Congenital Nystagmus eye movements analysis and oculomotor system models evaluation

The term Congenital Nystagmus (Early Onset Nystagmus or Infantile Nystagmus Syndrome) refers to a pathology characterised by an involuntary movement of the eyes, which often seriously reduces a subject’s vision. Congenital Nystagmus (CN) is a specific kind of nystagmus within the wider classification of infantile nystagmus, which can be best recognized and classified by means of a combination of clinical investigations and motility analysis; in some cases, eye movement recording and analysis are indispensable for diagnosis. However, interpretation of eye movement recordings still lacks of complete reliability; hence new analysis techniques and precise identification of concise parameters directly related to visual acuity are necessary to further support physicians’ decisions. To this aim, an index computed from eye movement recordings and related to the visual acuity of a subject is proposed in this thesis. This estimator is based on two parameters: the time spent by a subject effectively viewing a target (foveation time - Tf) and the standard deviation of eye position (SDp). Moreover, since previous studies have shown that visual acuity largely depends on SDp, a data collection pilot study was also conducted with the purpose of specifically identifying eventual slow rhythmic component in the eye position and to characterise in more detail the SDp. The results are presented in this thesis. In addition, some oculomotor system models are reviewed and a new approach to those models, i.e. the recovery of periodic orbits of the oculomotor system in patients with CN, is tested on real patients data. In conclusion, the results obtained within this research consent to completely and reliably characterise the slow rhythmic component sometimes present in eye position recordings of CN subjects and to better classify the different kinds of CN waveforms. Those findings can successfully support the clinicians in therapy planning and treatment outcome evaluation.

Foetal heart rate recording: analysis and comparison of different methodologies

Monitoring foetal health is a very important task in clinical practice to appropriately plan pregnancy management and delivery. In the third trimester of pregnancy, ultrasound cardiotocography is the most employed diagnostic technique: foetal heart rate and uterine contractions signals are simultaneously recorded and analysed in order to ascertain foetal health. Because ultrasound cardiotocography interpretation still lacks of complete reliability, new parameters and methods of interpretation, or alternative methodologies, are necessary to further support physicians’ decisions. To this aim, in this thesis, foetal phonocardiography and electrocardiography are considered as different techniques. Further, variability of foetal heart rate is thoroughly studied. Frequency components and their modifications can be analysed by applying a time-frequency approach, for a distinct understanding of the spectral components and their change over time related to foetal reactions to internal and external stimuli (such as uterine contractions). Such modifications of the power spectrum can be a sign of autonomic nervous system reactions and therefore represent additional, objective information about foetal reactivity and health. However, some limits of ultrasonic cardiotocography still remain, such as in long-term foetal surveillance, which is often recommendable mainly in risky pregnancies. In these cases, the fully non-invasive acoustic recording, foetal phonocardiography, through maternal abdomen, represents a valuable alternative to the ultrasonic cardiotocography. Unfortunately, the so recorded foetal heart sound signal is heavily loaded by noise, thus the determination of the foetal heart rate raises serious signal processing issues. A new algorithm for foetal heart rate estimation from foetal phonocardiographic recordings is presented in this thesis. Different filtering and enhancement techniques, to enhance the first foetal heart sounds, were applied, so that different signal processing techniques were implemented, evaluated and compared, by identifying the strategy characterized on average by the best results. In particular, phonocardiographic signals were recorded simultaneously to ultrasonic cardiotocographic signals in order to compare the two foetal heart rate series (the one estimated by the developed algorithm and the other provided by cardiotocographic device). The algorithm performances were tested on phonocardiographic signals recorded on pregnant women, showing reliable foetal heart rate signals, very close to the ultrasound cardiotocographic recordings, considered as reference. The algorithm was also tested by using a foetal phonocardiographic recording simulator developed and presented in this research thesis. The target was to provide a software for simulating recordings relative to different foetal conditions and recordings situations and to use it as a test tool for comparing and assessing different foetal heart rate extraction algorithms. Since there are few studies about foetal heart sounds time characteristics and frequency content and the available literature is poor and not rigorous in this area, a data collection pilot study was also conducted with the purpose of specifically characterising both foetal and maternal heart sounds. Finally, in this thesis, the use of foetal phonocardiographic and electrocardiographic methodology and their combination, are presented in order to detect foetal heart rate and other functioning anomalies. The developed methodologies, suitable for longer-term assessment, were able to detect heart beat events correctly, such as first and second heart sounds and QRS waves. The detection of such events provides reliable measures of foetal heart rate, potentially information about measurement of the systolic time intervals and foetus circulatory impedance.

A hybrid technology for parallel recording of single ion channels

Hybrid technologies, thanks to the convergence of integrated microelectronic devices and new class of microfluidic structures could open new perspectives to the way how nanoscale events are discovered, monitored and controlled. The key point of this thesis is to evaluate the impact of such an approach into applications of ion-channel High Throughput Screening (HTS)platforms. This approach offers promising opportunities for the development of new classes of sensitive, reliable and cheap sensors. There are numerous advantages of embedding microelectronic readout structures strictly coupled to sensing elements. On the one hand the signal-to-noise-ratio is increased as a result of scaling. On the other, the readout miniaturization allows organization of sensors into arrays, increasing the capability of the platform in terms of number of acquired data, as required in the HTS approach, to improve sensing accuracy and reliabiity. However, accurate interface design is required to establish efficient communication between ionic-based and electronic-based signals. The work made in this thesis will show a first example of a complete parallel readout system with single ion channel resolution, using a compact and scalable hybrid architecture suitable to be interfaced to large array of sensors, ensuring simultaneous signal recording and smart control of the signal-to-noise ratio and bandwidth trade off. More specifically, an array of microfluidic polymer structures, hosting artificial lipid bilayers blocks where single ion channel pores are embededed, is coupled with an array of ultra-low noise current amplifiers for signal amplification and data processing. As demonstrating working example, the platform was used to acquire ultra small currents derived by single non-covalent molecular binding between alpha-hemolysin pores and beta-cyclodextrin molecules in artificial lipid membranes.

Longitudinal evolution of cognitive functions in patients with multiple system atrophy: a prospective study

Introduction and Background: Multiple system atrophy (MSA) is a sporadic, adult-onset, progressive neurodegenerative disease characterized clinically by parkinsonism, cerebellar ataxia, and autonomic failure. We investigated cognitive functions longitudinally in a group of probable MSA patients, matching data with sleep parameters. Patients and Methods: 10 patients (7m/3f) underwent a detailed interview, a general and neurological examination, laboratory exams, MRI scans, a cardiovascular reflexes study, a battery of neuropsychological tests, and video-polysomnographic recording (VPSG). Patients were revaluated (T1) a mean of 16±5 (range: 12-28) months after the initial evaluation (T0). At T1, the neuropsychological assessment and VPSG were repeated. Results: The mean patient age was 57.8±6.4 years (range: 47-64) with a mean age at disease onset of 53.2±7.1 years (range: 43-61) and symptoms duration at T0 of 60±48 months (range: 12-144). At T0, 7 patients showed no cognitive deficits while 3 patients showed isolated cognitive deficits. At T1, 1 patient worsened developing multiple cognitive deficits from a normal condition. At T0 and T1, sleep efficiency was reduced, REM latency increased, NREM sleep stages 1-2 slightly increased. Comparisons between T1 and T0 showed a significant worsening in two tests of attention and no significant differences of VPSG parameters. No correlation was found between neuropsychological results and VPSG findings or RBD duration. Discussion and Conclusions: The majority of our patients do not show any cognitive deficits at T0 and T1, while isolated cognitive deficits are present in the remaining patients. Attention is the cognitive function which significantly worsened. Our data confirm the previous findings concerning the prevalence, type and the evolution of cognitive deficits in MSA. Regarding the developing of a condition of dementia, our data did not show a clear-cut diagnosis of dementia. We confirm a mild alteration of sleep structure. RBD duration does not correlate with neuropsychological findings.

Automatic risk evaluation in elderly patients based on Autonomic Nervous System assessment

Dysfunction of Autonomic Nervous System (ANS) is a typical feature of chronic heart failure and other cardiovascular disease. As a simple non-invasive technology, heart rate variability (HRV) analysis provides reliable information on autonomic modulation of heart rate. The aim of this thesis was to research and develop automatic methods based on ANS assessment for evaluation of risk in cardiac patients. Several features selection and machine learning algorithms have been combined to achieve the goals. Automatic assessment of disease severity in Congestive Heart Failure (CHF) patients: a completely automatic method, based on long-term HRV was proposed in order to automatically assess the severity of CHF, achieving a sensitivity rate of 93% and a specificity rate of 64% in discriminating severe versus mild patients. Automatic identification of hypertensive patients at high risk of vascular events: a completely automatic system was proposed in order to identify hypertensive patients at higher risk to develop vascular events in the 12 months following the electrocardiographic recordings, achieving a sensitivity rate of 71% and a specificity rate of 86% in identifying high-risk subjects among hypertensive patients. Automatic identification of hypertensive patients with history of fall: it was explored whether an automatic identification of fallers among hypertensive patients based on HRV was feasible. The results obtained in this thesis could have implications both in clinical practice and in clinical research. The system has been designed and developed in order to be clinically feasible. Moreover, since 5-minute ECG recording is inexpensive, easy to assess, and non-invasive, future research will focus on the clinical applicability of the system as a screening tool in non-specialized ambulatories, in order to identify high-risk patients to be shortlisted for more complex investigations.

Increasing Realism and Supporting Content Planning for Dynamic Scenes in a Mixed Reality System incorporating a Time-of-Flight Camera

For broadcasting purposes MIXED REALITY, the combination of real and virtual scene content, has become ubiquitous nowadays. Mixed Reality recording still requires expensive studio setups and is often limited to simple color keying. We present a system for Mixed Reality applications which uses depth keying and provides threedimensional mixing of real and artificial content. It features enhanced realism through automatic shadow computation which we consider a core issue to obtain realism and a convincing visual perception, besides the correct alignment of the two modalities and correct occlusion handling. Furthermore we present a possibility to support placement of virtual content in the scene. Core feature of our system is the incorporation of a TIME-OF-FLIGHT (TOF)-camera device. This device delivers real-time depth images of the environment at a reasonable resolution and quality. This camera is used to build a static environment model and it also allows correct handling of mutual occlusions between real and virtual content, shadow computation and enhanced content planning. The presented system is inexpensive, compact, mobile, flexible and provides convenient calibration procedures. Chroma-keying is replaced by depth-keying which is efficiently performed on the GRAPHICS PROCESSING UNIT (GPU) by the usage of an environment model and the current ToF-camera image. Automatic extraction and tracking of dynamic scene content is herewith performed and this information is used for planning and alignment of virtual content. An additional sustainable feature is that depth maps of the mixed content are available in real-time, which makes the approach suitable for future 3DTV productions. The presented paper gives an overview of the whole system approach including camera calibration, environment model generation, real-time keying and mixing of virtual and real content, shadowing for virtual content and dynamic object tracking for content planning.

Space-qualified laser system for the BepiColombo Laser Altimeter

The space-qualified design of a miniaturized laser for pulsed operation at a wavelength of 1064 nm and at repetition rates up to 10 Hz is presented. This laser consists of a pair of diode-laser pumped, actively q-switched Nd:YAG rod oscillators hermetically sealed and encapsulated in an environment of dry synthetic air. The system delivers at least 300 million laser pulses with 50 mJ energy and 5 ns pulse width (FWHM). It will be launched in 2017 aboard European Space Agency’s Mercury Planetary Orbiter as part of the BepiColombo Laser Altimeter, which, after a 6-years cruise, will start recording topographic data from orbital altitudes between 400 and 1500 km above Mercury’s surface.

An optimized lead system for long-term esophageal electrocardiography

Long-term electrocardiography (ECG) featuring adequate atrial and ventricular signal quality is highly desirable. Routinely used surface leads are limited in atrial signal sensitivity and recording capability impeding complete ECG delineation, i.e. in the presence of supraventricular arrhythmias. Long-term esophageal ECG might overcome these limitations but requires a dedicated lead system and recorder design. To this end, we analysed multiple-lead esophageal ECGs with respect to signal quality by describing the ECG waves as a function of the insertion level, interelectrode distance, electrode shape and amplifier's input range. The results derived from clinical data show that two bipolar esophageal leads, an atrial lead with short (15 mm) interelectrode distance and a ventricular lead with long (80 mm) interelectrode distance provide non-inferior ventricular signal strength and superior atrial signal strength compared to standard surface lead II. High atrial signal slope in particular is observed with the atrial esophageal lead. The proposed esophageal lead system in combination with an increased recorder input range of ±20 mV minimizes signal loss due to excessive electrode motion typically observed in esophageal ECGs. The design proposal might help to standardize long-term esophageal ECG registrations and facilitate novel ECG classification systems based on the independent detection of ventricular and atrial electrical activity.

Compact low-power cortical recording architecture for compressive multichannel data acquisition

This paper introduces an area- and power-efficient approach for compressive recording of cortical signals used in an implantable system prior to transmission. Recent research on compressive sensing has shown promising results for sub-Nyquist sampling of sparse biological signals. Still, any large-scale implementation of this technique faces critical issues caused by the increased hardware intensity. The cost of implementing compressive sensing in a multichannel system in terms of area usage can be significantly higher than a conventional data acquisition system without compression. To tackle this issue, a new multichannel compressive sensing scheme which exploits the spatial sparsity of the signals recorded from the electrodes of the sensor array is proposed. The analysis shows that using this method, the power efficiency is preserved to a great extent while the area overhead is significantly reduced resulting in an improved power-area product. The proposed circuit architecture is implemented in a UMC 0.18 [Formula: see text]m CMOS technology. Extensive performance analysis and design optimization has been done resulting in a low-noise, compact and power-efficient implementation. The results of simulations and subsequent reconstructions show the possibility of recovering fourfold compressed intracranial EEG signals with an SNR as high as 21.8 dB, while consuming 10.5 [Formula: see text]W of power within an effective area of 250 [Formula: see text]m × 250 [Formula: see text]m per channel.

A Baseline Wander Tracking System for Artifact Rejection in Long-Term Electrocardiography

Long-term electrocardiogram (ECG) signals might suffer from relevant baseline disturbances during physical activity. Motion artifacts in particular are more pronounced with dry surface or esophageal electrodes which are dedicated to prolonged ECG recording. In this paper we present a method called baseline wander tracking (BWT) that tracks and rejects strong baseline disturbances and avoids concurrent saturation of the analog front-end. The proposed algorithm shifts the baseline level of the ECG signal to the middle of the dynamic input range. Due to the fast offset shifts, that produce much steeper signal portions than the normal ECG waves, the true ECG signal can be reconstructed offline and filtered using computationally intensive algorithms. Based on Monte Carlo simulations we observed reconstruction errors mainly caused by the non-linearity inaccuracies of the DAC. However, the signal to error ratio of the BWT is higher compared to an analog front-end featuring a dynamic input ranges above 15 mV if a synthetic ECG signal was used. The BWT is additionally able to suppress (electrode) offset potentials without introducing long transients. Due to its structural simplicity, memory efficiency and the DC coupling capability, the BWT is dedicated to high integration required in long-term and low-power ECG recording systems.

Geometry and kinematics of the Roisan-Cignana Shear Zone, and the orogenic evolution of the Dent Blanche Tectonic System (Western Alps)

The Dent Blanche Tectonic System (DBTS) is a composite thrust sheet derived from the previously thinned passive Adriatic continental margin. A kilometric high-strain zone, the Roisan-Cignana Shear Zone (RCSZ) defines the major tectonic boundary within the DBTS and separates it into two subunits, the Dent Blanche s.s. nappe to the northwest and the Mont Mary nappe to the southeast. Within this shear zone, tectonic slices of Mesozoic and pre-Alpine meta-sediments became amalgamated with continental basement rocks of the Adriatic margin. The occurrence of high pressure assemblages along the contact between these tectonic slices indicates that the amalgamation occurred prior to or during the subduction process, at an early stage of the Alpine orogenic cycle. Detailed mapping, petrographic and structural analysis show that the Roisan-Cignana Shear Zone results from several superimposed Alpine structural and metamorphic stages. Subduction of the continental fragments is recorded by blueschist-facies deformation, whereas the Alpine collision is reflected by a greenschist facies overprint associated with the development of large-scale open folds. The postnappe evolution comprises the development of low-angle brittle faults, followed by large-scale folding (Vanzone phase) and finally brittle extensional faults. The RCSZ shows that fragments of continental crust had been torn off the passive continental margin prior to continental collision, thus recording the entire history of the orogenic cycle. The role of preceding Permo-Triassic lithospheric thinning, Jurassic rifting, and ablative subduction processes in controlling the removal of crustal fragments from the reactivated passive continental margin is discussed. Results of this study constrain the temporal sequence of the tectono-metamorphic processes involved in the assembly of the DBTS, but they also show limits on the interpretation. In particular it remains difficult to judge to what extent precollisional rifting at the Adriatic continental margin preconditioned the efficiency of convergent processes, i.e. accretion, subduction, and orogenic exhumation.

APPLICATION OF THE BRAINSTEM EVOKED RESPONSE (BER) TO NEUROTOXICITY EVALUATION OF THE AUDITORY SYSTEM: ASSESSMENT OF INORGANIC LEAD-INDUCED OTOTOXICITY

An experimental procedure was developed using the Brainstem Evoked Response (BER) electrophysiological technique to assess the effect of neurotoxic substances on the auditory system. The procedure utilizes Sprague-Dawley albino rats who have had dural electrodes implanted in their skulls, allowing neuroelectric evoked potentials to be recorded from their brainstems. Latency and amplitude parameters derived from the evoked potentials help assess the neuroanatomical integrity of the auditory pathway in the brainstem. Moreover, since frequency-specific auditory stimuli are used to evoke the neural responses, additional audiometric information is obtainable. An investigation on non-exposed control animals shows the BER threshold curve obtained by tests at various frequencies very closely approximates that obtained by behavioral audibility tests. Thus, the BER appears to be a valid measure of both functional and neuroanatomical integrity of the afferent auditory neural pathway.^ To determine the usefulness of the BER technique in neurobehavioral toxicology research, a known neurotoxic agent, Pb, was studied. Female Sprague-Dawley rats were dosed for 45 days with low levels of Pb acetate in their drinking water, after which BER recordings were obtained. The Pb dosages were determined from the findings of an earlier pilot study. One group of 6 rats received normal tap water, one group of 7 rats received a solution of 0.1% Pb, and another group of 7 rats received a solution of 0.2% Pb. After 45 days, the three groups exhibited blood Pb levels of 4.5 (+OR-) 0.43 (mu)g/100 ml, 37.8 (+OR-) 4.8 (mu)g/100 ml and 47.3 (+OR-) 2.7 (mu)g/100 ml, respectively.^ The results of the BER recording indicated evoked response waveform latency abnormalities in both the Pb-treated groups when midrange frequency (8 kHz to 32 kHz) stimuli were used. For the most part, waveform amplitudes did not vary significantly from control values. BER recordings obtained after a 30-day recovery period indicated the effects seen in the 0.1% Pb group had disappeared. However, those anomalies exhibited by the 0.2% Pb group either remained or increased in number. This outcome indicates a longer lasting or possibly irreversible effect on the auditory system from the higher dose of Pb. The auditory pathway effect appears to be in the periphery, at the level of the cochlea or the auditory (VIII) nerve. The results of this research indicate the BER technique is a valuable and sensitive indicator of low-level toxic effects on the auditory system.^

A Multi-Agent System for the Solution of Fuzzy Incidents in Telecommunications

This article presents a multi-agent expert system (SMAF) , that allows the input of incidents which occur in different elements of the telecommunications area. SMAF interacts with experts and general users, and each agent with all the agents? community, recording the incidents and their solutions in a knowledge base, without the analysis of their causes. The incidents are expressed using keywords taken from natural language (originally Spanish) and their main concepts are recorded with their severities as the users express them. Then, there is a search of the best solution for each incident, being helped by a human operator using a distancenotions between them.

Multi-microphone recordings (EigenMike32) inside a WFS system (Iosono) through Ambisonics techniques using Matlab

El audio multicanal ha avanzado a pasos agigantados en los últimos años, y no solo en las técnicas de reproducción, sino que en las de capitación también. Por eso en este proyecto se encuentran ambas cosas: un array microfónico, EigenMike32 de MH Acoustics, y un sistema de reproducción con tecnología Wave Field Synthesis, instalado Iosono en la Jade Höchscule Oldenburg. Para enlazar estos dos puntos de la cadena de audio se proponen dos tipos distintos de codificación: la reproducción de la toma horizontal del EigenMike32; y el 3er orden de Ambisonics (High Order Ambisonics, HOA), una técnica de codificación basada en Armónicos Esféricos mediante la cual se simula el campo acústico en vez de simular las distintas fuentes. Ambas se desarrollaron en el entorno Matlab y apoyadas por la colección de scripts de Isophonics llamada Spatial Audio Matlab Toolbox. Para probar éstas se llevaron a cabo una serie de test en los que se las comparó con las grabaciones realizadas a la vez con un Dummy Head, a la que se supone el método más aproximado a nuestro modo de escucha. Estas pruebas incluían otras grabaciones hechas con un Doble MS de Schoeps que se explican en el proyecto “Sally”. La forma de realizar éstas fue, una batería de 4 audios repetida 4 veces para cada una de las situaciones garbadas (una conversación, una clase, una calle y un comedor universitario). Los resultados fueron inesperados, ya que la codificación del tercer orden de HOA quedo por debajo de la valoración Buena, posiblemente debido a la introducción de material hecho para un array tridimensional dentro de uno de 2 dimensiones. Por el otro lado, la codificación que consistía en extraer los micrófonos del plano horizontal se mantuvo en el nivel de Buena en todas las situaciones. Se concluye que HOA debe seguir siendo probado con mayores conocimientos sobre Armónicos Esféricos; mientras que el otro codificador, mucho más sencillo, puede ser usado para situaciones sin mucha complejidad en cuanto a espacialidad. In the last years the multichannel audio has increased in leaps and bounds and not only in the playback techniques, but also in the recording ones. That is the reason of both things being in this project: a microphone array, EigenMike32 from MH Acoustics; and a playback system with Wave Field Synthesis technology, installed by Iosono in Jade Höchscule Oldenburg. To link these two points of the audio chain, 2 different kinds of codification are proposed: the reproduction of the EigenMike32´s horizontal take, and the Ambisonics´ third order (High Order Ambisonics, HOA), a codification technique based in Spherical Harmonics through which the acoustic field is simulated instead of the different sound sources. Both have been developed inside Matlab´s environment and supported by the Isophonics´ scripts collection called Spatial Audio Matlab Toolbox. To test these, a serial of tests were made in which they were compared with recordings made at the time by a Dummy Head, which is supposed to be the closest method to our hearing way. These tests included other recording and codifications made by a Double MS (DMS) from Schoeps which are explained in the project named “3D audio rendering through Ambisonics techniques: from multi-microphone recordings (DMS Schoeps) to a WFS system, through Matlab”. The way to perform the tests was, a collection made of 4 audios repeated 4 times for each recorded situation (a chat, a class, a street and college canteen or Mensa). The results were unexpected, because the HOA´s third order stood under the Well valuation, possibly caused by introducing material made for a tridimensional array inside one made only by 2 dimensions. On the other hand, the codification that consisted of extracting the horizontal plane microphones kept the Well valuation in all the situations. It is concluded that HOA should keep being tested with larger knowledge about Spherical Harmonics; while the other coder, quite simpler, can be used for situations without a lot of complexity with regards to spatiality.

A Multingual Web-based Educational System for Professional Musicians

This paper presents the main results of the eContent HARMOS project. The project has developed a webbased educational system for professional musicians. The main idea of the project consists of recording master classes taught by highly recognised maestros and annotate this multimedia material using an educational musical taxonomy and automatic annotation tools. Users of the system access a multi-criteria search engine that allows them to find and play video segments according to a combination of criteria, which include instrument, teacher, composer, composition, movement and pedagogical concept. In order to preserve teachers and students rights, a DRM and protection system has been developed. The system is being publicly exploited. This model preserves musical heritage, since these valuable master classes are usually not recorded and it also provides a sustainable model for musical institutions.