Label-free highly multimodal nonlinear endoscope.

We demonstrate a 2 mm diameter highly multimodal nonlinear micro-endoscope allowing label-free imaging of biological tissues. The endoscope performs multiphoton fluorescence (3-photon, 2-photon), harmonic generation (second-SHG and third-THG) and coherent anti-Stokes Raman scattering (CARS) imaging over a field of view of 200 µm. The micro-endoscope is based on a double-clad antiresonant hollow core fiber featuring a high transmission window (850 nm to 1800 nm) that is functionalized with a short piece of graded-index (GRIN) fiber. When combined with a GRIN micro-objective, the micro-endoscope achieves a 1.1 µm point spread function (PSF). We demonstrate 3-photon, 2-photon, THG, SHG, and CARS high resolution images of unlabelled biological tissues.

Origin of spontaneous wave mixing processes in multimode GRIN fibers.

We show that geometric parametric instability (GPI) in graded-index multimode fibers is strongly influenced by higher-order dispersion. By measuring the output spectrum for different core radii, we distinguish peaks generated by GPI from other coexisting parametric processes using phase-matching arguments and numerical simulations. We highlight for the first time a non-degenerate GPI process involving two pumps at different wavelengths.

Collision between a dark soliton and a linear wave in an optical fiber.

We report an experimental observation of the collision between a linear wave propagating in the anomalous dispersion region of an optical fiber and a dark soliton located in the normal dispersion region. This interaction results in the emission of a new frequency component whose wavelength can be predicted using phase-matching arguments. The measured efficiency of this process shows a strong dependency with the soliton grayness and the linear wave wavelength, and is in a good agreement with theory and numerical simulations.

Grayness-dependent emission of dispersive waves from dark solitons in optical fibers.

We report the experimental observation of dispersive wave emission from gray solitons propagating in the normal dispersion region of an optical fiber. Besides observing for the first time, to the best of our knowledge, the emission of a dispersive wave from an isolated dark soliton, we show that the dispersive wave frequency and amplitude strongly depend on soliton grayness. This process can be explained by the higher-order dispersion contribution into the phase-matching condition and the grayness of the soliton. Numerical simulations and theoretical predictions are in good agreement with the experiments.

The safety of iloprost in systemic sclerosis in a real-life experience.

Iloprost (ILO) is employed intravenously for the treatment of severe Raynaud phenomenon (RP) and digital ulcers (DU) in systemic sclerosis (SSc). The aim of this study was to evaluate the safety and tolerability of the intravenous treatment with ILO in different phases of SSc. Eighty-one consecutive non-selected SSc patients, all on nifedipine, with moderate RP, treated with ILO infusion, were retrospectively evaluated. Patients were sub classified according to the edematous or fibrotic/atrophic cutaneous phase of the disease. ILO was infused with a progressive increase of the dosage up to the achievement of patient's tolerance, 1 day/week. In cases of slower infusion regimen due to adverse events (AE) at the beginning of the administration, patients received a lower dose of the drug (not possible to quantify precisely the final cumulative dosage). 16/81 SSc patients presented digital edema, 5 developed diarrhea, and 9 developed transient hypotension during the infusion at 20 ml/h that ameliorated when the drug was withdrawn. Moreover, 10/16 edematous patients experienced significant and painful digital swelling, unlike patients in the fibrotic group (p < 0.0001); 11/16 patients reported flushing and 7/16 headache, always controlled with dose tapering below 10 ml/h. In the atrophic/fibrotic phase patients (65/81), 10 developed diarrhea and 24 hypotension at infusion rate of 20 ml/h that led to temporary withdrawal of the drug. When ILO was restarted and kept below 10 ml/h, no side effects were experienced. 23/65 patients experienced flushing and 8/65 headache, all controlled with infusion reduction below 10 ml/h. In these patients, adverse events were significantly less frequent than in the edematous group (p = 0.023 and p = 0.008, respectively). Our data suggest that calcium channel blockers should be transitorily stopped while using ILO and that a pre-treatment approach might reduce or control adverse events. In patients with digital edema, ILO infusion should be carefully employed after the evaluation of patient's drug tolerance.

Modulation instability in the weak normal dispersion region of passive fiber ring cavities.

We report the experimental observation of modulation instability in the weak normal dispersion region of a passive fiber ring cavity. We show that the fourth-order dispersion strongly modifies the dynamics of the cavity through the generation of new instability bands. Experimental results are in excellent agreement with theoretical predictions and numerical simulations.

Spectral broadening of picosecond pulses forming dispersive shock waves in optical fibers.

We investigate analytically, numerically, and experimentally the spectral broadening of pulses that undergo the formation of dispersive shocks, addressing in particular pulses in the range of tens of ps generated via electro-optic modulation of a continuous-wave laser. We give an analytical estimate of the maximal spectral extension and show that super-Gaussian waveforms favor the generation of flat-topped spectra. We also show that the weak residual background of the modulator produces undesired spectral ripples. Spectral measurements confirm our estimates and agree well with numerical integration of the nonlinear Schrödinger equation.

Longitudinal soliton tunneling in optical fiber.

We report the observation of the longitudinal soliton tunneling effect in axially varying optical fibers. A fundamental soliton, initially propagating in the anomalous dispersion region of a fiber, can pass through a normal dispersion barrier without being substantially affected. We perform experimental studies by means of spectral and temporal characterizations that show the evidence of the longitudinal soliton tunneling process. Our results are well supported by numerical simulations using the generalized nonlinear Schrödinger equation.

Dynamics of Turing and Faraday instabilities in a longitudinally modulated fiber-ring cavity.

We experimentally investigate the round-trip-to-round-trip dynamics of the modulation instability spectrum in a passive fiber-ring cavity presenting an inhomogeneous dispersion profile. By implementing a real-time spectroscopy technique, we are able to record successive single-shot spectra, which display the evolution of the system toward a stationary state. We find that the two instability regimes (Turing and Faraday) that compete in this kind of inhomogeneous cavity not only differ by their characteristic frequency but also by their dynamical behavior. The dynamic transition between those two regimes of instability is also presented.

Heteroclinic Structure of Parametric Resonance in the Nonlinear Schrödinger Equation.

We show that the nonlinear stage of modulational instability induced by parametric driving in the defocusing nonlinear Schrödinger equation can be accurately described by combining mode truncation and averaging methods, valid in the strong driving regime. The resulting integrable oscillator reveals a complex hidden heteroclinic structure of the instability. A remarkable consequence, validated by the numerical integration of the original model, is the existence of breather solutions separating different Fermi-Pasta-Ulam recurrent regimes. Our theory also shows that optimal parametric amplification unexpectedly occurs outside the bandwidth of the resonance (or Arnold tongues) arising from the linearized Floquet analysis.

Emission of dispersive waves from a train of dark solitons in optical fibers.

We report the experimental observation of multiple dispersive waves (DWs) emitted in the anomalous dispersion region of an optical fiber from a train of dark solitons. Each DW can be associated to one dark soliton of the train, using phase-matching arguments involving higher-order dispersion and soliton velocity. For a large number of dark solitons (>10), we observe the formation of a continuum associated with the efficient emission of DWs.

Shock wave generation triggered by a weak background in optical fibers.

We experimentally report the observation of dispersive shock waves from a short pulse superimposed onto a small continuous wave background in optical fibers. We show that the background allows us to strongly enhance the extension and contrast of the oscillatory wave train inherent to the dispersive shock. More than seven periods of oscillations with high contrast are observed experimentally and confirmed with numerical simulations. The dynamics of the process are simply explained from spectro-temporal representations.

Solitonization of a dispersive wave.

We report the observation of a nonlinear propagation scenario in which a dispersive wave is transformed into a fundamental soliton in an axially varying optical fiber. The dispersive wave is initially emitted in the normal dispersion region and the fiber properties change longitudinally so that the dispersion becomes anomalous at the dispersive wave wavelength, which allows it to be transformed into a soliton. The solitonic nature of the field is demonstrated by solving the direct Zakharov-Shabat scattering problem. Experimental characterization performed in spectral and temporal domains show evidence of the solitonization process in an axially varying photonic crystal fiber.

HCV - Estimation of the number of diagnosed patients eligible to the new anti-HCV therapies in Italy.

OBJECTIVE: The present research wants to take a picture of the current epidemiological scenario regarding HCV infection in Italy. Studies used to estimate HCV burden of illness in Italy were so far local and performed a number of years ago, not mirroring the state of the art. EpaC wanted to provide a real number of diagnosed patients, eligible to new anti-HCV therapies. PATIENTS AND METHODS: EpaC is the most important Italian NGO for hepatopathic patients. A number of sources were cross-checked. Starting from all regional data regarding HCV-related exemptions, a correction/integration was performed with online questionnaire to associated patients (from which we derived patients cured and also other/no exemptions); survey to all prescribing centers in Italy (from which we derived the percentage of ineligible patients); prevalence of particular subpopulations was also collected (prisoners and HIV/HCV coinfected); calculations of new diagnosed, dead and cured patients in 2015. Excluded patients were illegal immigrants and active drug addicts (subpopulations currently rarely cured). RESULTS: A total of 221,549 patients were derived from regional exemptions databases and the mean national prevalence was 0.364%. Adding patients without exemptions/other exemptions, total was 308,624. We deducted the yearly deaths, cured and not eligible patients and, last, integrated with coinfected and prisoner special groups. Prevalence was also estimated at regional level, highlighting a reduction of the typical North-to-South prevalence gradient. Applying the above-mentioned corrections/integrations, total diagnosed and eligible HCV patients in Italy who can be immediately cured are supposed to range 163,148-187,756. CONCLUSIONS: This is a research aimed at filling an informative gap able to provide useful actual information in terms of HCV patients real-life management and future resource allocation. These data may be considered the basis for policy- and decision-makers to plan and manage patients ready to be cured. The research does not provide information on patients not yet diagnosed.

Optimal frequency conversion in the nonlinear stage of modulation instability.

We investigate multi-wave mixing associated with the strongly pump depleted regime of induced modulation instability (MI) in optical fibers. For a complete transfer of pump power into the sideband modes, we theoretically and experimentally demonstrate that it is necessary to use a much lower seeding modulation frequency than the peak MI gain value. Our experiment shows that, at such optimal modulation frequency, a record 95 % of the output pump power is frequency converted into the comb of sidebands, in good quantitative agreement with analytical predictions based on the simplest exact breather solution of the nonlinear Schrodinger ¨ equation.

Bouncing of a dispersive wave in a solitonic cage.

We report the experimental observation of a weak dispersive wave trapped within a cage formed by two solitons in an optical fiber. We show that the dispersive wave bouncing is accompanied by a back-and-forth wavelength conversion of the probe to an idler wave. Additionally, we observed the destruction of the soliton cage when the dispersive wave power is increased, leading to the collision of the solitons.

Observation of the stepwise blue shift of a dispersive wave preceding its trapping by a soliton.

The trapping of a weak dispersive wave by an intense soliton is a complex process occurring at the early stage of supercontinuum generation. It is theoretically predicted to arise from multiple soliton-dispersive wave interactions, producing a stepwise frequency blue shift of the dispersive wave. We report here the first experimental evidence of this frequency blue shift using a tapered fiber which acts as a prism, allowing to disperse the blue spectral components in order to identify unambiguously each soliton-dispersive wave collision.

Soliton annihilation into a polychromatic dispersive wave.

We investigate the propagation of a soliton in an axially varying optical fiber with a progressive change from anomalous to normal dispersion regimes. Spectral and temporal measurements provide evidence for a complete annihilation of the soliton, which explodes into a polychromatic dispersive wave. This interpretation is confirmed by numerical solution of the generalized nonlinear Schrödinger equation.

Emission of multiple dispersive waves from a single Raman-shifting soliton in an axially-varying optical fiber.

We provide the experimental demonstration of the generation of multiple dispersive waves from a single soliton propagating in the vicinity of the first zero-dispersion wavelength of an axially-varying optical fiber. The fiber is designed such that the Raman-shifting soliton successively hits three times the longitudinally evolving zero-dispersion wavelength, which results in the emission of three distinct dispersive waves at different fiber lengths. These results illustrate how suitably controlled axially-varying fibers allow to tailor the soliton dynamics in a very accurate way.

Zero focusing via competing nonlinearities in beta-barium-borate crystals.

We investigate nonlinear focusing behavior of light beams propagating in beta-barium-borate crystals under mismatched second-harmonic generation. We clearly identify experimentally multiple self-focusing and defocusing regions against the orientation angle and the condition where competing quadratic and cubic nonlinearities perfectly compensate each other (zero-focusing point).