P300-Based Brain–Computer Interface Communication: Evaluation and Follow-up in Amyotrophic Lateral Sclerosis

To describe results of training and 1-year follow-up of brain-communication in a larger group of early and middle stage amyotrophic lateral sclerosis (ALS) patients using a P300-based brain–computer interface (BCI), and to investigate the relationship between clinical status, age and BCI performance. A group of 21 ALS patients were tested with a BCI-system using two-dimensional cursor movements. A four choice visual paradigm was employed to training and test the brain-communication abilities. The task consisted of reaching with the cursor one out of four icons representing four basic needs. Five patients performed a follow-up test 1 year later. The clinical severity in all patients were assessed with a battery of clinical tests. A comparable control group of nine healthy subjects was employed to investigate performance differences. Nineteen patients and nine healthy subjects were able to achieve good and excellent cursor movements' control, acquiring at least communication abilities above chance level; during follow-up the patients maintained their BCI-skill. We found mild cognitive impairments in the ALS group which may be attributed to motor deficiencies, while no relevant correlation has been found between clinical data and BCI performance. A positive correlation between age and the BCI-skill in patients was found. Time since training acquisition and clinical status did not affect the patients brain-communication skill at early and middle stage of the disease. A brain-communication tool can be used in most ALS patients at early and middle stage of the disease before entering the locked-in stage

RETRACE-3D PROJECT, a multidisciplinary approach for the construction of a 3D crustal model: first results and seismotectonic implications

The RETRACE-3D (centRal italy EarThquakes integRAted Crustal modEl) Project has been launched with the ambitious goal to build, as first result, a new, robust, 3D geological model of broad consensus of the area struck by the 2016-2018 Central Italy seismic sequencePublishedBologna3T. Sorgente sismica4T. Sismicità dell'Itali

High shear wet granulation: process understanding and scale up

Among all the powder agglomeration processes, high shear wet granulation is one of the most commonly used techniques. It consists of the agglomeration of different powders through the addition of a granulating fluid and a vigorous mixing. Industries often turn to high shear granulation mainly to avoid segregation of critical components in a powder mixture, improve flowability and compactibility. Despite the great importance of this technique in many industrial activities, it is not totally clear how changes in the initial powder mixture or in process variables can affect the final product properties. Moreover, scale-up of high shear granulators is still difficult to perform. The present research mainly focuses on the high shear wet granulation of pharmaceutical powders. Particularly, this research aims at closing the gap in understanding the role of primary particle properties (e.g. composition, primary particle size distribution) and process parameters (e.g. mixing speed, liquid flow rate and amount) on the final granule characteristics. Scale-up effects on the powder flow patterns were investigated as well.Tra tutti i processi di agglomerazione di polveri, la granulazione ad elevato shear risulta essere una delle tecniche più usate. Questa tecnica consiste nell‘agglomerazione di diverse polveri dovuta all‘aggiunta di un liquido legante e a un mescolamento energico. La granulazione ad elevato shear è utilizzata principalmente per evitare la segregazione di componenti critici in una miscela di polveri, per migliorare la scorrevolezza e comprimibilità. Nonostante l‘importanza di questa tecnica in numerosi settori industriali, l‘effetto delle proprietà delle polveri e dei parametri di processo sul prodotto finale è ancora poco chiaro. Lo scale up dei granulatori ad elevato shear risulta inoltre ancora difficile da portare a termine. La presente ricerca riguarda la granulazione high shear di polveri farmaceutiche. Lo scopo della ricerca è approfondire la conoscenza sul ruolo delle proprietà delle particelle nella miscela iniziale (p.e. composizione e distribuzione granulometrica) e parametri di processo (p.e. velocità di agitazione, portata e quantità di liquido) nel determinare le caratteristiche del prodotto finale. È stato inoltre analizzato l‘effetto dello scale up sul regime di mescolamento

formulation design and experiment interpretation through torque measurements in high shear wet granulation

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Formulation design and experiment interpretation through torque measurements in high-shear wet granulation

High-shear wet granulation is commonly used in many industries such as in the pharmaceutical one to convert fine cohesive powders into dense and round granules. The purpose of this work was to determine the effects of some important powder properties (crystalline or amorphous nature, hygroscopicity, solubility and particle size) and process variables (liquid addition rate, impeller speed) on the early stages of the granulation process and on drug distribution in granules obtained by high shear wet granulation. The glass transition concept coupled with on-line impeller torque monitoring and measurements of the time evolution of the particle size distribution were used to study mixtures of pharmaceutical excipients and some common active ingredients. In particular a formulation map for estimating the minimum amount of liquid binder required to induce appreciable granule growth is presented outlining therefore a new method to considerably increase the predictability of the behaviour of different formulations on the basis of the physical properties of each single component. The description of the effects of wetting condition on drug uniformity content in some formulation with hydrophobic actives is given as well

Scale-up effects on flow patterns in the high shear mixing of cohesive powders

Processing of granular material often requires mixing steps in order to blend cohesive powders, distribute viscous liquids into powder beds or create agglomerates from a wet powder mass. For this reason, using bladed, high-speed mixers is frequently considered a good solution by many types of industry. However, despite the importance of such mixers in powder processing, the granular flow behavior inside the mixer bowl is generally not totally understood. In this work extensive experimentation was performed comparing the behavior of a lab-scale mixer (1.9. l vessel volume) to that of a pilot-scale mixer (65. l vessel volume) with a mixture of some pharmaceutical excipients (e.g. lactose, cellulose). The aim was to propose a new and more detailed method for describing the complex powder rheology inside an high shear mixer using impeller torque, current consumption and particle image velocimetry (PIV) analysis. Particularly, a new dimensionless torque number is proposed for the torque profile analysis in order to isolate the contributions of mass fill and blade clearance at the vessel base. Impeller torque and motor current consumption were integrated with PIV to obtain more detailed information about the surface velocity and flow pattern changes in the pilot-scale mixer. Mass fill resulted to be one of the most critical variables, as predicted by the torque model, strongly affecting the powder flow patterns. An additional mixing regimes was furthermore defined according to the observation of the surface velocity of the powder bed