EFFICACY AND SAFETY OF BOCEPREVIR-BASED THERAPY IN HCVG1 TREATMENT-EXPERIENCED PATIENTS WITH ADVANCED FIBROSIS/CIRRHOSIS: THE ITALIAN AND SPANISH NPP EARLY ACCESS PROGRAM

Background and Aims: To maximize cost/efficay of boceprevirbased triple therapy (BOC) in patients with HCV-related advanced fibrosis/cirrhosis. Methods: ITT SVR12, safety and futility rules value were evaluated in the multicenter national Italian and Spanish early access Name- Patient-Program which includes treatment-experienced patients with HCVG1-related advanced fibrosis/cirrhosis (Metavir F3/4) treated with BOC in both countries. Results: 402 patients (mean age 55 years; range 22–75), 316 (78.6%) G1b, 255 (63.4%) F4, 60 (30.9%) with oesophageal varices, 137 (34.1%) relapsers, 95 (23.6%) partial and 168 (41.8%) null responders were enrolled. Platelets count <100,000 and albumin levels <3.5 g/dl were present in 49 (12.2%) and 22 (6.3%) patients, respectively. 369 (91.8%) received at least 1 dose of BOC. Overall ITT SVR12 rates and according to prior response to P/R, fibrosis stage and TW8 HCV-RNA value to P/R/BOC are reported in the table. At multivariate analysis, the strongest predictors of SVR12 were TW8 HCV-RNA undetectability (RR, 30.8; 95% CI, 8.7–108.7) and HCV-RNA detectable but <1000 IU/mL (RR, 9.1; 95% CI, 2.6–31.8) compared to those with HCV-RNA ≥1000 IU/mL. Two patients (0.5%) died from multi-organ failure, 13 (3.2%) developed hepatic decompensation, 41 (10.2%) had severe anemia (<8.5 g/dl) and 31 (7.7%) required at least one blood transfusion. Conclusions: In treatment-experienced patients with advanced fibrosis/cirrhosis, SVR12 attained by BOC was satisfactory. Mortality, life-threatening adverse events and severe anemia rates were similar to those reported in other real-practice studies. A TW8 futility rule enables a safely discontinuation of BOC in patients who are extremely unlikely to achieve SVR, thus optimizing the effectiveness of treatment in this difficult-to-cure population

Air-coupled transducers based on 1-3 connectivity single crystal piezocomposites

Air-coupled piezoelectric transducers made of 1-3 connectivity PMN-PT single crystal composites (centre frequency around 1.0 MHz) were designed, built and characterized. Several matching layers configurations have been tested in order to achieve optimum sensitivity or bandwidth or both. Results are compared with those obtained from similar transducers made using 1-3 PZT ceramic piezocomposites. Both kinds of transducers exhibit similar peak sensitivities (-23 dB), but single crystal transducers present a smoother and wider frequency band (up to 89%). 2012 IEEE

Ultrasonic online monitoring of the ham salting process. Methods for signal analysis: Time of flight calculation

[EN] In the dry-cured ham industry, an accurate control of the dry-salting process is especially complex because of the great heterogeneity of the meat pieces and the effect of different operational variables. The main objective of this study was to evaluate the feasibility of using an ultrasound system and methodology, adapted to the industry requirements, for the online monitoring of the ham dry-salting process. For that purpose, hams were dry salted for different times (4, 10, 11, 14, 16 and 30 days) at 2 degrees C. The cushion zone of the ham was placed over the transducers during salting and ultrasonic signals were taken automatically (5 min interval by using pulse-echo mode. Several methods of signal analysis were considered in order to assess the time of flight (TOF). TOF estimations by means of the energy threshold and cross-correlation methods (between the initial ultrasonic signal and the remaining signals measured during salting and between consecutive signals 5 min apart without interpolation) were affected by the low signal-to-noise ratio and the pulse distortion and were discarded for the online monitoring of ham salting. Otherwise, the cross-correlation method between consecutive signals (5 min apart) with interpolation n = 3 (CCM-CS n = 3), between non-consecutive signals (1 h apart) (CCM-NCS) and the phase spectrum method (PSM), provided close estimations of the variation of the TOF, which correlated well with the ham salt gain (R-2 = 0.83 for CCM-CS n = 3, 0.93 for CCM-NCS and 0.90 for PSM). Consequently, the use of ultrasonic pulse-echo TOF measurements could be considered as a simple, non-invasive, non-destructive and reliable technique for the industrial monitoring of the ham dry-salting process.This work was supported by the Spanish Ministerio de Economia y Competitividad (MINECO), Institute Nacional de Investigacion y Tecnologia Agraria y Alimentaria and European Regional Development Fund (ERDF 2014-2020) (project RTA 2013-00030-C03-02), and by the Universitat Politecnica de Valencia through the FPI grant awarded to Marta de Prados (SP-1.2011-S1-2757).Garcia-Perez, J.; De Prados, M.; Martínez, G.; Gomez Alvarez-Arenas, TE.; Benedito Fort, JJ. (2019). Ultrasonic online monitoring of the ham salting process. Methods for signal analysis: Time of flight calculation. Journal of Food Engineering. 263:87-95. https://doi.org/10.1016/j.jfoodeng.2019.05.032S879526

Soft porous silicone rubbers with ultra-low sound speeds in acoustic metamaterials

Soft porous silicone rubbers are demonstrated to exhibit extremely low sound speeds of tens of m/s for these dense materials, even for low porosities of the order of a few percent. Our ultrasonic experiments show a sudden drop of the longitudinal sound speed with the porosity, while the transverse sound speed remains constant. For such porous elastomeric materials, we propose simple analytical expressions for these two sound speeds, derived in the framework of Kuster and Toksöz, revealing an excellent agreement between the theoretical predictions and the experimental results for both longitudinal and shear waves. Acoustic attenuation measurements also complete the characterization of these soft porous materials.Advanced Materials by DesignInitiative d'excellence de l'Université de Bordeau

Undetectable HCV-RNA at treatment-week 8 results in high-sustained virological response in HCV G1 treatment-experienced patients with advanced liver disease: The International Italian/Spanish Boceprevir/Peginterferon/Ribavirin Name Patients Program

In many countries, first-generation protease inhibitors (PIs)/peginterferon/ribavirin (P/R) still represent the only treatment option for HCV-infected patients. Subjects with advanced disease and previous failure to P/R urgently need therapy, but they are under-represented in clinical trials. All treatment-experienced F3/4 Metavir patients who received boceprevir (BOC)+P/R in the Italian-Spanish Name Patient Program have been included in this study. Multivariate logistic regression analysis (MLR) was used to identify baseline and on-treatment predictors of SVR and adverse events (AEs). Four hundred and sixteen patients, mean age 57.7 (range 25-78 years), 70% males, 69.5% (289/416) F4, 14% (41/289) Child-Pugh class A6, 24% (70/289) with varices and 42% (173/416) prior null responders to P/R, were analysed. Overall, SVR rate (all 381 patients who received one dose of BOC) was 49%, (58% in F3, 45% in F4, 61% in relapsers, 51% in partial, 38% in null responders, and 72% in subjects with undetectable HCV-RNA at treatment-week (TW)8. Among patients with TW8 HCV-RNA 65 1000 IU/L, SVR was 8% (negative predictive value = 92%). Death occurred in 3 (0.8%) patients, while decompensation and infections were observed in 2.9% and 11%, respectively. At MLR, SVR predictors were TW4 HCV-RNA 65 1log10-decline from baseline, undetectable TW8 HCV-RNA, prior relapse, albumin levels 653.5 g/dL and platelet counts 65100 000/lL. Metavir F4, Child-Pugh A6, albumin, platelets, age and female gender were associated with serious and haematological AEs. Among treatment-experienced patients with advanced liver disease eligible for IFN-based therapy, TW8 HCV-RNA characterised the subset with either high or poor likelihood of achieving SVR. Using TW8 HCV-RNA as a futility rule, BOC/P/R appears to have a favourable benefit-risk profile