Randomized, placebo-controlled study on efficacy, safety and tolerability of drug-induced defibrinogenation for sudden sensorineural hearing loss: the lessons learned.

PURPOSE: Disturbance of cochlear microcirculation is discussed as final common pathway of various inner ear diseases. Hyperfibrinogenemia causing increased plasma viscosity is a possible factor for a critical reduction of cochlear blood flow that might lead to sudden sensorineural hearing loss (SSHL). The aim was to determine the efficacy and safety of drug-induced defibrinogenation by ancrod for SSHL. METHODS: Double-blind, randomized, placebo-controlled, multicenter, parallel group, phase II (proof-of-concept) study (planned enrollment: 99 patients). Patients received an infusion of ancrod or placebo (day 1) followed by subcutaneous administrations (day 2, 4, 6). Primary outcome was the change in pure tone audiogram air conduction average until day 8. RESULTS: The study was terminated early due to slow recruiting (31 enrolled patients: 22 ancrod, 9 placebo). A significant improvement of hearing loss was registered in both groups (ancrod: - 14.3 dB ± 20.4 dB, - 39.9% ± 50.4%; placebo: - 22.3 dB ± 13.7 dB, - 59.1% ± 38.0%). A statistically significant group-difference was not detected (p = 0.374). Placebo response of 33.3% complete and 85.7% at least partial recovery was observed. Plasma fibrinogen levels were reduced significantly by ancrod (baseline: 325.2 mg/dL, day 2: 107.2 mg/dL). Ancrod was tolerated well, no adverse drug reaction was of severe intensity, no serious adverse events occurred. CONCLUSION: Ancrod reduced fibrinogen levels that support its mechanism of action. The safety profile can be rated positively. Since the planned number of patients could not be enrolled, no efficacy conclusion can be drawn. The high rate of placebo response challenges clinical trials for SSHL and needs to be considered in future investigations. Trial registrations This study was registered in the EU Clinical Trials Register, EudraCT-No. 2012-000066-37 at 2012-07-02.

Comparison of three focus sensors for optical topography measurement of rough surfaces.

The study compares three variants of focus sensors designed for the optical topography measurement of rough surface specimens with submicron accuracy. We present a theoretical analysis of the focus sensor principles and the experimental measurements with a single point laser probe. A low coherent illumination beam was provided by a monochromatic laser source and a rotating diffuser, which reduced the speckles generated by the rough surface. The reflected beam was modulated by three specific optical elements (axicon, double wedge prism, four spherical lenses) realized by a spatial light modulator. A digital camera detected the output intensity patterns that were evaluated by the intensity centroid method. The results showed a good coincidence of the surface profiles obtained by the three sensor variants with the root-mean-square deviations below one micron. We discuss the results obtained for several specimens with various surface roughness and compare the differences between the three focus sensor variants.

Detection techniques in low-coherence interferometry and their impact on overall measurement accuracy.

This paper deals with interference fringe center detection techniques used in low-coherence interferometry for contactless 3D inspection of macroscopic objects. It presents a complex analysis of several frequently used detection techniques and shows their impact on the measurement accuracy. The analysis compares those techniques in terms of computational complexity, measurement accuracy, and resistance to optical dispersion caused by wedge-shaped optical components.

Strong near-field enhancement of radiative heat transfer between metallic surfaces.

Near-field heat transfer across a gap between plane-parallel tungsten layers in vacuo was studied experimentally with the temperature of the cold sample near 5 K and the temperature of the hot sample in the range 10-40 K as a function of the gap size d. At gaps smaller than one-third of the peak wavelength λ(m) given by Wien's displacement law, the near-field effect was observed. In comparison with blackbody radiation, hundred times higher values of heat flux were achieved at d≈1 µm. Heat flux normalized to the radiative power transferred between black surfaces showed scaling (λ(m)/d)(n), where n≈2.6. This Letter describes the results of experiment and a comparison with present theory over 4 orders of magnitude of heat flux.

Quantification of STEM Images in High Resolution SEM for Segmented and Pixelated Detectors.

The segmented semiconductor detectors for transmitted electrons in ultrahigh resolution scanning electron microscopes allow observing samples in various imaging modes. Typically, two standard modes of objective lens, with and without a magnetic field, differ by their resolution. If the beam deceleration mode is selected, then an electrostatic field around the sample is added. The trajectories of transmitted electrons are influenced by the fields below the sample. The goal of this paper is a quantification of measured images and theoretical study of the capability of the detector to collect signal electrons by its individual segments. Comparison of measured and ray-traced simulated data were difficult in the past. This motivated us to present a new method that enables better comparison of the two datasets at the cost of additional measurements, so-called calibration curves. Furthermore, we also analyze the measurements acquired using 2D pixel array detector (PAD) that provide a more detailed angular profile. We demonstrate that the radial profiles of STEM and/or 2D-PAD data are sensitive to material composition. Moreover, scattering processes are affected by thickness of the sample as well. Hence, comparing the two experimental and simulation data can help to estimate composition or the thickness of the sample.

Nanostructures for Achieving Selective Properties of a Thermophotovoltaic Emitter.

This paper focuses on the research and development of a suitable method for creating a selective emitter for the visible and near-infrared region to be able to work optimally together with silicon photovoltaic cells in a thermophotovoltaic system. The aim was to develop a new method to create very fine structures beyond the conventional standard (nanostructures), which will increase the emissivity of the base material for it to match the needs of a selective emitter for the VIS and NIR region. Available methods were used to create the nanostructures, from which we eliminated all unsuitable methods; for the selected method, we established the optimal procedure and parameters for their creation. The development of the emitter nanostructures included the necessary substrate pretreatments, where great emphasis was placed on material purity and surface roughness. Tungsten was purposely chosen as the main material for the formation of the nanostructures; we verified the effect of the formed structure on the resulting emissivity. This work presents a new method for the formation of nanostructures, which are not commonly formed in such fineness; by this, it opens the way to new possibilities for achieving the desired selectivity of the thermophotovoltaic emitter.

Nanoscale Estimation of Coating Thickness on Substrates via Standardless BSE Detector Calibration.

The thickness of electron transparent samples can be measured in an electron microscope using several imaging techniques like electron energy loss spectroscopy (EELS) or quantitative scanning transmission electron microscopy (STEM). We extrapolate this method for using a back-scattered electron (BSE) detector in the scanning electron microscope (SEM). This brings the opportunity to measure the thickness not just of the electron transparent samples on TEM mesh grids, but, in addition, also the thickness of thin films on substrates. Nevertheless, the geometry of the microscope and the BSE detector poses a problem with precise calibration of the detector. We present a simple method which can be used for such a type of detector calibration that allows absolute (standardless) measurement of thickness, together with a proof of the method on test samples.

Comparison of Lifetime of the PVD Coatings in Laboratory Dynamic Impact Test and Industrial Fine Blanking Process.

Protective hard PVD coatings are used to improve the endurance of the tools exposed to repeated impact load, e.g., fine blanking punches. During the fine blanking process, a coated punch repeatedly impacts sheet metal. Thus, the coating which protects the punch surface is exposed to the dynamic impact load. On the other hand, the laboratory method of dynamic impact testing is well known and used for the development and optimization of protective coatings. This paper is focused on the comparison of tool life and lifetime of the industrial prepared PVD coatings exposed to repeated dynamic impact load in the industrial fine blanking process and the laboratory dynamic impact testing. Three different types of protective coatings were tested and the results were discussed. It was shown that the lifetime of coated specimens in both the fine blanking and the dynamic impact processes was influenced by similar mechanical properties of the protective coatings. The qualitative comparison shows that the lifetime obtained by the dynamic impact test was the same as the lifetime obtained by the industrial fine blanking process. The laboratory impact test appears to be a suitable alternative for the optimisation and development of protective PVD coatings for punches used in the industrial fine blanking process.