, Davide, Calvaruso, Vicenza, Fichera, Anna, Delamarre, Adèle, Sobenko, Natalia, Villamil, Alejandra Maria, Medina-Morales, Esli, Bonder, Alan, Patwardhan, Vilas, Rigamonti, Cristina, Carbone, Marco, Invernizzi, Pietro, Cristoferi, Laura, van der Meer, Adriaan, de Veer, Rozanne, Zigmond, Ehud, Yehezkel, Eyal, Kremer, Andreas E., Deibel, Ansgar, Bruns, Tony, Große, Karsten, Wetten, Aaron, Dyson, Jessica Katharine, Jones, David, Levy, Cynthia, Tanaka, Atsushi, Dumortier, Jérôme, Pageaux, Georges-Philippe, de Lédinghen, Victor, Carrat, Fabrice, Chazouillères, Olivier, and Corpechot, Christophe

Published
2024
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30. Development and Validation of a Scoring System to Predict Response to Obeticholic Acid in Primary Biliary Cholangitis

Author

Scaravaglio, Miki, Nofit, Eugenia, Gallo, Paolo, Galati, Giovanni, Pezzato, Francesco, Rollo, Paolo, D’Ovidio, Erica, Coco, Barbara, Tortora, Annalisa, Fiorini, Cecilia, Venere, Rosanna, Scifo, Gaetano, Cannavò, Mariarita, Feletti, Valentina, Pizzolante, Fabrizio, Giannini, Edoardo Giovanni, Cotugno, Rosa, Fanella, Silvia, Losito, Francesco, Grassi, Giuseppe, Manfredi, Giulia Francesca, Buzzanca, Valerio, Omazzi, Barbara, Casella, Silvia, Zani, Francesca, Ricci, Chiara, Bellia, Valentina, Abenavoli, Ludovico, Morelli, Olivia, Crocè, Lory Saveria, Scivetti, Paolo, Panero, Antonio, Boano, Valentina, Poggi, Guido, Gimignani, Giancarlo, Conforti, Alessandro, Frazzetto, Evelise, Rapisarda, Laura, Demma, Shrin, De Vincentis, Antonio, Ampuero, Javier, Terracciani, Francesca, D’Amato, Daphne, Gerussi, Alessio, Cristoferi, Laura, Cazzagon, Nora, Bonaiuto, Emanuela, Floreani, Annarosa, Calvaruso, Vincenza, Cadamuro, Luca, Degasperi, Elisabetta, Morgando, Anna, Vanni, Ester, Lleo, Ana, Colapietro, Francesca, Alvaro, Domenico, Castellaneta, Antonino, Labanca, Sara, Viganò, Mauro, Distefano, Marco, Pace Palitti, Valeria, De Matthaeis, Nicoletta, Marzioni, Marco, Gómez-Dominguez, Elena, Montero, Jose-Luis, Molina, Esther, Garcia-Buey, Luisa, Casado, Marta, Berenguer, Marina, Conde, Isabel, Simon, Miguel-Angel, Fuentes, Javier, Costa-Moreira, Pedro, Macedo, Guilherme, Jorquera, Francisco, Morillas, Rosa-Maria, Presa, Jose, Sousa, Jose-Manuel, Gomes, Dario, Santos, Luis, Olveira, Antonio, Hernandez-Guerra, Manuel, Aburruza, Leire, Santos, Arsenio, Carvalho, Armando, Uriz, Juan, Gutierrez, Maria-Luisa, Perez, Elia, Chessa, Luchino, Pellicelli, Adriano, Marignani, Massimo, Muratori, Luigi, Niro, Grazia Anna, Brunetto, Maurizia, Ponziani, Francesca Romana, Pompili, Maurizio, Marra, Fabio, Galli, Andrea, Mussetto, Alessandro, Alagna, Giuliano, Simone, Loredana, Bertino, Gaetano, Rosina, Floriano, Cozzolongo, Raffaele, Russello, Maurizio, Baiocchi, Leonardo, Saitta, Carlo, Terreni, Natalia, Zolfino, Teresa, Rigamonti, Cristina, Vigano, Raffaella, Cuccorese, Giuseppe, Pozzoni, Pietro, Pedone, Claudio, Grasso, Simone, Picardi, Antonio, Invernizzi, Pietro, Sacco, Rodolfo, Izzi, Antonio, Fernandez-Rodriguez, Conrado, Vespasiani-Gentilucci, Umberto, and Carbone, Marco

Published
2024
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34. Orthogonal polynomial duality of boundary driven particle systems and non-equilibrium correlations

Author

Floreani, Simone, Redig, Frank, and Sau, Federico

Subjects
Mathematics - Probability, Mathematical Physics, 60K35 (Primary), 60K37, 60J75, 82C05 (Secondary)
Abstract

We consider symmetric partial exclusion and inclusion processes in a general graph in contact with reservoirs, where we allow both for edge disorder and well-chosen site disorder. We extend the classical dualities to this context and then we derive new orthogonal polynomial dualities. From the classical dualities, we derive the uniqueness of the non-equilibrium steady state and obtain correlation inequalities. Starting from the orthogonal polynomial dualities, we show universal properties of n-point correlation functions in the non-equilibrium steady state for systems with at most two different reservoir parameters, such as a chain with reservoirs at left and right ends., Comment: 34 pages, 1 figure

Published
2020
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35. Prevalence and significance of antimitochondrial antibodies in autoimmune hepatitis (AIH): Results from a large multicentre study of the International AIH Group

Author

Gatselis, Nikolaos K., Zachou, Kalliopi, Loza, Aldo J. Montano, Cançado, Eduardo Luiz Rachid, Arinaga-Hino, Teruko, Muratori, Paolo, Efe, Cumali, Floreani, Annarosa, Invernizzi, Pietro, Takahashi, Athushi, Takaki, Akinobu, Beretta-Piccoli, Benedetta Terziroli, van Hoek, Bart, Lytvyak, Ellina, Guedes, Laura Vilar, Purnak, Tugrul, Cazzagon, Nora, Lygoura, Vasiliki, Arvaniti, Pinelopi, Rigopoulou, Eirini I., Muratori, Luigi, and Dalekos, George N.

Published
2023
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38. Influence of Vineyard Inter-Row Management on Grapevine Leafhoppers and Their Natural Enemies

Author

Elena Cargnus, Seyedeh Fatemeh Kiaeian Moosavi, Davide Frizzera, Chiara Floreani, Pietro Zandigiacomo, Giovanni Bigot, Davide Mosetti, and Francesco Pavan

Subjects
Araneae, alternate mowing, Anagrus atomus, egg parasitoid, Hebata vitis, spiders, Science
Abstract

Inter-row management in vineyards can influence the abundance of grapevine pests and their natural enemies. In 2013–2015, in a vineyard in northeastern Italy, the influence of two vineyard inter-row management strategies (i.e., alternate mowing, AM, and periodical tillage, PT) on the population dynamics of grapevine leafhoppers Hebata vitis and Zygina rhamni and their natural enemies, the mymarid Anagrus atomus and spiders (Araneae), and other hymenopteran parasitoids, were studied with different survey approaches. The infestations of both leafhoppers were lower in AM than PT due to the reduced leafhopper oviposition and higher nymph mortality in AM. This occurred although leafhopper egg parasitization by A. atomus was greater in PT than AM according to a density-dependent relationship with the leafhopper egg amount. Hymenopteran parasitoids other than A. atomus were the most abundant in AM, probably due to the higher availability of nectar and pollen than in PM. The significantly higher population densities of hunting spiders in AM than PT can be associated with the higher predation of leafhopper nymphs. Therefore, the study demonstrated that the alternate mowing of vineyard inter-rows enhances the abundance of natural enemies, such as spiders and hymenopteran parasitoids, and can contribute to grapevine leafhopper pest control.

Published
2024
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39. Are Gender Differences Important for Autoimmune Liver Diseases?

Author

Annarosa Floreani, Daniela Gabbia, and Sara De Martin

Subjects
gender differences, primary biliary cholangitis, primary sclerosing cholangitis, AIH, IgG4-related disease, Science
Abstract

Gender Medicine has had an enormous expansion over the last ten years. Autoimmune liver diseases include several conditions, i.e., autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and conditions involving the liver or biliary tree overlapping with AIH, as well as IgG4-related disease. However, little is known about the impact of sex in the pathogenesis and natural history of these conditions. The purpose of this review is to provide an update of the gender disparities among the autoimmune liver diseases by reviewing the data published from 1999 to 2023. The epidemiology of these diseases has been changing over the last years, due to the amelioration of knowledge in their diagnosis, pathogenesis, and treatment. The clinical data collected so far support the existence of sex differences in the natural history of autoimmune liver diseases. Notably, their history could be longer than that which is now known, with problems being initiated even at a pediatric age. Moreover, gender disparity has been observed during the onset of complications related to end-stage liver disease, including cancer incidence. However, there is still an important debate among researchers about the impact of sex and the pathogenesis of these conditions. With this review, we would like to emphasize the urgency of basic science and clinical research to increase our understanding of the sex differences in autoimmune liver diseases.

Published
2024
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41. Hydrodynamics for the partial exclusion process in random environment

Author

Floreani, Simone, Redig, Frank, and Sau, Federico

Subjects
Mathematics - Probability
Abstract

In this paper, we introduce a random environment for the exclusion process in $\mathbb{Z}^d$ obtained by assigning a maximal occupancy to each site. This maximal occupancy is allowed to randomly vary among sites, and partial exclusion occurs. Under the assumption of ergodicity under translation and uniform ellipticity of the environment, we derive a quenched hydrodynamic limit in path space by strengthening the mild solution approach initiated in [39] and [21]. To this purpose, we prove, employing the technology developed for the random conductance model, a homogenization result in the form of an arbitrary starting point quenched invariance principle for a single particle in the same environment, which is a result of independent interest. The self-duality property of the partial exclusion process allows us to transfer this homogenization result to the particle system and, then, apply the tightness criterion in [40]., Comment: 34 pages, 1 figure

Published
2019
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42. A randomized, placebo-controlled, phase II study of obeticholic acid for primary sclerosing cholangitis

Author

Kowdley, Kris V, Vuppalanchi, Raj, Levy, Cynthia, Floreani, Annarosa, Andreone, Pietro, LaRusso, Nicholas F, Shrestha, Roshan, Trotter, James, Goldberg, David, Rushbrook, Simon, Hirschfield, Gideon M, Schiano, Thomas, Jin, Yuying, Pencek, Richard, MacConell, Leigh, Shapiro, David, Bowlus, Christopher L, and Investigators, AESOP Study

Subjects
Clinical Trials and Supportive Activities, Clinical Research, Rare Diseases, Liver Disease, Patient Safety, Digestive Diseases, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Alkaline Phosphatase, Chenodeoxycholic Acid, Cholagogues and Choleretics, Dose-Response Relationship, Drug, Double-Blind Method, Drug Monitoring, Female, Humans, Liver Cirrhosis, Biliary, Liver Function Tests, Male, Middle Aged, Pruritus, Treatment Outcome, Cholestasis, Farnesoid X receptor, Ursodeoxycholic acid, AESOP Study Investigators, Clinical Sciences, Public Health and Health Services, Gastroenterology & Hepatology
Abstract

Background & aimsPrimary sclerosing cholangitis (PSC) is a rare, cholestatic liver disease with no currently approved therapies. Obeticholic acid (OCA) is a potent farnesoid X receptor (FXR) agonist approved for the treatment of primary biliary cholangitis. We investigated the efficacy and safety of OCA in patients with PSC.MethodsAESOP was a phase II, randomized, double-blind, placebo-controlled, dose-finding study. Eligible patients were 18 to 75 years of age with a diagnosis of PSC and serum alkaline phosphatase (ALP) ≥2× the upper limit of normal (ULN) and total bilirubin

Published
2020

43. Effects of Vedolizumab in Patients With Primary Sclerosing Cholangitis and Inflammatory Bowel Diseases

Author

Lynch, Kate D, Chapman, Roger W, Keshav, Satish, Montano-Loza, Aldo J, Mason, Andrew L, Kremer, Andreas E, Vetter, Marcel, de Krijger, Manon, Ponsioen, Cyriel Y, Trivedi, Palak, Hirschfield, Gideon, Schramm, Christoph, Liu, Chung Heng, Bowlus, Christopher L, Estes, Derek J, Pratt, Daniel, Hedin, Charlotte, Bergquist, Annika, de Vries, Annemarie C, van der Woude, C Janneke, Yu, Lei, Assis, David N, Boyer, James, Ytting, Henriette, Hallibasic, Emina, Trauner, Michael, Marschall, Hanns-Ulrich, Daretti, Luigi M, Marzioni, Marco, Yimam, Kidist K, Perin, Nicola, Floreani, Annarosa, Beretta-Piccoli, Benedetta Terziroli, Rogers, Jennifer K, Group, International Primary Sclerosing Cholangitis Study, and Levy, Cynthia

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Digestive Diseases - (Gallbladder), Liver Disease, Digestive Diseases, Inflammatory Bowel Disease, Autoimmune Disease, Chronic Liver Disease and Cirrhosis, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Oral and gastrointestinal, Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized, Child, Cholangitis, Sclerosing, Gastrointestinal Agents, Humans, Inflammatory Bowel Diseases, Integrins, Liver Function Tests, Middle Aged, Retrospective Studies, Young Adult, Cholestatic Liver Disease, Ulcerative Colitis, Crohn's Disease, Integrin alpha4beta7, International Primary Sclerosing Cholangitis Study Group, Crohn’s Disease, Gastroenterology & Hepatology, Clinical sciences
Abstract

Background & aimsGut-homing lymphocytes that express the integrin α4β7 and CCR9 might contribute to development of primary sclerosing cholangitis (PSC). Vedolizumab, which blocks the integrin α4β7, is used to treat patients with inflammatory bowel diseases (IBD), but there are few data on its efficacy in patients with PSC. We investigated the effects of vedolizumab in a large international cohort of patients with PSC and IBD.MethodsWe collected data from European and North American centers participating in the International PSC Study Group from patients with PSC and IBD who received at least 3 doses of vedolizumab (n = 102; median vedolizumab treatment duration, 412 days). Demographic and clinical data were collected from baseline and during the follow-up period (until liver transplantation, death, or 56 days after the final vedolizumab infusion). We analyzed overall changes in biochemical features of liver and proportions of patients with reductions in serum levels of alkaline phosphatase (ALP) of 20% or more, from baseline through last follow-up evaluation. Other endpoints included response of IBD to treatment (improved, unchanged, or worsened, judged by the treating clinician, as well as endoscopic score) and liver-related outcomes.ResultsIn the entire cohort, the median serum level of ALP increased from 1.54-fold the upper limit of normal at baseline to 1.64-fold the upper limit of normal at the last follow-up examination (P = .018); serum levels of transaminases and bilirubin also increased by a small amount between baseline and the last follow-up examination. Serum levels of ALP decreased by 20% or more in 21 patients (20.6%); only the presence of cirrhosis (odds ratio, 4.48; P = .019) was independently associated with this outcome. Of patients with available endoscopic data, 56.8% had a response of IBD to treatment. Liver-related events occurred in 21 patients (20.6%), including bacterial cholangitis, cirrhosis decompensation, or transplantation.ConclusionsIn an analysis of patients with PSC and IBD in an international study group, we found no evidence for a biochemical response to vedolizumab, although serum level of ALP decreased by 20% or more in a subset of patients. Vedolizumab appears to be well tolerated and the overall response of IBD was the same as expected for patients without PSC.

Published
2020

45. Adequate versus deep response to ursodeoxycholic acid in primary biliary cholangitis: To what extent and under what conditions is normal alkaline phosphatase level associated with complication-free survival gain?

Author

Corpechot, C, Lemoinne, S, Soret, P, Hansen, B, Hirschfield, G, Gulamhusein, A, Montano-Loza, A, Lytvyak, E, Pares, A, Olivas, I, Eaton, J, Osman, K, Schramm, C, Sebode, M, Lohse, A, Dalekos, G, Gatselis, N, Nevens, F, Cazzagon, N, Zago, A, Russo, F, Floreani, A, Abbas, N, Trivedi, P, Thorburn, D, Saffioti, F, Barkai, L, Roccarina, D, Calvaruso, V, Fichera, A, Delamarre, A, Sobenko, N, Villamil, A, Medina-Morales, E, Bonder, A, Patwardhan, V, Rigamonti, C, Carbone, M, Invernizzi, P, Cristoferi, L, Van Der Meer, A, De Veer, R, Zigmond, E, Yehezkel, E, Kremer, A, Deibel, A, Bruns, T, Grosse, K, Wetten, A, Dyson, J, Jones, D, Dumortier, J, Pageaux, G, De Ledinghen, V, Chazouilleres, O, Carrat, F, Corpechot C., Lemoinne S., Soret P. -A., Hansen B., Hirschfield G., Gulamhusein A., Montano-Loza A. J., Lytvyak E., Pares A., Olivas I., Eaton J. E., Osman K. T., Schramm C., Sebode M., Lohse A. W., Dalekos G., Gatselis N., Nevens F., Cazzagon N., Zago A., Russo F. P., Floreani A., Abbas N., Trivedi P., Thorburn D., Saffioti F., Barkai L., Roccarina D., Calvaruso V., Fichera A., Delamarre A., Sobenko N., Villamil A. M., Medina-Morales E., Bonder A., Patwardhan V., Rigamonti C., Carbone M., Invernizzi P., Cristoferi L., Van Der Meer A., De Veer R., Zigmond E., Yehezkel E., Kremer A. E., Deibel A., Bruns T., Grosse K., Wetten A., Dyson J. K., Jones D., Dumortier J., Pageaux G. -P., De Ledinghen V., Chazouilleres O., Carrat F., Corpechot, C, Lemoinne, S, Soret, P, Hansen, B, Hirschfield, G, Gulamhusein, A, Montano-Loza, A, Lytvyak, E, Pares, A, Olivas, I, Eaton, J, Osman, K, Schramm, C, Sebode, M, Lohse, A, Dalekos, G, Gatselis, N, Nevens, F, Cazzagon, N, Zago, A, Russo, F, Floreani, A, Abbas, N, Trivedi, P, Thorburn, D, Saffioti, F, Barkai, L, Roccarina, D, Calvaruso, V, Fichera, A, Delamarre, A, Sobenko, N, Villamil, A, Medina-Morales, E, Bonder, A, Patwardhan, V, Rigamonti, C, Carbone, M, Invernizzi, P, Cristoferi, L, Van Der Meer, A, De Veer, R, Zigmond, E, Yehezkel, E, Kremer, A, Deibel, A, Bruns, T, Grosse, K, Wetten, A, Dyson, J, Jones, D, Dumortier, J, Pageaux, G, De Ledinghen, V, Chazouilleres, O, Carrat, F, Corpechot C., Lemoinne S., Soret P. -A., Hansen B., Hirschfield G., Gulamhusein A., Montano-Loza A. J., Lytvyak E., Pares A., Olivas I., Eaton J. E., Osman K. T., Schramm C., Sebode M., Lohse A. W., Dalekos G., Gatselis N., Nevens F., Cazzagon N., Zago A., Russo F. P., Floreani A., Abbas N., Trivedi P., Thorburn D., Saffioti F., Barkai L., Roccarina D., Calvaruso V., Fichera A., Delamarre A., Sobenko N., Villamil A. M., Medina-Morales E., Bonder A., Patwardhan V., Rigamonti C., Carbone M., Invernizzi P., Cristoferi L., Van Der Meer A., De Veer R., Zigmond E., Yehezkel E., Kremer A. E., Deibel A., Bruns T., Grosse K., Wetten A., Dyson J. K., Jones D., Dumortier J., Pageaux G. -P., De Ledinghen V., Chazouilleres O., and Carrat F.

Abstract

Background and Aims: Normal alkaline phosphatase (ALP) levels in ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC) are associated with better long-term outcome. However, second-line therapies are currently recommended only when ALP levels remain above 1.5 times the upper limit of normal (×ULN) after 12-month UDCA. We assessed whether, in patients considered good responders to UDCA, normal ALP levels were associated with significant survival gains. Approach and Results: We performed a retrospective cohort study of 1047 patients with PBC who attained an adequate response to UDCA according to Paris-2 criteria. Time to liver-related complications, liver transplantation, or death was assessed using adjusted restricted mean survival time (RMST) analysis. The overall incidence rate of events was 17.0 (95% CI: 13.7-21.1) per 1000 out of 4763.2 patient-years. On the whole population, normal serum ALP values (but not normal gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST); or total bilirubin < 0.6 ×ULN) were associated with a significant absolute complication-free survival gain at 10 years (mean 7.6 months, 95% CI: 2.7 - 12.6 mo.; p = 0.003). In subgroup analysis, this association was significant in patients with a liver stiffness measurement ≥ 10 kPa and/or age ≤ 62 years, with a 10-year absolute complication-free survival gain of 52.8 months (95% CI: 45.7-59.9, p < 0.001) when these 2 conditions were met. Conclusions: PBC patients with an adequate response to UDCA and persistent ALP elevation between 1.1 and 1.5 ×ULN, particularly those with advanced fibrosis and/or who are sufficiently young, remain at risk of poor outcome. Further therapeutic efforts should be considered for these patients.

Published
2024

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