The optimal timing of hepatitis C therapy in liver transplant-eligible patients: Cost-effectiveness analysis of new opportunities.

Different strategies of DAAs treatment are currently possible both pre- and postliver transplantation (LT). Clinical and economic consequences of these strategies still need to be adequately investigated; this study aims at assessing their cost-effectiveness. A decision analytical model was created to simulate the progression of HCV-infected patients listed for decompensated cirrhosis (DCC) or for hepatocellular carcinoma (HCC). Three DAAs treatment strategies were compared: (i) a 12-week course of DAAs prior to transplantation (PRE-LT), (ii) a 4-week course of DAAs starting at the time of transplantation (PERI-LT) and (iii) a 12-week course of DAAs administered at disease recurrence (POST-LT). The population was substratified according to HCC presence and, in those without HCC, according to the MELD score at listing. Data on DAAs effectiveness were estimated using a cohort of patients still followed by 11 transplant centres of the European Liver and Intestine Transplant Association and by data available in the literature. In this study, PRE-LT treatment strategy was dominant for DCC patients with MELD<16 and cost-effective for those with MELD16-20, while POST-LT strategy emerged as cost-effective for DCC patients with MELD>20 and for those with HCC. Sensitivity analyses confirmed PRE-LT as the cost-effective strategy for patients with MELD≤20. In conclusion, PRE-LT treatment is cost-effective for patients with MELD≤20 without HCC, while treatments after LT are cost-effective in cirrhotic patients with MELD>20 and in those with HCC. It is worth reminding, though, that the final choice of a specific regimen at the patient level will have to be personalized based on clinical, social and transplant-related factors.

Catalytic Effect of Pd Clusters in the Poly(N-vinyl-2-pyrrolidone) Combustion.

Pd(0) is able to catalyze oxygen-involving reactions because of its capability to convert molecular oxygen to the very reactive atomic form. Consequently, the embedding of a little amount of Pd(0) clusters in polymeric phases can be technologically exploited to enhance the incineration kinetic of these polymers. The effect of nanostructuration on the Pd(0) catalytic activity in the polymer incineration reaction has been studied using poly(N-vinyl-2-pyrrolidone) ([Formula: see text] = 10,000 gmol-1) as polymeric model system. A change in the PVP incineration kinetic mechanism with significant increase in the reaction rate was experimentally found. The kinetic of the Pd(0)-catalyzed combustion has been studied by isothermal thermogravimetric analysis. After a short induction time, the combustion in presence of Pd(0) clusters shifted to a zero-order kinetic from a second-order kinetic control, which is operative in pure PVP combustion reaction. In addition, the activation energy resulted much lowered compared to the pure PVP incineration case (from 300 to 260 kJ/mol).

Mechanical properties of low-density polyethylene filled by graphite nanoplatelets.

The mechanical properties of GNP/LDPE nanocomposites (graphite nanoplatelets/low density polyethylene) have been investigated, in order to establish the effect of nanoscale reinforcement within the polymer matrix. Results show that the presence of the filler does not involve a change in the microscopic structure of the polymer. However, on a macroscopic scale, GNPs limit the mobility of the polymer chains, resulting in an increase in stiffness for the final composite. Orientation of GNPs within the LDPE matrix is also an important issue that affects mechanical properties and it has been evaluated by testing nanocomposites made by different manufacturing techniques (compression moulding and blown extrusion). The comparison between the experimental data and the Halpin-Tsai model shows that the orientation of GNPs due to the extrusion process leads to values of tensile modulus higher than that obtained with the randomly oriented disposition resulting from the compression moulding technique.

Implications of PNPLA3 polymorphism in chronic hepatitis C patients receiving peginterferon plus ribavirin.

BACKGROUND: Homozygosity for the PNPLA3 p.I148M polymorphism influences steatosis and fibrogenesis in chronic hepatitis C (CHC). AIM: To evaluate the effect of p.148M/M on sustained virological response (SVR) and viral kinetics in patients who underwent antiviral therapy with peg-interferon and ribavirin, stratified according to viral genotype and fibrosis severity, and secondarily, the interaction with interleukin-28B ( IL28B ) genotype on liver damage. METHODS: In this observational study, we considered 602 treatment-naïve consecutive patients from tertiary referral centres in Milan and Vienna [61% genotype 1 (G1), 30% advanced fibrosis, 33% IL28B rs12979860 CC]. RESULTS: The p.148M/M genotype, detected in 8% of patients, did not influence SVR in the overall series (P = 0.29), but it was associated with SVR (3/17, 17% vs. 56/121, 46%; P = 0.034) and complete early viral response (4/17, 23% vs. 68/121, 56%; P = 0.018) in G1/4 patients with advanced fibrosis. After adjustment for age, viral load, IL28B CC genotype, treatment dose, and steatosis, p.148M/M remained a predictor of SVR in G1/4 patients with advanced fibrosis (OR 0.23, 95% CI 0.04-0.87). The p.148M/M genotype was associated with more advanced fibrosis in the overall series (P = 0.049), whereas the rs12979860 IL28B CC genotype only in patients negative for p.148M/M (P = 0.017), independently of age, BMI and alanine transaminase levels (OR 1.51, 95% CI 1.01-2.27). CONCLUSIONS: PNPLA3 p.148M/M genotype was negatively associated with SVR and early viral kinetics independently of steatosis, albeit only in difficult-to-cure G1/4 patients with advanced fibrosis, whereas stratification for the p.148M/M PNPLA3 genotype unmasked an association between IL28B CC genotype and more severe liver fibrosis.

Tunable liquid microlens arrays in electrode-less configuration and their accurate characterization by interference microscopy.

A special class of tunable liquid microlenses is presented here. The microlenses are generated by an electrowetting effect under an electrode-less configuration and they exhibit two different regimes that are named here as separated lens regime (SLR) and wave-like lens regime (WLR). The lens effect is induced by the pyroelectricity of polar dielectric crystals, as was proved in principle in a previous work by the same authors (S. Grilli et al., Opt. Express 16, 8084, 2008). Compared to that work, the improvements to the experimental set-up and procedure allow to reveal the two lens regimes which exhibit different optical properties. A digital holography technique is used to reconstruct the transmitted wavefront during focusing and a focal length variation in the millimetre range is observed. The tunability of such microlenses could be of great interest to the field of micro-optics thanks to the possibility to achieve focus tuning without moving parts and thus favouring the miniaturization of the optical systems.

Super-resolution in digital holography by a two-dimensional dynamic phase grating.

An approach that uses an electro-optically tunable two dimensional phase grating to enhance the resolution in digital holographic microscopy is proposed. We show that, by means of a flexible hexagonal phase grating, it is possible to increase the numerical aperture of the imaging system, thus improving the spatial resolution of the images in two dimensions. The augment of the numerical aperture of the optical system is obtained by recording spatially multiplexed digital holograms. The grating tuneability allows one to adjust the intensity among the spatially multiplexed holograms maximizing the grating diffraction efficiency. Furthermore we demonstrate that the flexibility of the numerical reconstruction allows one to use selectively the diffraction orders carrying useful information for increasing the spatial resolution. The proposed approach can improve the capabilities of digital holography in three-dimensional imaging and microscopy.

Non-collinear quasi phase matching and annular profiles in difference frequency generation with focused Gaussian beams.

We present and experimentally test a simple model for difference frequency generation (DFG) in periodically-poled crystals with gaussian pumping beams. Focusing of input beams originates several non-collinear quasi-phase-matching configurations of the interacting wavevectors, which contribute to the idler output field. In this picture, we accurately describe a number of effects, such as the occurrence of annular idler intensity profiles and the asymmetric trend of DFG power vs temperature. Finally, we quantitatively test the model by means of an indirect measurement of the crystal poling period.

Liquid micro-lens array activated by selective electrowetting on lithium niobate substrates.

Lens effect was obtained in an open microfluidic system by using a thin layer of liquid on a polar electric crystal like LiNbO3. An array of liquid micro-lenses was generated by electrowetting effect in pyroelectric periodically poled crystals. Compared to conventional electrowetting devices, the pyroelectric effect allowed to have an electrode-less and circuit-less configuration. An interferometric technique was used to characterize the curvature of the micro-lenses and the corresponding results are presented and discussed. The preliminary results concerning the imaging capability of the micro-lens array are also reported.

Phase map retrieval in digital holography: avoiding the undersampling effect by a lateral shear approach.

In digital holography (DH) the numerical reconstruction of the whole wavefront allows one to extract the wrapped phase map mod, 2 pi. It can occur that the reconstructed wrapped phase map in the image plane is undersampled because of the limited pixel size in that plane. In such a case the phase distribution cannot be retrieved correctly by the usual unwrapping procedures. We show that the use of the digital lateral-shearing interferometry approach in DH provides the correct reconstruction of the phase map in the image plane, even in extreme cases where the phase profile changes very rapidly. We demonstrate the effectiveness of the method in a particular case where the profile of a highly curved silicon microelectromechanical system membrane has to be reconstructed.

Interrogation of fiber Bragg-grating resonators by polarization-spectroscopy laser-frequency locking.

We report on an optically-based technique that provides an efficient way to track static and dynamic strain by locking the frequency of a diode laser to a fiber Bragg-grating Fabry-Pérot cavity. For this purpose, a suitable optical frequency discriminator is generated exploiting the fiber natural birefringence and that resulting from the gratings inscription process. In our scheme, a polarization analyzer detects dispersive-shaped signals centered on the cavity resonances without need for additional optical elements in the resonator or any laser-modulation technique. This method prevents degradation of the resonator quality and maintains the configuration relatively simple, demonstrating static and dynamic mechanical sensing below the picostrain level.

Amplitude and phase reconstruction of photorefractive spatial bright-soliton in LiNbO3 during its dynamic formation by digital holography.

The time behaviour of bright spatial solitons in congruent undoped lithium niobate crystal is experimentally investigated. Full field characterization of the optical wavefront emerging from the crystal during the soliton formation process is performed by digital holographic method. Experimental results of the amplitude and phase maps of the field distribution at the exit face of the crystal allow the real-time monitoring of the evolution of the soliton beam from the application of the external field to the end of the process when the generation of the channel waveguide appears to be stable. The features of the dynamics of the soliton formation are visualized, analyzed and compared to a time-dependent numerical model.

Quantitative Phase Microscopy of microstructures with extended measurement range and correction of chromatic aberrations by multiwavelength digital holography.

Quantitative Phase Microscopy (QPM) by interferometric techniques can require a multiwavelength configuration to remove 2pi ambiguity and improve accuracy. However, severe chromatic aberration can affect the resulting phase-contrast map. By means of classical interference microscope configuration it is quite unpractical to correct such aberration. We propose and demonstrate that by Digital Holography (DH) in a microscope configuration it is possible to clear out the QPM map from the chromatic aberration in a simpler and more effective way with respect to other approaches. The proposed method takes benefit of the unique feature of DH to record in a plane out-of-focus and subsequently reconstruct numerically at the right focal image plane. In fact, the main effect of the chromatic aberration is to shift differently the correct focal image plane at each wavelength and this can be readily compensated by adjusting the corresponding reconstruction distance for each wavelength. A procedure is described in order to determine easily the relative focal shift among different imaging wavelengths by performing a scanning of the numerical reconstruction along the optical axis, to find out the focus and to remove at the same time the chromatic aberration.

Phase-shifting point-diffraction interferometer developed by using the electro-optic effect in ferroelectric crystals.

A novel and simple phase-shifting point-diffraction interferometer using a z-cut lithium niobate wafer is proposed. The pinhole is realized by an optical lithography process, aluminum deposition, and subsequent lift-off on the surface of the wafer. The phase shifting is obtained by inducing the electro-optic effect along the z crystal axis. We demonstrate experimentally the possibility of retrieving an aberrated wavefront.

Tunable two-dimensional hexagonal phase array in domain-engineered Z-cut lithium niobate crystal.

An optical phase array with tunable phase step is demonstrated. The phase array consists of a two-dimensional hexagonal lattice of inverted ferroelectric domains fabricated on a Z-cut lithium niobate substrate. The electro-optically tunable phase step is obtained by the application of an external electric field along the z axis of the crystal via transparent electrodes. Theoretical analysis and experimental results are presented, showing that a tunable and flexible adaptive optical illuminator device can be realized by combining the electro-optic tunability with the Talbot effect. Generation of a multiplicity of light patterns is shown.

Quantitative phase-contrast microscopy by a lateral shear approach to digital holographic image reconstruction.

Combining the concept of lateral shear interferometry (LSI) within a digital holography microscope, we demonstrate that it is possible to obtain quantitative optical phase measurement in microscopy by a new single-image-processing procedure. Numerical lateral shear of the reconstructed wavefront in the image plane makes it possible to retrieve the derivative of the wavefront and remove the defocus aberration term introduced by the microscope objective. The method is tested to investigate a silicon structure and a mouse cell line.

Recovering correct phase information in multiwavelength digital holographic microscopy by compensation for chromatic aberrations.

We demonstrate experimentally that correct phase imaging without 2pi ambiguity is obtainable in digital holography by using a multiwavelength approach in the microscope configuration. We describe a general approach for removing chromatic aberrations and for controlling the pixel size of the reconstructed phase image in multiwavelength digital holography when the Fourier transform method is adopted for the numerical reconstruction of digital holograms. The retrieved phase is affected by the unavoidable, unwanted chromatic aberration. The correct phase can be obtained by evaluating the phase from the reference holograms reconstructed at different wavelengths to compensate for the chromatic aberration.

Two-dimensional mapping of electro-optic phase retardation in lithium niobate crystals by digital holography.

We demonstrate accurate two-dimensional mapping of the phase retardation induced by the electro-optic effect in lithium niobate crystals. Off-axis digital holography is used to investigate congruent z-cut crystals. The spatially resolved optical path difference is interferometrically measured while a linearly rising voltage ramp is applied to the crystal. This procedure provides information on the uniformity of crystals' electro-optic properties and offers the ability to detect the presence of defects that is of fundamental importance for reliable processing of photonic devices.

Optical properties of waveguides written by a 26 MHz stretched cavity Ti:sapphire femtosecond oscillator.

We report on the fabrication, by a 26 MHz stretched-cavity femtosecond Ti:sapphire oscillator, of optical waveguides in different glass substrates, and their optical characterization. Operation of these waveguides in the telecom range at 1.55 microm is demonstrated. Digital holography microscopy is used to measure their refractive index profile. The results evidence a strong dependence of the fabrication process on the glass matrix.

Time-resolved contrast function and optical characterization of spatially varying absorptive inclusions at different depths in diffusing media.

The role of a spatially varying absorptive inhomogeneity located at different depths within a turbid material has been investigated. This inhomogeneity has been characterized by a spatially dependent Gaussian distribution of its absorption coefficient. The present study has been performed calculating the time-resolved contrast function in the framework of the first-order perturbative approach to the diffusion equation for a slab geometry and a coaxial measurement scheme. The model has allowed us to take into account different locations of the inclusion along the source-detector axis. The accuracy of time-resolved contrast predictions has been analyzed through comparisons with results of the finite element method that has been used to numerically solve the diffusion equation. Recovery of the absorption perturbation parameter of the inhomogeneity for different axial positions has also been investigated.