Endoscopic scores for inflammatory bowel disease in the era of 'mucosal healing'. old problem, new perspectives

The importance of the endoscopic evaluation in inflammatory bowel disease (IBD) management has been recognized for many years. However, the modalities for reporting endoscopic activity represent an ongoing challenge. To address this, several endoscopic scores have been proposed. Very few have been properly validated, and the use of such tools remains sub-optimal and is mainly restricted to clinical trials. In recent years, a growing emphasis of the concept of 'mucosal healing' as a prognostic marker and therapeutic goal has increased the need for a more accurate definition of endoscopic activity in both ulcerative colitis (UC) and Crohn's Disease (CD). In the present review, the evolution of the challenges related to endoscopic scores in IBD has been analyzed, with particular attention paid to the renewed relevance of endoscopic activity in recent years. Currently, despite the growing relevance of endoscopic activity, evaluating this activity in IBD is still a challenge. The implementation of efficacious endoscopic scores and a better definition of the absence of activity (mucosal healing) are needed.The importance of the endoscopic evaluation in inflammatory bowel disease (IBD) management has been recognized for many years. However, the modalities for reporting endoscopic activity represent an ongoing challenge. To address this, several endoscopic scores have been proposed. Very few have been properly validated, and the use of such tools remains sub-optimal and is mainly restricted to clinical trials. In recent years, a growing emphasis of the concept of 'mucosal healing' as a prognostic marker and therapeutic goal has increased the need for a more accurate definition of endoscopic activity in both ulcerative colitis (UC) and Crohn's Disease (CD). In the present review, the evolution of the challenges related to endoscopic scores in IBD has been analyzed, with particular attention paid to the renewed relevance of endoscopic activity in recent years. Currently, despite the growing relevance of endoscopic activity, evaluating this activity in IBD is still a challenge. The implementation of efficacious endoscopic scores and a better definition of the absence of activity (mucosal healing) are needed

Generalized Fractional Master Equation for Self-Similar Stochastic Processes Modelling Anomalous Diffusion

The Master Equation approach to model anomalous diffusion is considered. Anomalous diffusion in complex media can be described as the result of a superposition mechanism reflecting inhomogeneity and nonstationarity properties of the medium. For instance, when this superposition is applied to the time-fractional diffusion process, the resulting Master Equation emerges to be the governing equation of the Erdélyi-Kober fractional diffusion, that describes the evolution of the marginal distribution of the so-called generalized grey Brownian motion. This motion is a parametric class of stochastic processes that provides models for both fast and slow anomalous diffusion: it is made up of self-similar processes with stationary increments and depends on two real parameters. The class includes the fractional Brownian motion, the time-fractional diffusion stochastic processes, and the standard Brownian motion. In this framework, the M-Wright function (known also as Mainardi function) emerges as a natural generalization of the Gaussian distribution, recovering the same key role of the Gaussian density for the standard and the fractional Brownian motion

Two-particle anomalous diffusion: Probability density functions and self-similar stochastic processes

Two-particle dispersion is investigated in the context of anomalous diffusion. Two different modeling approaches related to time subordination are considered and unified in the framework of self-similar stochastic processes. By assuming a single-particle fractional Brownian motion and that the two-particle correlation function decreases in time with a power law, the particle relative separation density is computed for the cases with time subordination directed by a unilateral M-Wright density and by an extremal Lévy stable density. Looking for advisable mathematical properties (for instance, the stationarity of the increments), the corresponding selfsimilar stochastic processes are represented in terms of fractional Brownian motions with stochastic variance, whose profile is modelled by using the M-Wright density or the Lévy stable density

The potential role of illness expectations in the progression of medical diseases

To what extent can one's mind promote direct changes to the body? Can one's beliefs about the body become a physical reality, without mediating effects from behaviors? Specifically, can medical symptoms and the course of a disease be directly affected by a person's mindset about the illness? There is a vast literature about placebo and nocebo effects, that promote physical changes by creating the expectation of a change through a primer (for example, a fake pill). Placebos, however, often imply deception, or at least ambiguity, to be effective. The concept of Illness Expectation describes the expectations, both implicit and explicit, that a person who has received a diagnosis makes about the course of the disease. It can be characterized by different degrees of rigidity, and it is argued here that these expectations can ultimately lead to changes in the disease progression. These changes may happen through behavior modifications, or through a non-behavioral pathway, which may deserve exploration efforts from the scientific literature

A generalized Stefan model accounting for system memory and non-locality

The Stefan problem, involving the tracking of an evolving phase-change front, is the prototypical example of a moving boundary problem. In basic one- dimensional problems it is well known that the front advances as the square root of time. When memory or non-locality are introduced into the system however, this classic signal may be anomalous; replaced by a power-law advance with a time exponent that differs from n = 1/2. Up to now memory treatments in Stefan problem models have only been able to reproduce sub-diffusive front movements with exponents n 1/2. In the present paper, using a generalized Caputo fractional derivative operator, we introduce new memory and non-local treatment for Stefan problems. On considering a limit case Stefan problem, related to the melting problem, we are able to show that, this gen- eral treatment can not only produce arbitrary power-law in time predictions for the front movement but, in the case of memory treatments, can also produce non-power-law anomalous behaviors. Further, also in the context of the limit problem, we are able to establish an equivalence between non-locality and a space varying conductivity and memory and a time varying conductivity

Gaussian processes in complex media: new vistas on anomalous diffusion

Normal or Brownian diffusion is historically identified by the linear growth in time of the variance and by a Gaussian shape of the displacement distribution. Processes departing from the at least one of the above conditions defines anomalous diffusion, thus a nonlinear growth in time of the variance and/or a non-Gaussian displacement distribution. Motivated by the idea that anomalous diffusion emerges from standard diffusion when it occurs in a complex medium, we discuss a number of anomalous diffusion models for strongly heterogeneous systems. These models are based on Gaussian processes and characterized by a population of scales, population that takes into account the medium heterogeneity. In particular, we discuss diffusion processes whose probability density function solves space- and time-fractional diffusion equations through a proper population of time-scales or a proper population of length-scales. The considered modeling approaches are: the continuous time random walk, the generalized gray Brownian motion, and the time-subordinated process. The results show that the same fractional diffusion follows from different populations when different Gaussian processes are considered. The different populations have the common feature of a large spreading in the scale values, related to power-law decay in the distribution of population itself. This suggests the key role of medium properties, embodied in the population of scales, in the determination of the proper stochastic process underlying the given heterogeneous medium.This research was supported by the Basque Government through the BERC 2014–2017 and BERC 2018–2021 programs, and by the Spanish Ministry of Economy and Competitiveness MINECO through BCAM Severo Ochoa excellence accreditations SEV- 2013-0323 and SEV-2017-0718 and through project MTM2016- 76016-R MI

Random diffusivity from stochastic equations: comparison of two models for Brownian yet non-Gaussian diffusion

A considerable number of systems have recently been reported in which Brownian yet non-Gaussian dynamics was observed. These are processes characterised by a linear growth in time of the mean squared displacement, yet the probability density function of the particle displacement is distinctly non-Gaussian, and often of exponential (Laplace) shape. This apparently ubiquitous behaviour observed in very different physical systems has been interpreted as resulting from diffusion in inhomogeneous environments and mathematically represented through a variable, stochastic diffusion coefficient. Indeed different models describing a fluctuating diffusivity have been studied. Here we present a new view of the stochastic basis describing time-dependent random diffusivities within a broad spectrum of distributions. Concretely, our study is based on the very generic class of the generalised Gamma distribution. Two models for the particle spreading in such random diffusivity settings are studied. The first belongs to the class of generalised grey Brownian motion while the second follows from the idea of diffusing diffusivities. The two processes exhibit significant characteristics which reproduce experimental results from different biological and physical systems. We promote these two physical models for the description of stochastic particle motion in complex environments.the DFG within project ME 1535/6-

Discretizations of the spectral fractional Laplacian on general domains with Dirichlet, Neumann, and Robin boundary conditions

In this work, we propose novel discretisations of the spectral fractional Laplacian on bounded domains based on the integral formulation of the operator via the heat-semigroup formalism. Specifically, we combine suitable quadrature formulas of the integral with a finite element method for the approximation of the solution of the corresponding heat equation. We derive two families of discretisations with order of convergence depending on the regularity of the domain and the function on which the fractional Laplacian is acting. Unlike other existing approaches in literature, our method does not require the computation of the eigenpairs of the Laplacian on the considered domain, can be implemented on possibly irregular bounded domains, and can naturally handle different types of boundary constraints. Various numerical simulations are provided to illustrate performance of the proposed method and support our theoretical results.FdT acknowledges support of Toppforsk project Waves and Nonlinear Phenomena (WaNP), grant no. 250070 from the Research Council of Norway. ERCIM ``Alain Benoussan" Fellowship programm

Detection of bovine papillomavirus type 2 in the peripheral blood of cattle with urinary bladder tumours: possible biological role

Bovine papillomavirus type 2 (BPV-2) infection has been associated with urinary bladder tumours in adult cattle grazing on bracken fern-infested land. In this study, we investigated the simultaneous presence of BPV-2 in whole blood and urinary bladder tumours of adult cattle in an attempt to better understand the biological role of circulating BPV-2. Peripheral blood samples were collected from 78 cattle clinically suffering from a severe chronic enzootic haematuria. Circulating BPV-2 DNA was detected in 61 of them and in two blood samples from healthy cows. Fifty of the affected animals were slaughtered at public slaughterhouses and neoplastic proliferations in the urinary bladder were detected in all of them. BPV-2 DNA was amplified and sequenced in 78% of urinary bladder tumour samples and in 38.9% of normal samples as a control. Circulating episomal BPV-2 DNA was detected in 78.2% of the blood samples. Simultaneous presence of BPV-2 DNA in neoplastic bladder and blood samples was detected in 37 animals. Specific viral E5 mRNA and E5 oncoprotein were also detected in blood by RT-PCR and Western blot/immunocytochemistry, respectively. It is likely that BPV-2 can persist and be maintained in an active status in the bloodstream, in particular in the lymphocytes, as a reservoir of viral infection that, in the presence of co-carcinogens, may cause the development of urinary bladder tumours

Application of clinical indexes in ulcerative colitis patients in regular follow-up visit. correlation with endoscopic 'mucosal healing' and implication for management

OBJECTIVE: Ulcerative Colitis (UC) is a chronic inflammatory disease of the colon of unknown etiology. Several clinical indexes have been proposed for UC disease activity evaluation, but none have been properly validated. Moreover, the reference parameter for the scores and their prognostic value is not clear. Mucosal healing has been recently proposed as an important end-point. Aim of the present study was to evaluate the correlation of four clinical indexes with objective diagnostic tools for UC evaluation, the discriminative ability in identifying patients with endoscopic mucosal healing, and to analyze the possible prognostic indication for disease course in 1 year of follow-up. PATIENTS AND METHODS: We analyzed data of 75 patients recorded in regular follow-up visit in IBD clinic at S. Andrea Hospital, Rome, between 2007-2011. We recorded clinical data and lab tests at the time of the visit, and endoscopic/ histological repor ts performed within 1 month. Clinical indexes (Seo' activity index, Simple Clinical Colitis Activity Index, partial Mayo score and Endoscopic-Clinical Correlation Index) were calculated and correlation to endoscopic and histologic activity, and to C-reactive protein increment, was assessed by mean of Spearman's rank correlation. Discriminative ability of the indexes for patients with and without endoscopic mucosal healing was tested by calculation of area under ROC curve (AUC). Patients with low and high clinical scores were compared for number of flares and increment of therapy during 1 year of follow-up. RESULTS: Clinical indexes had a good correlation with endoscopic activity (mean r = 0.73 ± 0.06), a fair correlation with CRP-increment (mean r = 0.55 ± 0.01) and a poor one with histologic activity (mean r = 0.35 ± 0.01). The discriminatory ability of the indexes for endoscopic mucosal healing was good for all the indexes (mean AUC = 0.87 ± 0.05). Patients with high clinical score had more flares and required more frequently increase of therapy at 1 year of follow up compared with patients with low score. CONCLUSIONS: Clinical indexes have a good correlation with endoscopic activity and can discriminate patients with and without mucosal healing. Patients with low and high score have different risk of disease flare and of need to increase therapy at 1 year. Clinical indexes may represent a useful tool for disease assessment in clinical practice in UC outpatients with mildmoderate disease