Optimization of signal-to-noise ratio in short-duration SEP recordings by variation of stimulation rate

Objective: The intraoperative averaging of the somatosensory evoked potential (SEP) requires reliable recordings within the shortest possible duration. We here systematically optimized the repetition rate of stimulus presentation. Methods: We recorded medianus and tibial nerve SEP during 22 surgeries and varied the rate of stimulus presentation between 2.7 Hz and 28.7 Hz. We randomly sampled a number of sweeps corresponding to recording durations up to 20 s and calculated the signal-to-noise ratio (SNR). Results: For the medianus nerve at 5 s recording duration, SEP stimulation rate at 12.7 Hz obtained the highest median SNR = 22.9 for the N20, which was higher than for rate 4.7 Hz (p = 1.5e-4). When increasing the stimulation rate, latency increased and amplitude decayed for cortical but not for peripheral recording sites. For the tibial nerve, the rate 4.7 Hz achieved the highest SNR for all durations. Conclusions: We determined the time-dependence of SNR for N20 and elucidated the underlying physiology. For short recordings, rapid reduction of noise through averaging at high stimulation rate outweighs the disadvantage of smaller amplitude. Significance: For a short duration of medianus nerve SEP recording only, it may be advantageous to stimulate with a repetition rate of 12.7 Hz. Keywords: Erb’s point; High frequency oscillation; Intraoperative neuromonitoring; Neurosurgery; Peripheral nerve conduction; Stimulation frequency

Engineering a 3D in vitro model of human skeletal muscle at the single fiber scale

The reproduction of reliable in vitro models of human skeletal muscle is made harder by the intrinsic 3D structural complexity of this tissue. Here we coupled engineered hydrogel with 3D structural cues and specific mechanical properties to derive human 3D muscle constructs ("myobundles") at the scale of single fibers, by using primary myoblasts or myoblasts derived from embryonic stem cells. To this aim, cell culture was performed in confined, laminin-coated micrometric channels obtained inside a 3D hydrogel characterized by the optimal stiffness for skeletal muscle myogenesis. Primary myoblasts cultured in our 3D culture system were able to undergo myotube differentiation and maturation, as demonstrated by the proper expression and localization of key components of the sarcomere and sarcolemma. Such approach allowed the generation of human myobundles of ~10 mm in length and ~120 \u3bcm in diameter, showing spontaneous contraction 7 days after cell seeding. Transcriptome analyses showed higher similarity between 3D myobundles and skeletal signature, compared to that found between 2D myotubes and skeletal muscle, mainly resulting from expression in 3D myobundles of categories of genes involved in skeletal muscle maturation, including extracellular matrix organization. Moreover, imaging analyses confirmed that structured 3D culture system was conducive to differentiation/maturation also when using myoblasts derived from embryonic stem cells. In conclusion, our structured 3D model is a promising tool for modelling human skeletal muscle in healthy and diseases conditions

Changes of cellular expression of mRNA for tropoelastin in the intraembryonic arterial vessels of developing chick revealed by in situ hybridization.

The pattern of expression of tropoelastin mRNA in the arterial tree of developing chick has been studied by in situ hybridization. Significant hybridization was noted in 5.5-day embryos in the region of the truncus arteriosus where aorta and pulmonary artery had newly separated. The activation of expression then propagated centrifugally and longitudinal gradients of mRNA decreasing from the heart to the periphery were established. For almost two-thirds of the embryonic period, the hybridization signal was rather uniform over the entire wall of the arterial vessels. Later, however, its distribution varied depending on the type of artery (elastic or muscular) and on the developmental stage. A radial gradient of tropoelastin mRNA expression decreasing in the in-out direction was formed in elastic arteries. This was first seen in the pulmonary artery (15-day chick embryos) and became detectable in the vessels of the general circulation only much later (2 weeks after hatching). The appearance of the radial gradient was followed by a general reduction of mRNA synthesis. In muscular arteries radial gradients were also established, but had, however, an opposite polarity; in small arteries a ring of hybridization was evident at the media-adventitia border. The results indicate that the expression of the tropoelastin gene in cells of the arterial wall is finely regulated, depending on the coordinates in the arterial tree, the type of artery and the organ supplied

Removal of Cu(II) ions from water using thermally-treated horn–hoof powder as biosorbent

In this work, thermally-treated horn-hoof powder was studied as biosorbent to remove copper (II) ions from aqueous solutions. Adsorption of copper onto horn-hoof powder was tested in batch process at different experimental conditions. The effect of the initial metal ion concentration, biosorbent dosage, contact time, pH and temperature were investigated with respect to the biosorption characteristics of Cu(II) ion on the horn-hoof powder. The biosorbent characterization was carried out by Fourier transform infrared spectroscopy, mini-cell electrophoresis, BET and particle sizing analysis. According to the tests, the adsorption equilibrium time was reached within 48h and the optimum adsorption of Cu(II) ions took place at the pH value of 5.5. The Langmuir adsorption isotherm was successfully applied to the biosorption process of Cu(II) ions onto horn-hoof powder. The thermodynamic and kinetic data suggested that the biosorption process is an endothermic process involving chemical reactions and following a pseudo-second-order model

Critical Aspects in the Preparation of Extemporaneous Flecainide Acetate Oral Solution for Paediatrics

The availability of liquid oral preparations compounded by pharmacists is essential to meet paediatric needs which remain unanswered by the pharmaceutical industry. Unfortunately, compendial monographs are often not available and, in many cases, pre-formulation studies (e.g., compatibility with other excipients and solubility evaluations) are not performed in-depth, leading, in some rare cases, to the inadvertent administration of a toxic dose. In this study, the preparation of an oral liquid formulation for paediatric use, containing flecainide acetate at different strengths, was considered, taking into account the possible effects of conventionally used excipients. First, the optimal vehicle was selected based on a solubility study, evidencing some unexpected formations of precipitates. As a matter of fact, the buffers commonly used for oral solutions significantly reduced flecainide solubility, and the concomitant presence of citrate buffer and methylparaben even caused the formation of non-resuspendable crystals. Then, chemical, physical, and microbiological stability were assessed. Solutions at strengths of 10 and 20 mg/mL flecainide acetate were stable up to 8 weeks when compounded by using a 40% sucrose solution as a vehicle. Microbiological data showed that the use of methylparaben was not necessary over this time period

Critical Aspects in the Preparation of Extemporaneous Flecainide Acetate Oral Solution for Paediatrics

The availability of liquid oral preparations compounded by pharmacists is essential to meet paediatric needs which remain unanswered by the pharmaceutical industry. Unfortunately, compendial monographs are often not available and, in many cases, pre-formulation studies (e.g., compatibility with other excipients and solubility evaluations) are not performed in-depth, leading, in some rare cases, to the inadvertent administration of a toxic dose. In this study, the preparation of an oral liquid formulation for paediatric use, containing flecainide acetate at different strengths, was considered, taking into account the possible effects of conventionally used excipients. First, the optimal vehicle was selected based on a solubility study, evidencing some unexpected formations of precipitates. As a matter of fact, the buffers commonly used for oral solutions significantly reduced flecainide solubility, and the concomitant presence of citrate buffer and methylparaben even caused the formation of non-resuspendable crystals. Then, chemical, physical, and microbiological stability were assessed. Solutions at strengths of 10 and 20 mg/mL flecainide acetate were stable up to 8 weeks when compounded by using a 40% sucrose solution as a vehicle. Microbiological data showed that the use of methylparaben was not necessary over this time period

Industrial computational fluid dynamics tools for the evaluation of aerodynamic coefficients

An automatic differentiation techniqueis applied here to anindustrial computational fluid dynamics code with the goal of efficiently evaluating aerodynamic coefficients. Basic concepts about the numerical technique to automatically differentiate a code are first discussed, and then methodologies to apply the capabilities of the Institut National de Recherche en Informatique et en Automatique derivation tool to an industrial finite volume solver are discussed. Afterward, two examples of application to representative two-dimensional and three-dimensional test cases are shown and, for each one, comparisons are carried out between the results gathered using the automatic differentiation and the classical second-order finite difference technique for the evaluation of derivatives. Such comparison highlights the capability of automatic differentiation to produce reliable results even if applied to complex configurations and in very complex numerical structures. Finally, tradeoff considerations are made as a conclusio