First feasibility demonstration of GNSS-seismology for anthropogenic earthquakes detection.

High-rate GNSS has been proven effective in characterising waveforms and co-seismic displacements due to medium-to-strong natural earthquakes. No application focused on small magnitude events like shallow anthropogenic earthquakes, where displacements and noise have the same order of magnitude. We propose a procedure based on proper signal detection and filtering of the position and velocity time series obtained from high-rate (10 Hz) GNSS data processing with two intrinsically different approaches (Precise Point Positioning and variometry). We tested it on five mining tremors with magnitudes of 3.4-4.0, looking both at event detection and its kinematic characterisation. Here we show a high agreement, at the level of 1 s, between GNSS and seismic solutions for the earthquake first epoch detection. Also, we show that high-rate multi-constellation (GPS + Galileo) GNSS can reliably characterise low-magnitude shallow earthquakes in terms of induced displacements and velocities, and, including their peak values, respectively, at the level of very few millimetres and 1-2 cm/s, paving the way to the routine use of GNSS-seismology for monitoring human activities prone to cause small earthquakes and related potential damages.

GNSS total variometric approach: first demonstration of a tool for real-time tsunami genesis estimation.

Global Navigation Satellite System (GNSS) is used in seismology to study the ground displacements as well as to monitor the ionospheric total electron content (TEC) perturbations following seismic events. The aim of this work is to combine these two observations in one real-time method based on the Total Variometric Approach (TVA) to include the GNSS real-time data stream in future warning systems and tsunami genesis estimation observing both, ground motion and TEC. Our TVA couples together the Variometric Approach for Displacement Analysis Stand-alone Engine (VADASE) with the Variometric Approach for Real-Time Ionosphere Observation (VARION) algorithms. We apply the TVA to the Mw 8.3 Illapel earthquake, that occurred in Chile on September 16, 2015, and we demonstrate the coherence of the earthquake ground shaking and the TEC perturbation by using the same GNSS data stream in a real-time scenario. Nominally, we also highlight a stronger kinetic energy released in the north of the epicenter and visible in both, the ground motion and the TEC perturbation detect at 30 s and around 9.5 min after the rupture respectively. The high spatial resolution of ionospheric TEC measurement seems to match with the extent of the seismic source. The GNSS data stream by TVA of both the ground and ionospheric measurement opens today new perspectives to real-time warning systems for tsunami genesis estimation.

Appropriateness of proton pump inhibitors treatment in clinical practice: Prospective evaluation in outpatients and perspective assessment of drug optimisation.

BACKGROUND: High rates of inappropriate proton pump inhibitor (PPI) prescriptions have been reported in retrospective database analyses. Assessing the appropriateness of long-term PPIs in outpatients, with a proactive approach at drug optimisation may enhance treatment adequacy. AIMS: To describe the characteristics of outpatients who are on long-term PPIs, to assess the magnitude of inappropriate PPI prescriptions, and to evaluate the rate of drug optimisation following specialist recommendations. METHODS: Appropriateness of long-term (>8weeks) PPI prescription was prospectively assessed in 249 consecutive patients referred to a Gastroenterology outpatient clinic. We recorded reason for prescription, dose, modality, duration of therapy, and attempts at PPI optimisation. RESULTS: PPIs were inappropriately prescribed in 96/249 patients (38.6%). Gastro-oesophageal reflux disease (50/143, 35.0%) and prophylaxis of anti-platelet/non-steroidal anti-inflammatory drugs (5/49, 10.2%) were the most common PPI indications and those with the lowest rate of inappropriateness, while the highest rates were observed for treatment of dyspepsia (10/12, 83.3%) and anti-coagulant therapy (21/21, 100%). PPI treatment was optimised in 112 patients (45.0%). CONCLUSIONS: PPIs are inappropriately used in about 40% of outpatients, reflecting scant attention to guidelines. A proactive approach may improve therapeutic adequacy in approximately half of patients. Educational efforts to guide PPI prescription should be further pursued.

Course of oesophageal varices and performance of noninvasive predictors following Hepatitis C Virus clearance in compensated advanced chronic liver disease.

BACKGROUND: In patients with hepatitis C virus (HCV) and compensated advanced chronic liver disease (cACLD), there is evidence that sustained virological response (SVR) to direct-acting antivirals (DAA) may ameliorate portal hypertension, although both the course of oesophageal varices and the performance of their noninvasive predictors following DAA-induced SVR are less defined. In this study, our aim was to assess the variation in oesophageal varices status in HCV patients with cACLD who obtained an SVR to DAAs and to evaluate the diagnostic performance of noninvasive predictors of varices after HCV cure. MATERIAL AND METHODS: Sixty-three HCV patients with cACLD and SVR to DAAs were prospectively followed up, and oesophageal varices surveillance was carried out according to the Baveno VI indications. Appearance and disappearance of varices, accuracy performance of their noninvasive predictors (Baveno/expanded Baveno VI criteria, platelet count/spleen diameter ratio) and number of endoscopies spared with their application were calculated. RESULTS: Following SVR, varices developed or disappeared in 12.1% and 17.4% of patients, respectively. The negative predictive value for varices of the Baveno VI, expanded Baveno VI criteria and platelet count/spleen diameter ratio following SVR was 88.2% (65.6-96.7), 83.3% (66.3-92.7) and 80.7% (67.1-89.5), respectively. Their application would have saved 30.4%, 42.9% and 55.4% of endoscopies, with no varices needing treatment missed using both Baveno VI criteria. CONCLUSIONS: In HCV patients with cACLD, following SVR to DAA, the expanded Baveno VI criteria provide the best balance between utility (diagnostic accuracy and endoscopies avoided) and safety (varices needing treatment missed) for varices surveillance.

Strictures in Crohn's Disease: From Pathophysiology to Treatment.

Despite recent advances aimed to treat transmural inflammation in Crohn's disease (CD) patients, the progression to a structuring behavior still represents an issue for clinicians. As inflammation becomes chronic and severe, the attempt to repair damaged tissue can result in an excessive production of extracellular matrix components and deposition of connective tissue, thus favoring the formation of strictures. No specific and accurate clinical predictors or diagnostic tools for intestinal fibrosis exist, and to date, no genetic or serological marker is in routine clinical use. Therefore, intestinal fibrosis is usually diagnosed when it becomes clinically evident and strictures have already occurred. Anti-fibrotic agents such as tranilast, peroxisome proliferator-activated receptor gamma agonists, rho kinase inhibitors, and especially mesenchymal stem cell therapy have provided interesting results, but most of the evidence has been derived from studies performed in vitro. Therefore, current therapy of fibrotic strictures relies mainly on endoscopic and surgical procedures. Although its long-term outcomes may be debated, endoscopic balloon dilation appears to be the safest and most effective approach to treat appropriately selected strictures. The use of endoscopic stricturotomy is currently limited by the expertise needed to perform it and by the few data available in the literature. Some good results have been achieved by the positioning of self-expandable metal stents (SEMS). However, there is no concordance regarding the type of stent to use and for how long it should be left in place. The development of new specific SEMS may lead to better outcomes and to an increased use of this alternative in CD-related strictures.

py2DIC: A New Free and Open Source Software for Displacement and Strain Measurements in the Field of Experimental Mechanics.

Thanks to the advances in computer power, memory storage and the availability of low-cost and high resolution digital cameras, Digital Image Correlation (DIC) is currently one of the most used optical and non-contact techniques for measuring material deformations. A free and open source 2D DIC software, named py2DIC, was developed at the Geodesy and Geomatics Division of the Sapienza University of Rome. Implemented in Python, the software is based on the template matching method and computes the 2D displacements and strains of samples subjected to mechanical loading. In this work, the potentialities of py2DIC were evaluated by processing two different sets of experimental data and comparing the results with other three well known DIC software packages Ncorr, Vic-2D and DICe. Moreover, an accuracy assessment was performed comparing the results with the values independently measured by a strain gauge fixed on one of the samples. The results demonstrate the possibility of successfully characterizing the deformation mechanism of the investigated materials, highlighting the pros and cons of each software package.

A randomized, 6-wk trial of a low FODMAP diet in patients with inflammatory bowel disease.

OBJECTIVE: The aim of this study was to assess the safety and efficacy of a low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet (LFD) in patients with inflammatory bowel disease (IBD). METHODS: An LFD is associated with symptom improvement in patients with functional intestinal disorders, although its safety and efficacy has not been characterized in patients with IBD. Fifty-five patients with IBD in remission or with mild disease activity were randomized to a 6-wk LFD or standard diet (SD). Disease activity (Harvey-Bradshaw index [HBi], partial Mayo score), fecal calprotectin, and disease-specific quality of life (IBD-Q) were assessed at baseline and at the end of dietary intervention. RESULTS: After the 6-wk dietary intervention, median HBi decreased in the LFD (4; IQR, 3-5 versus 3; IQR, 2-3; P = 0.024) but not in the SD (3; IQR, 3-3 versus 3; IQR, 2-4), whereas Mayo scores were numerically decreased in the LFD group and unmodified in the SD group. Median calprotectin decreased in the LFD (76.6 mg/kg; IQR, 50-286.3 versus 50 mg/kg; IQR, 50.6-81; P = 0.004) but not in the SD group (91 mg/kg; IQR, 50.6-143.6 versus 87 mg/kg; IQR, 50-235.6). Lastly, we observed a barely significant increase in median IBD-Q in the LFD group (166; IQR, 139-182 versus 177; IQR, 155-188; P = 0.05) and no modification in the SD group (181; IQR, 153-197 versus 166; IQR, 153-200). CONCLUSIONS: A short-term, LFD is safe for patients with IBD, and is associated with an amelioration of fecal inflammatory markers and quality of life even in patients with mainly quiescent disease.

Estimation of Wave Characteristics Based on Global Navigation Satellite System Data Installed on Board Sailboats.

This paper illustrates a methodology to get a reliable estimation of the local wave properties, based on the reconstruction of the motion of a moving sailboat by means of GNSS receivers installed on board and an original kinematic positioning approach. The wave parameters reconstruction may be used for many useful practical purposes, e.g. to improve of autopilots, for real-time control systems of ships, to analyze and improve the performance of race sailboats, and to estimate the local properties of the waves. A Class 40 oceanic vessel (ECO40) left from the port of "Riva di Traiano" located close to Rome (Italy) on 19 October 2014 to perform a non-stop sailing alone around the world in energy and food self-sufficiency. The proposed system was installed on ECO40 and the proposed method was applied to estimate the wave properties during a storm in the Western Mediterranean Sea. The results compared against two sets of hindcast data and wave buoy records demonstrated the reliability of the method.

Improvement in hepatitis C virus patients with advanced, compensated liver disease after sustained virological response to direct acting antivirals.

BACKGROUND: The outcome of patients with chronic hepatitis C virus infection (HCV) and advanced, compensated liver disease after sustained virological response (SVR) to direct-acting antivirals (DAAs) has not yet been completely depicted. We aimed to assess the clinical, biochemical and instrumental outcome of patients with advanced, compensated chronic HCV-related liver disease with DAA-induced SVR to DAAs and who had at least 1-year follow-up. MATERIALS AND METHODS: Fifty-two patients with cirrhosis (n = 27) and fibrosis stage F3 (n = 25) followed up for a median of 60 weeks after successful DAA treatment were included. Laboratory work-up, including APRI and FIB-4 scores, liver transient elastography and measurement of the spleen bi-polar diameter were carried out before treatment and at the end of follow-up. RESULTS: Liver stiffness decreased (P < 0.0001) from a median baseline of 15.2 kPa (12.0-20.0) to 9.3 kPa (7.5-12.0) at follow-up. A liver stiffness value suggestive of the presence (ie, ≥21.0 kPa) of clinically significant portal hypertension was found in 13 patients (25.0%) at baseline and in seven patients (13.5%) at follow-up (P = 0.037). Both APRI (P < 0.0001) and FIB-4 score (P = 0.025) progressively decreased, while platelet count increased (143 × 109 /L [117-176] to 153 × 109 /L [139-186], P = 0.003), and spleen bi-polar diameter decreased (120 mm [112-123] to 110 mm [102-116], P = 0.0009) from baseline to the end of follow-up. CONCLUSIONS: In patients advanced, compensated chronic liver disease, liver stiffness significantly improves in the long-term after SVR, and this improvement is accompanied by an amelioration of indirect indices of liver fibrosis and function, and by a decrease in parameters of portal hypertension.

Reduction in TIMP-2 serum levels predicts remission of inflammatory bowel diseases.

BACKGROUND: Growing evidence indicates tissue inhibitors of matrix metalloproteinases (TIMPs) as potential players in inflammatory bowel disease (IBD), but, no prospective data are available in IBD remission/relapse. MATERIAL & METHODS: In this prospective pilot study, a cohort of IBD patients (n = 32) was enrolled and treated with monoclonal anti-TNF-α antibodies. Patients were clinically followed up for a median period of 54 weeks. Serum circulating levels of C-reactive protein (CRP), TIMP-1 and -2, matrix metalloproteinase (MMP)-9 and -8, myeloperoxidase (MPO) and neutrophil elastase (NE) were assessed by ELISA at enrolment and at the end of the treatment. RESULTS: The percentage (%) TIMP-2 reduction from baseline to end of treatment was independently associated with IBD remission at the end of treatment and follow-up as well. ROC curve analysis further confirmed the good prognostic accuracy of % TIMP-2 reduction over the treatment period. Conversely, no other change in inflammatory molecule concentrations was able to predict short- or long-term IBD remission. CONCLUSIONS: This study indicates TIMP-2 reduction during IBD treatment with monoclonal anti-TNF-α antibodies as a potential prognostic parameter of short and long term remission. To understand if TIMP-2 is an innocent biomarker or an active pathophysiological factor in IBD remains to be clarified.

Covered versus uncovered self-expandable metal stent for palliation of primary malignant extrahepatic biliary strictures: a randomized multicenter study.

BACKGROUND AND AIMS: Self-expandable metal stents (SEMSs) are used to relieve malignant biliary obstructions. We aimed to compare stent patency, the adverse events rate, and overall survival of covered versus uncovered self-conformable metal stents in patients with primary malignant extrahepatic biliary strictures, not eligible for surgery. METHODS: This is a multicenter randomized trial analyzing 158 patients with inoperable distal malignant biliary obstruction conducted in 5 Italian referral centers between December 2014 and October 2016. Seventy-eight patients were randomized to receive a fully covered SEMS (FCSEMS), and 80 patients received uncovered SEMSs (USEMSs). Data from 148 (72 FCSEMSs and 76 USEMSs) of 158 patients were analyzed. RESULTS: Median time of stent patency was lower for FCSEMSs (240 days vs 541 days for USEMSs; P = .031). Adverse events occurred with 19 FCSEMSs (26.4%) and 10 USEMSs (13.2%); P = .061. The main causes of FCSEMS dysfunction were migration (7% vs 0% in the USEMS group) and early occlusion mainly because of sludge or overgrowth; late stent occlusion because of tumor ingrowth occurred in 13.2% of patients in the USEMS group. There were no significant differences either in levels of conjugated bilirubin improvement or in overall survival between the FCSEMS and USEMS groups. Median survival was 134 days in the FCSEMS group and 112 days in the USEMS group (P = .23). CONCLUSION: The number of stent-related adverse events was higher, although not significantly, among patients in the FCSEMS group. FCSEMSs had a significantly higher rate of migration than USEMSs, and stent occlusion occurred earlier. A significant difference in the patency rate was observed in favor of the USEMS group. (Clinical trial registration number: NCT02102984.).

Improvement in Waldenström's Macroglobulinemia after Successful Treatment of HCV with Direct-acting Antivirals.

Chronic hepatitis C (HCV) virus infection may be associated with several non-hepatic manifestations, mainly driven by chronic immune stimulation, such as mixed cryoglobulinemia and Non-Hodgkin's Lymphoma. This association has been proved by several meta-analyses and some interventional studies demonstrating that antiviral treatment may be effective in inducing HCV-associated lymphoma regression. The recent advent of direct acting antivirals (DAAs) in the therapeutic armamentarium of HCV infection made possible treatment of patients with advanced liver disease. Here we report on a rare association of a cirrhotic patient with HCV and Waldenström's Macroglobulinemia with severe cryoglobulinemia, who had already failed an interferon-based antiviral regimen, whose haematologic disease was ameliorated by HCV eradication following treatment with sofosbuvir and simeprevir with ribavirin, and where successful treatment was accompanied also by consistent improvement in liver function and parameters of portal hypertension.

Real-Time Detection of Tsunami Ionospheric Disturbances with a Stand-Alone GNSS Receiver: A Preliminary Feasibility Demonstration.

It is well known that tsunamis can produce gravity waves that propagate up to the ionosphere generating disturbed electron densities in the E and F regions. These ionospheric disturbances can be studied in detail using ionospheric total electron content (TEC) measurements collected by continuously operating ground-based receivers from the Global Navigation Satellite Systems (GNSS). Here, we present results using a new approach, named VARION (Variometric Approach for Real-Time Ionosphere Observation), and estimate slant TEC (sTEC) variations in a real-time scenario. Using the VARION algorithm we compute TEC variations at 56 GPS receivers in Hawaii as induced by the 2012 Haida Gwaii tsunami event. We observe TEC perturbations with amplitudes of up to 0.25 TEC units and traveling ionospheric perturbations (TIDs) moving away from the earthquake epicenter at an approximate speed of 316 m/s. We perform a wavelet analysis to analyze localized variations of power in the TEC time series and we find perturbation periods consistent with a tsunami typical deep ocean period. Finally, we present comparisons with the real-time tsunami MOST (Method of Splitting Tsunami) model produced by the NOAA Center for Tsunami Research and we observe variations in TEC that correlate in time and space with the tsunami waves.

A procedure for high resolution satellite imagery quality assessment.

Data products generated from High Resolution Satellite Imagery (HRSI) are routinely evaluated during the so-called in-orbit test period, in order to verify if their quality fits the desired features and, if necessary, to obtain the image correction parameters to be used at the ground processing center. Nevertheless, it is often useful to have tools to evaluate image quality also at the final user level. Image quality is defined by some parameters, such as the radiometric resolution and its accuracy, represented by the noise level, and the geometric resolution and sharpness, described by the Modulation Transfer Function (MTF). This paper proposes a procedure to evaluate these image quality parameters; the procedure was implemented in a suitable software and tested on high resolution imagery acquired by the QuickBird, WorldView-1 and Cartosat-1 satellites.