HiPhomε\varepsilon -: HIgh order Projection-based HOMogenisation for advection diffusion reaction problems

We propose a new model reduction technique for multiscale scalar transport problems that exhibit dominant axial dynamics. To this aim, we rely on the separation of variables to combine a Hierarchical Model (HiMod) reduction with a two-scale asymptotic expansion. We extend the two-scale asymptotic expansion to an arbitrary order and exploit the high-order correctors to define the HiMod modal basis, which approximates the transverse dynamics of the flow, while we adopt a finite element discretisation to model the leading stream. The resulting method, which is named HiPhom$\varepsilon$ (HIgh-order Projection-based HOMogEnisation), is successfully assessed both in steady and unsteady advection-diffusion-reaction settings. The numerical results confirm the very good performance of HiPhom$\varepsilon$, which improves the accuracy and the convergence rate of HiMod and extends the reliability of the standard homogenised solution to transient and pre-asymptotic regimes

Automatic tailoring of the lowest PEEP to abolish tidal expiratory flow limitation in seated and supine COPD patients

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Characterization of upper limb use in health care workers during regular shifts: A quantitative approach based on wrist-worn accelerometers

Despite the high prevalence of upper limb (UL) work-related musculoskeletal disorders (WRMSD) among health care workers (HCWs), little is known about their relationship with exposure to biomechanical risk factors. This study aimed to assess UL activity features under actual working conditions using two wrist-worn accelerometers. Accelerometric data were processed to obtain duration, intensity, and asymmetry of UL use in 32 HCWs during the execution of commonly performed tasks (e.g., patient hygiene, transfer, and meal distribution) within a regular shift. The results show that such tasks are characterized by significantly different patterns of UL use, in particular, higher intensities and larger asymmetries were observed respectively for patient hygiene and meal distribution. The proposed approach appears, thus, suitable to discriminate tasks characterized by different UL motion patterns. Future studies could benefit from the integration of such measures with self-reported workers’ perception to elucidate the relationship between dynamic UL movements and WRMSD

Management of targeted therapies in cancer patients with chronic kidney disease, or on haemodialysis: An Associazione Italiana di Oncologia Medica (AIOM)/Societa' Italiana di Nefrologia (SIN) multidisciplinary consensus position paper

Abstract The increasing availability of novel biological anticancer agents has greatly improved the outcome of several cancer patients; unfortunately, data regarding efficacy, safety and pharmacokinetics of many of these agents in patients with chronic renal disease or on hemodialysis are scanty. Furthermore these results are controversial and a treatment strategy has not yet been established. Therefore, the Associazione Italiana di Oncologia Medica and the Societa italiana di Nefrologia undertook the present work aiming at providing health professionals with a tool for easier clinical management of target therapies in this setting of patients. A web-based search of MEDLINE/PubMed library data published from 2000 to June 2018 has been performed. More than one hundred papers, including recommendations and expert opinions, were selected and discussed by the authors. A panel of experts provided additional biological and clinical information, helping in clarifying some issues in the absence of clear-cut information from the literature

Enhanced p53 Levels Are Involved in the Reduced Mineralization Capacity of Osteoblasts Derived from Shwachman–Diamond Syndrome Subjects

14noopenShwachman–Diamond syndrome (SDS) is a rare autosomal recessive disorder characterized by bone marrow failure, exocrine pancreatic insufficiency, and skeletal abnormalities, caused by loss-of-function mutations in the SBDS gene, a factor involved in ribosome biogenesis. By analyzing osteoblasts from SDS patients (SDS-OBs), we show that SDS-OBs displayed reduced SBDS gene expression and reduced/undetectable SBDS protein compared to osteoblasts from healthy subjects (H-OBs). SDS-OBs cultured in an osteogenic medium displayed a lower mineralization capacity compared to H-OBs. Whole transcriptome analysis showed significant differences in the gene expression of SDS-OBs vs. H-OBs, particularly in the ossification pathway. SDS OBs expressed lower levels of the main genes responsible for osteoblastogenesis. Of all downregulated genes, Western blot analyses confirmed lower levels of alkaline phosphatase and collagen type I in SDS-OBs than in H-OBs. Interestingly, SDS-OBs showed higher protein levels of p53, an inhibitor of osteogenesis, compared to H-OBs. Silencing of Tp53 was associated with higher collagen type I and alkaline phosphatase protein levels and an increase in SDS-OB mineralization capacity. In conclusion, our results show that the reduced capacity of SDS-OBs to mineralize is mediated, at least in part, by the high levels of p53 and highlight an important role of SBDS in osteoblast functions.openFrattini, Annalisa; Bolamperti, Simona; Valli, Roberto; Cipolli, Marco; Pinto, Rita Maria; Bergami, Elena; Frau, Maria Rita; Cesaro, Simone; Signo, Michela; Bezzerri, Valentino; Porta, Giovanni; Khan, Abdul Waheed; Rubinacci, Alessandro; Villa, IsabellaFrattini, Annalisa; Bolamperti, Simona; Valli, Roberto; Cipolli, Marco; Pinto, Rita Maria; Bergami, Elena; Frau, Maria Rita; Cesaro, Simone; Signo, Michela; Bezzerri, Valentino; Porta, Giovanni; Khan, Abdul Waheed; Rubinacci, Alessandro; Villa, Isabell

Vitreous Substitutes: The Present and the Future

Vitreoretinal surgery has advanced in numerous directions during recent years. The removal of the vitreous body is one of the main characteristics of this surgical procedure. Several molecules have been tested in the past to fill the vitreous cavity and to mimic its functions. We here review the currently available vitreous substitutes, focusing on their molecular properties and functions, together with their adverse effects. Afterwards we describe the characteristics of the ideal vitreous substitute. The challenges facing every ophthalmology researcher are to reach a long-term intraocular permanence of vitreous substitute with total inertness of the molecule injected and the control of inflammatory reactions. We report new polymers with gelification characteristics and smart hydrogels representing the future of vitreoretinal surgery. Finally, we describe the current studies on vitreous regeneration and cell cultures to create new intraocular gels with optimal biocompatibility and rheological properties

Impact of space-time mesh adaptation on solute transport modeling in porous media

open4siWe implement a space-time grid adaptation procedure to efficiently improve the accuracy of numerical simulations of solute transport in porous media in the context of model parameter estimation. We focus on the Advection Dispersion Equation (ADE) for the interpretation of non-reactive transport experiments in laboratory-scale heterogeneous porous media. When compared to a numerical approximation based on a fixed space-time discretization, our approach is grounded on a joint automatic selection of the spatial grid and the time step to capture the main (space-time) system dynamics. Spatial mesh adaptation is driven by an anisotropic recovery-based error estimator which enables us to properly select the size, shape and orientation of the mesh elements. Adaptation of the time step is performed through an ad-hoc local reconstruction of the temporal derivative of the solution via a recovery-based approach. The impact of the proposed adaptation strategy on the ability to provide reliable estimates of the key parameters of an ADE model is assessed on the basis of experimental solute breakthrough data measured following tracer injection in a non-uniform porous system. Model calibration is performed in a Maximum Likelihood (ML) framework upon relying on the representation of the ADE solution through a generalized Polynomial Chaos Expansion (gPCE). Our results show that the proposed anisotropic space-time grid adaptation leads to ML parameter estimates and to model results of markedly improved quality when compared to classical inversion approaches based on a uniform space-time discretization.openEsfandiar, B; Porta, G; Perotto, S; Guadagnini, AESFANDIAR JAHROMI, Bahman; Porta, GIOVANNI MICHELE; Perotto, Simona; Guadagnini, Albert

Long-term treatment over 52 weeks with monthly fremanezumab in drug-resistant migraine. A prospective multicenter cohort study

Background: Real-world studies on fremanezumab, an anti-calcitonin gene-related peptide monoclonal antibody for migraine prevention, are few and with limited follow-up. Objective: We aimed to evaluate the long-term (up to 52 weeks) effectiveness and tolerability of fremanezumab in high-frequency episodic migraine and chronic migraine. Methods: This s an independent, prospective, multicenter cohort study enrolling outpatients in 17 Italian Headache Centers with high-frequency episodic migraine or chronic migraine and multiple preventive treatment failures. Patients were treated with fremanezumab 225 mg monthly. The primary outcomes included changes from baseline (1 month before treatment) in monthly headache days, response rates (reduction in monthly headache days from baseline), and persistence in medication overuse at months 3, 6, and 12 (all outcome timeframes refer to the stated month). Secondary outcomes included changes from baseline in acute medication intake and disability questionnaires scores at the same timepoints. A last observation carried forward analysis was also performed. Results: A total of 90 patients who received at least one dose of fremanezumab and with a potential 12-month follow-up were included. Among them, 15 (18.0%) patients discontinued treatment for the entire population, a reduction in monthly headache days compared with baseline was reported at month 3, with a significant median [interquartile range] reduction in monthly headache days (− 9.0 [11.5], p < 0.001). A statistically different reduction was also reported at month 6 compared with baseline (− 10.0 [12.0]; p < 0.001) and at 12 months of treatment (− 10.0 [14.0]; p < 0.001). The percentage of patients with medication overuse was significantly reduced compared with baseline from 68.7% (57/83) to 29.6% (24/81), 25.3% (19/75), and 14.7% (10/68) at 3, 6, and 12 months of treatment, respectively (p < 0.001). Acute medication use (days and total number) and disability scores were also significantly reduced (p < 0.001). A ≥ 50% response rate was achieved for 51.9, 67.9, and 76.5% of all patients at 3, 6, and 12 months, respectively. Last observation carried forward analyses confirmed these findings. Fremanezumab was well tolerated, with just one patient discontinuing treatment because of adverse events. Conclusions: This study provides evidence for the real-world effectiveness of fremanezumab in treating both high-frequency episodic migraine and chronic migraine, with meaningful and sustained improvements in multiple migraine-related variables. No new safety issue was identified